ENERGY

In physics, energy (Ancient Greek: ἐνέργεια energeia "activity, operation"[1]) is an

indirectly observed quantity. It is often understood as the ability a physical system
has to do work on other physical systems.[2][3] Since work is defined as a force
acting through a distance (a length of space), energy is always equivalent to the
ability to exert pulls or pushes against the basic forces of nature, along a path of a
certain length.

The total energy contained in an object is identified with its mass, and energy (like
mass), cannot be created or destroyed. When matter (ordinary material particles) is
changed into energy (such as energy of motion, or into radiation), the mass of the
system does not change through the transformation process. However, there may
be mechanistic limits as to how much of the matter in an object may be changed
into other types of energy and thus into work, on other systems. Energy, like mass,
is a scalar physical quantity. In the International System of Units (SI), energy is
measured in joules, but in many fields other units, such as kilowatt-hours and
kilocalories, are customary. All of these units translate to units of work, which is
always defined in terms of forces and the distances that the forces act through.

A system can transfer energy to another system by simply transferring matter to it

(since matter is equivalent to energy, in accordance with its mass). However, when
energy is transferred by means other than matter-transfer, the transfer produces
changes in the second system, as a result of work done on it. This work manifests
itself as the effect of force(s) applied through distances within the target system.
For example, a system can emit energy to another by transferring (radiating)
electromagnetic energy, but this creates forces upon the particles that absorb the
radiation. Similarly, a system may transfer energy to another by physically
impacting it, but that case the energy of motion in an object, called kinetic energy,
results in forces acting over distances (new energy) to appear in another object that
is struck. Transfer of thermal energy by heat occurs by both of these mechanisms:
heat can be transferred by electromagnetic radiation, or by physical contact in
which direct particle-particle impacts transfer kinetic energy.

Energy may be stored in systems without being present as matter, or as kinetic or

electromagnetic energy. Stored energy is created whenever a particle has been
moved through a field it interacts with (requiring a force to do so), but the energy
to accomplish this is stored as a new position of the particles in the field—a
configuration that must be "held" or fixed by a different type of force (otherwise,
the new configuration would resolve itself by the field pushing or pulling the
particle back toward its previous position). This type of energy "stored" by force-
fields and particles that have been forced into a new physical configuration in the
field by doing work on them by another system, is referred to as potential energy.
A simple example of potential energy is the work needed to lift an object in a
gravity field, up to a support. Each of the basic forces of nature is associated with a
different type of potential energy, and all types of potential energy (like all other
types of energy) appears as system mass, whenever present. For example, a
compressed spring will be slightly more massive than before it was compressed.
Likewise, whenever energy is transferred between systems by any mechanism, an
associated mass is transferred with it.

Any form of energy may be transformed into another form. For example, all types
of potential energy are converted into kinetic energy when the objects are given
freedom to move to different position (as for example, when an object falls off a
support). When energy is in a form other than thermal energy, it may be
transformed with good or even perfect efficiency, to any other type of energy,
including electricity or production of new particles of matter. With thermal energy,
however, there are often limits to the efficiency of the conversion to other forms of
energy, as described by the second law of thermodynamics.

In all such energy transformation processes, the total energy remains the same, and
a transfer of energy from one system to another, results in a loss to compensate for
any gain. This principle, the conservation of energy, was first postulated in the
early 19th century, and applies to any isolated system. According to Noether's
theorem, the conservation of energy is a consequence of the fact that the laws of
physics do not change over time.[4]

Although the total energy of a system does not change with time, its value may
depend on the frame of reference. For example, a seated passenger in a moving
airplane has zero kinetic energy relative to the airplane, but non-zero kinetic
energy (and higher total energy) relative to the Earth.

In physics, energy (Ancient Greek: ἐνέργεια energeia "activity, operation"[1]) is an

indirectly observed quantity. It is often understood as the ability a physical system
has to do work on other physical systems.[2][3] Since work is defined as a force
acting through a distance (a length of space), energy is always equivalent to the
ability to exert pulls or pushes against the basic forces of nature, along a path of a
certain length.
The total energy contained in an object is identified with its mass, and energy (like
mass), cannot be created or destroyed. When matter (ordinary material particles) is
changed into energy (such as energy of motion, or into radiation), the mass of the
system does not change through the transformation process. However, there may
be mechanistic limits as to how much of the matter in an object may be changed
into other types of energy and thus into work, on other systems. Energy, like mass,
is a scalar physical quantity. In the International System of Units (SI), energy is
measured in joules, but in many fields other units, such as kilowatt-hours and
kilocalories, are customary. All of these units translate to units of work, which is
always defined in terms of forces and the distances that the forces act through.

A system can transfer energy to another system by simply transferring matter to it

(since matter is equivalent to energy, in accordance with its mass). However, when
energy is transferred by means other than matter-transfer, the transfer produces
changes in the second system, as a result of work done on it. This work manifests
itself as the effect of force(s) applied through distances within the target system.
For example, a system can emit energy to another by transferring (radiating)
electromagnetic energy, but this creates forces upon the particles that absorb the
radiation. Similarly, a system may transfer energy to another by physically
impacting it, but that case the energy of motion in an object, called kinetic energy,
results in forces acting over distances (new energy) to appear in another object that
is struck. Transfer of thermal energy by heat occurs by both of these mechanisms:
heat can be transferred by electromagnetic radiation, or by physical contact in
which direct particle-particle impacts transfer kinetic energy.

Energy may be stored in systems without being present as matter, or as kinetic or

electromagnetic energy. Stored energy is created whenever a particle has been
moved through a field it interacts with (requiring a force to do so), but the energy
to accomplish this is stored as a new position of the particles in the field—a
configuration that must be "held" or fixed by a different type of force (otherwise,
the new configuration would resolve itself by the field pushing or pulling the
particle back toward its previous position). This type of energy "stored" by force-
fields and particles that have been forced into a new physical configuration in the
field by doing work on them by another system, is referred to as potential energy.
A simple example of potential energy is the work needed to lift an object in a
gravity field, up to a support. Each of the basic forces of nature is associated with a
different type of potential energy, and all types of potential energy (like all other
types of energy) appears as system mass, whenever present. For example, a
compressed spring will be slightly more massive than before it was compressed.
Likewise, whenever energy is transferred between systems by any mechanism, an
associated mass is transferred with it.

Any form of energy may be transformed into another form. For example, all types
of potential energy are converted into kinetic energy when the objects are given
freedom to move to different position (as for example, when an object falls off a
support). When energy is in a form other than thermal energy, it may be
transformed with good or even perfect efficiency, to any other type of energy,
including electricity or production of new particles of matter. With thermal energy,
however, there are often limits to the efficiency of the conversion to other forms of
energy, as described by the second law of thermodynamics.

In all such energy transformation processes, the total energy remains the same, and
a transfer of energy from one system to another, results in a loss to compensate for
any gain. This principle, the conservation of energy, was first postulated in the
early 19th century, and applies to any isolated system. According to Noether's
theorem, the conservation of energy is a consequence of the fact that the laws of
physics do not change over time.[4]

Although the total energy of a system does not change with time, its value may
depend on the frame of reference. For example, a seated passenger in a moving
airplane has zero kinetic energy relative to the airplane, but non-zero kinetic
energy (and higher total energy) relative to the Earth.

Definition: Energy is the capacity of a physical system to perform work. Energy

exists in several forms such as heat, kinetic or mechanical energy, light, potential
energy, electrical, or other forms.

Energy is a term of physics which describes something that we can not hold or
see.

Energy is the ability to do work or to cause change.

OR

Energy is the capacity of a physical system to perform work.

Adenosine-5'-triphosphate (ATP) is a multifunctional nucleotide
used in cells as a coenzyme. It is often called the "molecular unit of currency" of
intracellular energy transfer.[1] ATP transports chemical energy within cells for
metabolism. It is produced by photosphorylation and cellular respiration and used
by enzymes and structural proteins in many cellular processes, including
biosynthetic reactions, motility, and cell division.[2] One molecule of ATP contains
three phosphate groups, and it is produced by ATP synthase from inorganic
phosphate and adenosine diphosphate (ADP) or adenosine monophosphate (AMP).

Metabolic processes that use ATP as an energy source convert it back into its
precursors. ATP is therefore continuously recycled in organisms: the human body,
which on average contains only 250 grams (8.8 oz) of ATP,[3] turns over its own
body weight in ATP each day.[4]

ATP is used as a substrate in signal transduction pathways by kinases that

phosphorylate proteins and lipids, as well as by adenylate cyclase, which uses ATP
to produce the second messenger molecule cyclic AMP. The ratio between ATP
and AMP is used as a way for a cell to sense how much energy is available and
control the metabolic pathways that produce and consume ATP.[5] Apart from its
roles in energy metabolism and signaling, ATP is also incorporated into nucleic
acids by polymerases in the processes of DNA replication and transcription.

The structure of this molecule consists of a purine base (adenine) attached to the 1'
carbon atom of a pentose sugar (ribose). Three phosphate groups are attached at
the 5' carbon atom of the pentose sugar. It is the addition and removal of these
phosphate groups that inter-convert ATP, ADP and AMP. When ATP is used in
DNA synthesis, the ribose sugar is first converted to deoxyribose by ribonucleotide
reductase.

ATP was discovered in 1929 by Karl Lohmann,[6] but its correct structure was not
determined until some years later. It was proposed to be the main energy-transfer
molecule in the cell by Fritz Albert Lipmann in 1941.[7] It was first artificially
synthesized by Alexander Todd in 1948.[8]

ATP consists of adenosine — composed of an adenine ring and a ribose sugar —

and three phosphate groups (triphosphate). The phosphoryl groups, starting with
the group closest to the ribose, are referred to as the alpha (α), beta (β), and gamma
(γ) phosphates. Consequently, as a nucleotide, it (and its relatives ADP and AMP)
is basically a monomer of RNA. ATP is highly soluble in water and is quite stable
in solutions between pH 6.8–7.4, but is rapidly hydrolysed at extreme pH.
Consequently, ATP is best stored as an anhydrous salt.[9]

ATP is an unstable molecule in unbuffered water, in which it hydrolyses to ADP

and phosphate. This is because the strength of the bonds between the phosphate
groups in ATP are less than the strength of the hydrogen bonds (hydration bonds),
between its products (ADP + phosphate), and water. Thus, if ATP and ADP are in
chemical equilibrium in water, almost all of the ATP will eventually be converted
to ADP. A system that is far from equilibrium contains Gibbs free energy, and is
capable of doing work. Living cells maintain the ratio of ATP to ADP at a point
ten orders of magnitude from equilibrium, with ATP concentrations a thousandfold
higher than the concentration of ADP. This displacement from equilibrium means
that the hydrolysis of ATP in the cell releases a large amount of free energy.[10]

Two high-energy phosphate bonds (phosphoanhydride bonds) (those that connect

adjacent phosphates) in an ATP molecule are responsible for the high energy
content of this molecule.[11] In the context of biochemical reactions, these
anhydride bonds are frequently—and sometimes controversially—referred to as
high-energy bonds.[12] Energy stored in ATP may be released upon hydrolysis of
the anhydride bonds.[11] The bonds formed after hydrolysis—or the
phosphorylation of a residue by ATP—are lower in energy than the
phosphoanhydride bonds of ATP. During enzyme-catalyzed hydrolysis of ATP or
phosphorylation by ATP, the available free energy can be harnessed by a living
system to do work.[13][14]

Any unstable system of potentially reactive molecules could potentially serve as a

way of storing free energy, if the cell maintained their concentration far from the
equilibrium point of the reaction.[10] However, as is the case with most polymeric
biomolecules, the breakdown of RNA, DNA, and ATP into simpler monomers is
driven by both energy-release and entropy-increase considerations, in both
standard concentrations, and also those concentrations encountered within the cell.

The standard amount of energy released from hydrolysis of ATP can be calculated
from the changes in energy under non-natural (standard) conditions, then
correcting to biological concentrations. The net change in heat energy (enthalpy) at
standard temperature and pressure of the decomposition of ATP into hydrated ADP
and hydrated inorganic phosphate is −20.5 kJ/mol, with a change in free energy of
3.4 kJ/mol.[15] The energy released by cleaving either a phosphate (Pi) or
pyrophosphate (PPi) unit from ATP at standard state of 1 M are:[16]

ATP + H2O → ADP + Pi ΔG˚ = −30.5 kJ/mol (−7.3 kcal/mol)

ATP + H2O → AMP + PPi ΔG˚ = −45.6 kJ/mol (−10.9 kcal/mol)

These values can be used to calculate the change in energy under physiological
conditions and the cellular ATP/ADP ratio. However, a more representative value
(which takes AMP into consideration) called the Energy charge is increasingly
being employed. The values given for the Gibbs free energy for this reaction are
dependent on a number of factors, including overall ionic strength and the presence
of alkaline earth metal ions such as Mg2+ and Ca2+. Under typical cellular
conditions, ΔG is approximately −57 kJ/mol (−14 kcal/mol).[17]

[edit] Ionization in biological systems

ATP has multiple ionizable groups with different acid dissociation constants. In
neutral solution, ATP is ionized and exists mostly as ATP4−, with a small
proportion of ATP3−.[18] As ATP has several negatively charged groups in neutral
solution, it can chelate metals with very high affinity. The binding constant for
various metal ions are (given as per mole) as Mg2+ (9 554), Na+ (13), Ca2+ (3 722),
K+ (8), Sr2+ (1 381) and Li+ (25).[19] Due to the strength of these interactions, ATP
exists in the cell mostly in a complex with Mg2+.[18][20]

[edit] Biosynthesis

The ATP concentration inside the cell is typically 1–10 mM.[21] ATP can be
produced by redox reactions using simple and complex sugars (carbohydrates) or
lipids as an energy source. For ATP to be synthesized from complex fuels, they
first need to be broken down into their basic components. Carbohydrates are
hydrolysed into simple sugars, such as glucose and fructose. Fats (triglycerides) are
metabolised to give fatty acids and glycerol.

The overall process of oxidizing glucose to carbon dioxide is known as cellular

respiration and can produce about 30 molecules of ATP from a single molecule of
glucose.[22] ATP can be produced by a number of distinct cellular processes; the
three main pathways used to generate energy in eukaryotic organisms are
glycolysis and the citric acid cycle/oxidative phosphorylation, both components of
cellular respiration; and beta-oxidation. The majority of this ATP production by a
non-photosynthetic aerobic eukaryote takes place in the mitochondria, which can
make up nearly 25% of the total volume of a typical cell.[23]
[edit] Glycolysis

Main article: glycolysis

In glycolysis, glucose and glycerol are metabolized to pyruvate via the glycolytic
pathway. In most organisms, this process occurs in the cytosol, but, in some
protozoa such as the kinetoplastids, this is carried out in a specialized organelle
called the glycosome.[24] Glycolysis generates a net two molecules of ATP through
substrate phosphorylation catalyzed by two enzymes: PGK and pyruvate kinase.
Two molecules of NADH are also produced, which can be oxidized via the
electron transport chain and result in the generation of additional ATP by ATP
synthase. The pyruvate generated as an end-product of glycolysis is a substrate for
the Krebs Cycle.[25]

[edit] Glucose

Main articles: Citric acid cycle and oxidative phosphorylation

In the mitochondrion, pyruvate is oxidized by the pyruvate dehydrogenase

complex to Acetyl group, which is fully oxidized to carbon dioxide by the citric
acid cycle (also known as the Krebs Cycle). Every "turn" of the citric acid cycle
produces two molecules of carbon dioxide, one molecule of the ATP equivalent
guanosine triphosphate (GTP) through substrate-level phosphorylation catalyzed
by succinyl-CoA synthetase, three molecules of the reduced coenzyme NADH, and
one molecule of the reduced coenzyme FADH2. Both of these latter molecules are
recycled to their oxidized states (NAD+ and FAD, respectively) via the electron
transport chain, which generates additional ATP by oxidative phosphorylation. The
oxidation of an NADH molecule results in the synthesis of between 2-3 ATP
molecules, and the oxidation of one FADH2 yields between 1-2 ATP molecules.[22]
The majority of cellular ATP is generated by this process. Although the citric acid
cycle itself does not involve molecular oxygen, it is an obligately aerobic process
because O2 is needed to recycle the reduced NADH and FADH2 to their oxidized
states. In the absence of oxygen the citric acid cycle will cease to function due to
the lack of available NAD+ and FAD.[23]

The generation of ATP by the mitochondrion from cytosolic NADH relies on the
malate-aspartate shuttle (and to a lesser extent, the glycerol-phosphate shuttle)
because the inner mitochondrial membrane is impermeable to NADH and NAD+.
Instead of transferring the generated NADH, a malate dehydrogenase enzyme
converts oxaloacetate to malate, which is translocated to the mitochondrial matrix.
Another malate dehydrogenase-catalyzed reaction occurs in the opposite direction,
producing oxaloacetate and NADH from the newly transported malate and the
mitochondrion's interior store of NAD+. A transaminase converts the oxaloacetate
to aspartate for transport back across the membrane and into the intermembrane
space.[23]

In oxidative phosphorylation, the passage of electrons from NADH and FADH2

through the electron transport chain powers the pumping of protons out of the
mitochondrial matrix and into the intermembrane space. This creates a proton
motive force that is the net effect of a pH gradient and an electric potential gradient
across the inner mitochondrial membrane. Flow of protons down this potential
gradient — that is, from the intermembrane space to the matrix — provides the
driving force for ATP synthesis by ATP synthase. This enzyme contains a rotor
subunit that physically rotates relative to the static portions of the protein during
ATP synthesis.[26]

Most of the ATP synthesized in the mitochondria will be used for cellular
processes in the cytosol; thus it must be exported from its site of synthesis in the
mitochondrial matrix. The inner membrane contains an antiporter, the ADP/ATP
translocase, which is an integral membrane protein used to exchange newly-
synthesized ATP in the matrix for ADP in the intermembrane space.[27] This
translocase is driven by the membrane potential, as it results in the movement of
about 4 negative charges out of the mitochondrial membrane in exchange for 3
negative charges moved inside. However, it is also necessary to transport
phosphate into the mitochondrion; the phosphate carrier moves a proton in with
each phosphate, partially dissipating the proton gradient.

[edit] Beta oxidation

Main article: beta-oxidation

Fatty acids can also be broken down to acetyl-CoA by beta-oxidation. Each round
of this cycle reduces the length of the acyl chain by two carbon atoms and
produces one NADH and one FADH2 molecule, which are used to generate ATP
by oxidative phosphorylation. Because NADH and FADH2 are energy-rich
molecules, dozens of ATP molecules can be generated by the beta-oxidation of a
single long acyl chain. The high energy yield of this process and the compact
storage of fat explain why it is the most dense source of dietary calories.[28]

[edit] Anaerobic respiration

Main article: anaerobic respiration

Anaerobic respiration or fermentation entails the generation of energy via the
process of oxidation in the absence of O2 as an electron acceptor. In most
eukaryotes, glucose is used as both an energy store and an electron donor. The
equation for the oxidation of glucose to lactic acid is:

C6H12O6 2CH3CH(OH)COOH + 2 ATP

In prokaryotes, multiple electron acceptors can be used in anaerobic respiration.

These include nitrate, sulfate or carbon dioxide. These processes lead to the
ecologically-important processes of denitrification, sulfate reduction and
acetogenesis, respectively.[29][30]

[edit] ATP replenishment by nucleoside diphosphate kinases

ATP can also be synthesized through several so-called "replenishment" reactions

catalyzed by the enzyme families of nucleoside diphosphate kinases (NDKs),
which use other nucleoside triphosphates as a high-energy phosphate donor, and
the ATP:guanido-phosphotransferase family,

[edit] ATP production during photosynthesis

In plants, ATP is synthesized in thylakoid membrane of the chloroplast during the

light-dependent reactions of photosynthesis in a process called
photophosphorylation. Here, light energy is used to pump protons across the
chloroplast membrane. This produces a proton-motive force and this drives the
ATP synthase, exactly as in oxidative phosphorylation.[31] Some of the ATP
produced in the chloroplasts is consumed in the Calvin cycle, which produces
triose sugars.

[edit] ATP recycling

The total quantity of ATP in the human body is about 0.1 mole. The majority of
ATP is not usually synthesised de novo, but is generated from ADP by the
aforementioned processes. Thus, at any given time, the total amount of ATP +
ADP remains fairly constant.

The energy used by human cells requires the hydrolysis of 100 to 150 moles of
ATP daily, which is around 50 to 75 kg. A human will typically use up his or her
body weight of ATP over the course of the day.[32] This means that each ATP
molecule is recycled 1000 to 1500 times during a single day (100 / 0.1 = 1000).
ATP cannot be stored, hence its consumption closely follows its synthesis.
[edit] Regulation of biosynthesis

ATP production in an aerobic eukaryotic cell is tightly regulated by allosteric

mechanisms, by feedback effects, and by the substrate concentration dependence
of individual enzymes within the glycolysis and oxidative phosphorylation
pathways. Key control points occur in enzymatic reactions that are so energetically
favorable that they are effectively irreversible under physiological conditions.

In glycolysis, hexokinase is directly inhibited by its product, glucose-6-phosphate,

and pyruvate kinase is inhibited by ATP itself. The main control point for the
glycolytic pathway is phosphofructokinase (PFK), which is allosterically inhibited
by high concentrations of ATP and activated by high concentrations of AMP. The
inhibition of PFK by ATP is unusual, since ATP is also a substrate in the reaction
catalyzed by PFK; the biologically active form of the enzyme is a tetramer that
exists in two possible conformations, only one of which binds the second substrate
fructose-6-phosphate (F6P). The protein has two binding sites for ATP - the active
site is accessible in either protein conformation, but ATP binding to the inhibitor
site stabilizes the conformation that binds F6P poorly.[25] A number of other small
molecules can compensate for the ATP-induced shift in equilibrium conformation
and reactivate PFK, including cyclic AMP, ammonium ions, inorganic phosphate,
and fructose 1,6 and 2,6 biphosphate.[25]

The citric acid cycle is regulated mainly by the availability of key substrates,
particularly the ratio of NAD+ to NADH and the concentrations of calcium,
inorganic phosphate, ATP, ADP, and AMP. Citrate - the molecule that gives its
name to the cycle - is a feedback inhibitor of citrate synthase and also inhibits
PFK, providing a direct link between the regulation of the citric acid cycle and
glycolysis.[25]

In oxidative phosphorylation, the key control point is the reaction catalyzed by

cytochrome c oxidase, which is regulated by the availability of its substrate—the
reduced form of cytochrome c. The amount of reduced cytochrome c available is
directly related to the amounts of other substrates:

which directly implies this equation:

Thus, a high ratio of [NADH] to [NAD+] or a low ratio of [ADP] [Pi] to [ATP]
imply a high amount of reduced cytochrome c and a high level of cytochrome c
oxidase activity.[25] An additional level of regulation is introduced by the transport
rates of ATP and NADH between the mitochondrial matrix and the cytoplasm.[27]

[edit] Functions in cells

[edit] Metabolism, synthesis, and active transport

ATP is consumed in the cell by energy-requiring (endothermic) processes and can

be generated by energy-releasing (exothermic) processes. In this way ATP
transfers energy between spatially-separate metabolic reactions. ATP is the main
energy source for the majority of cellular functions. This includes the synthesis of
macromolecules, including DNA and RNA (see below), and proteins. ATP also
plays a critical role in the transport of macromolecules across cell membranes, e.g.
exocytosis and endocytosis.

[edit] Roles in cell structure and locomotion

ATP is critically involved in maintaining cell structure by facilitating assembly and

disassembly of elements of the cytoskeleton. In a related process, ATP is required
for the shortening of actin and myosin filament crossbridges required for muscle
contraction. This latter process is one of the main energy requirements of animals
and is essential for locomotion and respiration.

[edit] Cell signalling

[edit] Extracellular signalling

ATP is also a signalling molecule. ATP, ADP, or adenosine are recognised by

purinergic receptors. Purinoreceptors might be the most abundant receptors in
mammalian tissues (Abbracchio M.P. et al., 2008).

In humans, this signalling role is important in both the central and peripheral
nervous system. Activity-dependent release of ATP from synapses, axons and glia
activates purinergic membrane receptors known as P2.[33] The P2Y receptors are
metabotropic, i.e. G protein-coupled and modulate mainly intracellular calcium
and sometimes cyclic AMP levels. Though named between P2Y1 and P2Y15, only
nine members of the P2Y family have been cloned, and some are only related
through weak homology and several (P2Y5, P2Y7, P2Y9, P2Y10) do not function as
receptors that raise cytosolic calcium. The P2X ionotropic receptor subgroup
comprises seven members (P2X1–P2X7), which are ligand-gated Ca2+-permeable
ion channels that open when bound to an extracellular purine nucleotide. In
contrast to P2 receptors (agonist order ATP > ADP > AMP > ADO), purinergic
nucleotides like ATP are not strong agonists of P1 receptors, which are strongly
activated by adenosine and other nucleosides (ADO > AMP > ADP > ATP). P1
receptors have A1, A2a, A2b, and A3 subtypes ("A" as a remnant of old
nomenclature of adenosine receptor), all of which are G protein-coupled receptors,
A1 and A3 being coupled to Gi, and A2a and A2b being coupled to Gs.[34] All
adenosine receptors were shown to activate at least one subfamily of mitogen-
activated protein kinases. The actions of adenosine are often antagonistic or
synergistic to the actions of ATP. In the CNS, adenosine has multiple functions,
such as modulation of neural development, neuron and glial signalling and the
control of innate and adaptive immune systems (Abbracchio M.P. et al., 2008).

[edit] Intracellular signalling

ATP is critical in signal transduction processes. It is used by kinases as the source

of phosphate groups in their phosphate transfer reactions. Kinase activity on
substrates such as proteins or membrane lipids are a common form of signal
transduction. Phosphorylation of a protein by a kinase can activate this cascade
such as the mitogen-activated protein kinase cascade.[35]

ATP is also used by adenylate cyclase and is transformed to the second messenger
molecule cyclic AMP, which is involved in triggering calcium signals by the
release of calcium from intracellular stores.[36] This form of signal transduction is
particularly important in brain function, although it is involved in the regulation of
a multitude of other cellular processes.[37]

[edit] DNA and RNA synthesis

In all known organisms, the deoxyribonucleotides that make up DNA are

synthesized by the action of ribonucleotide reductase (RNR) enzymes on their
corresponding ribonucleotides.[38] These enzymes reduce the sugar residue from
ribose to deoxyribose by removing oxygen from the 2' hydroxyl group; the
substrates are ribonucleoside diphosphates and the products deoxyribonucleoside
diphosphates (the latter are denoted dADP, dCDP, dGDP, and dUDP respectively.)
All ribonucleotide reductase enzymes use a common sulfhydryl radical mechanism
reliant on reactive cysteine residues that oxidize to form disulfide bonds in the
course of the reaction.[38] RNR enzymes are recycled by reaction with thioredoxin
or glutaredoxin.[25]
The regulation of RNR and related enzymes maintains a balance of dNTPs relative
to each other and relative to NTPs in the cell. Very low dNTP concentration
inhibits DNA synthesis and DNA repair and is lethal to the cell, while an abnormal
ratio of dNTPs is mutagenic due to the increased likelihood of the DNA
polymerase incorporating the wrong dNTP during DNA synthesis.[25] Regulation of
or differential specificity of RNR has been proposed as a mechanism for alterations
in the relative sizes of intracellular dNTP pools under cellular stress such as
hypoxia.[39]

In the synthesis of the nucleic acid RNA, ATP is one of the four nucleotides
incorporated directly into RNA molecules by RNA polymerases. The energy
driving this polymerization comes from cleaving off a pyrophosphate (two
phosphate groups).[40] The process is similar in DNA biosynthesis, except that ATP
is reduced to the deoxyribonucleotide dATP, before incorporation into DNA.

[edit] Binding to proteins

An example of the Rossmann fold, a structural domain of a decarboxylase enzyme

from the bacterium Staphylococcus epidermidis (PDB ID 1G5Q) with a bound
flavin mononucleotide cofactor.

Some proteins that bind ATP do so in a characteristic protein fold known as the
Rossmann fold, which is a general nucleotide-binding structural domain that can
also bind the coenzyme NAD.[41] The most common ATP-binding proteins, known
as kinases, share a small number of common folds; the protein kinases, the largest
kinase superfamily, all share common structural features specialized for ATP
binding and phosphate transfer.[42]

ATP in complexes with proteins, in general, requires the presence of a divalent

cation, almost always magnesium, which binds to the ATP phosphate groups. The
presence of magnesium greatly decreases the dissociation constant of ATP from its
protein binding partner without affecting the ability of the enzyme to catalyze its
reaction once the ATP has bound.[43] The presence of magnesium ions can serve as
a mechanism for kinase regulation.[44]

[edit] ATP analogues

Biochemistry laboratories often use in vitro studies to explore ATP-dependent
molecular processes. Enzyme inhibitors of ATP-dependent enzymes such as
kinases are needed to examine the binding sites and transition states involved in
ATP-dependent reactions. ATP analogs are also used in X-ray crystallography to
determine a protein structure in complex with ATP, often together with other
substrates. Most useful ATP analogs cannot be hydrolyzed as ATP would be;
instead they trap the enzyme in a structure closely related to the ATP-bound state.
Adenosine 5'-(gamma-thiotriphosphate) is an extremely common ATP analog in
which one of the gamma-phosphate oxygens is replaced by a sulfur atom; this
molecule is hydrolyzed at a dramatically slower rate than ATP itself and functions
as an inhibitor of ATP-dependent processes. In crystallographic studies, hydrolysis
transition states are modeled by the bound vanadate ion. However, caution is
warranted in interpreting the results of experiments using ATP analogs, since some
enzymes can hydrolyze them at appreciable rates at high concentration.[

Adenosine diphosphate, abbreviated ADP, is a nucleotide. It is an ester of

pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group,
the pentose sugar ribose, and the nucleobase adenine.

ADP is the product of ATP dephosphorylation by ATPases. ADP is converted back to ATP by
ATP synthases. ATP is an important energy transfer molecule in cells.

ADP is stored in dense bodies inside blood platelets and is released upon platelet activation.
ADP interacts with a family of ADP receptors found on platelets (P2Y1, P2Y12 and P2X1),
leading to further platelet activation.[1] ADP in the blood is converted to adenosine by the action
of ecto-ADPases, inhibiting further platelet activation via adenosine receptors.

ADP is the end-product that results when ATP loses one of its phosphate groups located at the
end of the molecule.[2] The conversion of these two molecules plays a critical role in supplying
energy for many processes of life.[2] The deletion of one of ATP’s phosphorus bonds generates
approximately 7.3 kilocalories per Mole of ATP.[3] ADP can be converted, or powered back to
ATP through the process of releasing the chemical energy available in food; in humans this is
constantly performed via aerobic respiration in the mitochondria.[2] Plants use photosynthetic
pathways to convert and store the energy from sunlight, via conversion of ADP to ATP.[3]
Animals use the energy released in the breakdown of glucose and other molecules to convert
ADP to ATP, which can then be used to fuel necessary growth and cell maintenance.[2]

Single nucleotides (ADP) have the ability to catalyze organic reactions. This has relevance for
prebiotic studies of the RNA world and DNA world hypothesis for the origin of life on Earth.[4]

Phosphocreatine, also known as creatine phosphate or PCr (Pcr), is a

phosphorylated creatine molecule that serves as a rapidly mobilizable reserve of high-energy
phosphates in skeletal muscle and brain.

Phosphocreatine is formed from parts of three amino acids: arginine (Arg), glycine (Gly), and
methionine (Met). It can be synthesized by formation of guanidinoacetate from Arg and Gly (in
kidney) followed by methylation (S-adenosyl methionine is required) to creatine (in liver), and
phosphorylation by creatine kinase (ATP is required) to phosphocreatine (in muscle);
catabolism: dehydration to form the cyclic Shiff base creatinine. Phosphocreatine is synthesized
in the liver and transported to the muscle cells, via the bloodstream, for storage.

The creatine phosphate shuttle facilitates transport of high energy phosphate from mitochondria.

[edit] Function
Phosphocreatine can anaerobically donate a phosphate group to ADP to form ATP during the
first 2 to 7 seconds following an intense muscular or neuronal effort. On the converse, excess
ATP can be used during a period of low effort to convert creatine to phosphocreatine. The
reversible phosphorylation of creatine (i.e., both the forward and backward reaction) is catalyzed
by several creatine kinases. The presence of creatine kinase (CK-MB, MB for muscle/brain) in
plasma is indicative of tissue damage and is used in the diagnosis of myocardial infarction.[1] The
cell's ability to generate phosphocreatine from excess ATP during rest, as well as its use of
phosphocreatine for quick regeneration of ATP during - in this case, ATP. Phosphocreatine plays
a particularly important role in tissues that have high, fluctuating energy demands such as muscle
and brain.
The phosphagens are energy storage compounds, also known as high-energy
phosphate compounds, are chiefly found in muscular tissue in animals. They allow a high-energy
phosphate pool to be maintained in a concentration range, which, if it all were ATP, would create
problems due to the ATP consuming reactions in these tissues. As muscle tissues can have
sudden demands for lots of energy; these compounds can maintain a reserve of high-energy
phosphates that can be used as needed, to provide the energy that could not be immediately
supplied by glycolysis or oxidative phosphorylation.

The actual biomolecule used as a phosphagen is dependent on the organism. The majority of
animals use arginine/phosphoarginine as phosphagens; however, the phylum Chordata (i.e.,
animals with spinal cords) use creatine. Creatine phosphate, or phosphocreatine, is made from
ATP by the enzyme creatine kinase in a reversible reaction:

 Creatine + ATP creatine phosphate + ADP (this reaction is Mg++-dependent)

However, annelids (segmented worms) use a set of unique phosphagens; for example,
earthworms use the compound lombricine.

Glycogen is a molecule that serves as the secondary long-term energy storage in

animal and fungal cells, with the primary energy stores being held in adipose tissue. Glycogen is
made primarily by the liver and the muscles, but can also be made by glycogenesis within the
brain and stomach.[2]

Glycogen is the analogue of starch, a less branched glucose polymer in plants, and is sometimes
referred to as animal starch, having a similar structure to amylopectin. Glycogen is found in the
form of granules in the cytosol/cytoplasm in many cell types, and plays an important role in the
glucose cycle. Glycogen forms an energy reserve that can be quickly mobilized to meet a sudden
need for glucose, but one that is less compact than the energy reserves of triglycerides (lipids).

In the liver hepatocytes, glycogen can compose up to eight percent of the fresh weight (100–
120 g in an adult) soon after a meal.[3] Only the glycogen stored in the liver can be made
accessible to other organs. In the muscles, glycogen is found in a low concentration (one to two
percent of the muscle mass). However, the amount of glycogen stored in the body—especially
within the muscles, liver, and red blood cells[4][5][6]—mostly depends on physical training, basal
metabolic rate, and eating habits such as intermittent fasting. Small amounts of glycogen are
found in the kidneys, and even smaller amounts in certain glial cells in the brain and white blood
cells. The uterus also stores glycogen during pregnancy to nourish the embryo.[7]
Main article: Glycogenolysis

Glycogen is cleaved from the nonreducing ends of the chain by the enzyme glycogen
phosphorylase to produce monomers of glucose-1-phosphate, which is then converted to glucose
6-phosphate by phosphoglucomutase. A special debranching enzyme is needed to remove the
alpha(1-6) branches in branched glycogen and reshape the chain into linear polymer. The G6P
monomers produced have three possible fates:

 G6P can continue on the glycolysis pathway and be used as fuel.

 G6P can enter the pentose phosphate pathway via the enzyme Glucose-6-phosphate
dehydrogenase to produce NADPH and 5-carbon sugars.
 In the liver and kidney, G6P can be dephosphorylated back to Glucose by the enzyme
Glucose 6-phosphatase. This is the final step in the gluconeogenesis pathway.

Glycolysis (from glycose, an older term [1]

for glucose + -lysis degradation) is the
metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+. The free
energy released in this process is used to form the high-energy compounds ATP (adenosine
triphosphate) and NADH (reduced nicotinamide adenine dinucleotide).

Glycolysis is a definite sequence of ten reactions involving ten intermediate compounds (one of
the steps involves two intermediates). The intermediates provide entry points to glycolysis. For
example, most monosaccharides, such as fructose, glucose, and galactose, can be converted to
one of these intermediates. The intermediates may also be directly useful. For example, the
intermediate dihydroxyacetone phosphate (DHAP) is a source of the glycerol that combines with
fatty acids to form fat.

It occurs, with variations, in nearly all organisms, both aerobic and anaerobic. The wide
occurrence of glycolysis indicates that it is one of the most ancient known metabolic pathways.[2]
The most common type of glycolysis is the Embden-Meyerhof-Parnas pathway (EMP pathway),
which was first discovered by Gustav Embden, Otto Meyerhof and Jakub Karol Parnas.
Glycolysis also refers to other pathways, such as the Entner–Doudoroff pathway and various
heterofermentative and homofermentative pathways. However, the discussion here will be
limited to the Embden-Meyerhof pathway.

Glycogenolysis

Glycogenolysis (also known as "Glycogenlysis") is the conversion of glycogen polymers to

glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage
with inorganic phosphate to produce glucose-1-phosphate.[1] This derivative of glucose is then
converted to glucose-6-phosphate, an intermediate in glycolysis.

The hormones glucagon and epinephrine stimulate glycogenolysis.

Function
Glycogenolysis takes place in the muscle and liver tissues, where glycogen is stored, as a
hormonal response to epinephrine (e.g., adrenergic stimulation) and/or glucagon, a pancreatic
peptide triggered by low blood glucose concentrations, and produced in the alpha cells of the
islets of Langerhans.

 Liver (hepatic) cells can consume the glucose-6-phosphate in glycolysis or remove the
phosphate group using the enzyme glucose-6-phosphatase and release the free glucose
into the bloodstream for uptake by other cells.

 Muscle cells in humans do not possess glucose-6-phosphatase and, hence, will not release
glucose, but instead use the glucose-6-phosphate in glycolysis.

Anaerobic glycolysis is the transformation of glucose to pyruvate when

limited amounts of oxygen (O2) are available. Anaerobic glycolysis is only an effective
means of energy production during short, intense exercise, providing energy for a period
ranging from 10 seconds to 2 minutes. The anaerobic glycolysis (lactic acid) system is
dominant from about 10–30 seconds during a maximal effort. It replenishes very quickly
over this period and produces 2 ATP molecules per glucose molecule, or about 5% of
 glucose's energy potential (38 ATP molecules). The speed at which ATP is produced is
about 100 times that of oxidative phosphorylation. The pH in the cytoplasm quickly
drops when hydrogen ions accumulate in the muscle, eventually inhibiting enzymes
involved in glycolosis.

 The burning sensation in muscles during hard exercise can be attributed to the production
of hydrogen ions during a shift to anaerobic glycolysis as oxygen is converted to carbon
dioxide by aerobic glycolysis faster than the body can replenish it. These hydrogen ions
form a part of lactic acid along with lactate. The body falls back on this less efficient but
faster method of producing ATP under low oxygen conditions. This is thought to have
been the primary means of energy production in earlier organisms before oxygen was at
high concentration in the atmosphere and thus would represent a more ancient form of
energy production in cells.
 The liver later gets rid of this excess lactate by transforming it back into an important
glycolytic intermediate called pyruvate. Aerobic glycolysis is a method employed by
muscle cells for the production of lower-intensity energy over a longer period of time.
 The process of converting the excess lactate back into pyruvate is known as the Cori
cycle, and occurs in the liver.
 Many anaerobic microorganisms carry out Anaerobic Glycolysis through Fermentation.

Carbohydrate metabolism denotes the various biochemical processes responsible

for the formation, breakdown and interconversion of carbohydrates in living organisms.

The most important carbohydrate is glucose, a simple sugar (monosaccharide) that is

metabolized by nearly all known organisms. Glucose and other carbohydrates are part of a wide
variety of metabolic pathways across species: plants synthesize carbohydrates from atmospheric
gases by photosynthesis storing the absorbed energy internally, often in the form of starch or
lipids. Plant components are eaten by animals and fungi, and used as fuel for cellular respiration.
Oxidation of one gram of carbohydrate yields approximately 4 kcal of energy and from lipids
about 9 kcal. Energy obtained from metabolism (e.g. oxidation of glucose) is usually stored
temporarily within cells in the form of ATP. Organisms capable of aerobic respiration
metabolize glucose and oxygen to release energy with carbon dioxide and water as byproducts.

Carbohydrates are a superior short-term fuel for organisms because they are simpler to
metabolize than fats or those amino acid portions of proteins that are used for fuel. In animals,
the most important carbohydrate is glucose; so much so, that the level of glucose is used as the
main control for the central metabolic hormone, insulin. Starch, and cellulose in a few organisms
(e.g., termites, ruminants, and some bacteria), both being glucose polymers, are disassembled
during digestion and absorbed as glucose. Some simple carbohydrates have their own enzymatic
oxidation pathways, as do only a few of the more complex carbohydrates. The disaccharide
lactose, for instance, requires the enzyme lactase to be broken into its monosaccharides
components; many animals lack this enzyme in adulthood.

Carbohydrates are typically stored as long polymers of glucose molecules with glycosidic bonds
for structural support (e.g. chitin, cellulose) or for energy storage (e.g. glycogen, starch).
However, the strong affinity of most carbohydrates for water makes storage of large quantities of
carbohydrates inefficient due to the large molecular weight of the solvated water-carbohydrate
complex. In most organisms, excess carbohydrates are regularly catabolised to form acetyl-CoA,
which is a feed stock for the fatty acid synthesis pathway; fatty acids, triglycerides, and other
lipids are commonly used for long-term energy storage. The hydrophobic character of lipids
makes them a much more compact form of energy storage than hydrophilic carbohydrates.
However, animals, including humans, lack the necessary enzymatic machinery and so do not
synthesize glucose from lipids.[1]

All carbohydrates share a general formula of approximately CnH2nOn; glucose is C6H12O6.

Monosaccharides may be chemically bonded together to form disaccharides such as sucrose and
longer polysaccharides such as starch and cellulose.

 Carbon fixation, or photosynthesis, in which CO2 is reduced to carbohydrate.

 Glycolysis - the oxidation metabolism of glucose molecules to obtain ATP and pyruvate
o Pyruvate from glycolysis enters the Krebs cycle, also known as the citric acid
cycle, in aerobic organisms after moving through pyruvate dehydrogenase
complex.
 The pentose phosphate pathway, which acts in the conversion of hexoses into pentoses
and in NADPH regeneration.
 Glycogenesis - the conversion of excess glucose into glycogen as a cellular storage
mechanism; this prevents excessive osmotic pressure buildup inside the cell
 Glycogenolysis - the breakdown of glycogen into glucose, which provides a glucose
supply for glucose-dependent tissues.
 Gluconeogenesis - de novo synthesis of glucose molecules from simple organic
compounds. an example in humans is the conversion of a few amino acids in cellular
protein to glucose.

Metabolic use of glucose is highly important as an energy source for muscle cells and in the
brain, and red blood cells.
Unit III

Fats consist of a wide group of compounds that are generally soluble in organic solvents
and generally insoluble in water. Chemically, fats are generally triesters of glycerol and fatty
acids. Fats may be either solid or liquid at room temperature, depending on their structure and
composition. Although the words "oils", "fats", and "lipids" are all used to refer to fats, "oils" is
usually used to refer to fats that are liquids at normal room temperature, while "fats" is usually
used to refer to fats that are solids at normal room temperature. "Lipids" is used to refer to both
liquid and solid fats, along with other related substances. The word "oil" is also used for any
substance that does not mix with water and has a greasy feel, such as petroleum (or crude oil),
heating oil, and essential oils, regardless of its chemical structure.[1]

Fats form a category of lipid, distinguished from other lipids by their chemical structure and
physical properties. This category of molecules is important for many forms of life, serving both
structural and metabolic functions. They are an important part of the diet of most heterotrophs
(including humans). Fats or lipids are broken down in the body by enzymes called lipases
produced in the pancreas.

Examples of edible animal fats are lard, fish oil, and butter or ghee. They are obtained from fats
in the milk and meat, as well as from under the skin, of an animal. Examples of edible plant fats
include peanut, soya bean, sunflower, sesame, coconut, olive, and vegetable oils. Margarine and
vegetable shortening, which can be derived from the above oils, are used mainly for baking.
These examples of fats can be categorized into saturated fats and unsaturated fats.

Chemical structure
There are many different kinds of fats, but each is a variation on the same chemical structure. All
fats consist of fatty acids (chains of carbon and hydrogen atoms, with a carboxylic acid group at
one end) bonded to a backbone structure, often glycerol (a "backbone" of carbon, hydrogen, and
oxygen). Chemically, this is a triester of glycerol, an ester being the molecule formed from the
reaction of the carboxylic acid and an organic alcohol. As a simple visual illustration, if the kinks
and angles of these chains were straightened out, the molecule would have the shape of a capital
letter E. The fatty acids would each be a horizontal line; the glycerol "backbone" would be the
vertical line that joins the horizontal lines. Fats therefore have "ester" bonds.

The properties of any specific fat molecule depend on the particular fatty acids that constitute it.
Different fatty acids are composed of different numbers of carbon and hydrogen atoms. The
carbon atoms, each bonded to two neighboring carbon atoms, form a zigzagging chain; the more
carbon atoms there are in any fatty acid, the longer its chain will be. Fatty acids with long chains
are more susceptible to intermolecular forces of attraction (in this case, van der Waals forces),
raising its melting point. Long chains also yield more energy per molecule when metabolized.
Triglyceride

A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three
fatty acids.[1] It is the main constituent of vegetable oil and animal fats.

Triglycerides are formed by combining glycerol with three molecules of fatty acid. The glycerol
molecule has three hydroxyl (HO-) groups. Each fatty acid has a carboxyl group (COOH). In
triglycerides, the hydroxyl groups of the glycerol join the carboxyl groups of the fatty acid to
form ester bonds[citation needed]:

HOCH2CH(OH)CH2OH + RCO2H + R'CO2H + R''CO2H → RCO2CH2CH(O2CR')CR'' +

3H2O

The three fatty acids (RCO2H, R'CO2H, R''CO2H in the above equation) are usually different, but
many kinds of triglycerides are known. The chain lengths of the fatty acids in naturally occurring
triglycerides vary, but most contain 16, 18, or 20 carbon atoms. Natural fatty acids found in
plants and animals are typically composed of only even numbers of carbon atoms, reflecting the
pathway for their biosynthesis from the two-carbon building-block acetyl CoA. Bacteria,
however, possess the ability to synthesise odd- and branched-chain fatty acids. As a result,
ruminant animal fat contains odd-numbered fatty acids, such as 15, due to the action of bacteria
in the rumen. Many fatty acids are unsaturated, some are polyunsaturated, e.g., those derived
from linoleic acid.[citation needed]

Most natural fats contain a complex mixture of individual triglycerides. Because of this, they
melt over a broad range of temperatures. Cocoa butter is unusual in that it is composed of only a
few triglycerides, derived from palmitic, oleic, and stearic acids.

Metabolism
The enzyme pancreatic lipase acts at the ester bond, hydrolysing the bond and "releasing" the
fatty acid. In triglyceride form, lipids cannot be absorbed by the duodenum. Fatty acids,
monoglycerides (one glycerol, one fatty acid), and some diglycerides are absorbed by the
duodenum, once the triglycerides have been broken down.

See also: fatty acid metabolism

Triglycerides, as major components of very-low-density lipoprotein (VLDL) and chylomicrons,

play an important role in metabolism as energy sources and transporters of dietary fat. They
contain more than twice as much energy (9 kcal/g or 38 kJ/g ) as carbohydrates and proteins. In
the intestine, triglycerides are split into monoacylglycerol and free fatty acids in a process called
lipolysis, with the secretion of lipases and bile, which are subsequently moved to absorptive
enterocytes, cells lining the intestines. The triglycerides are rebuilt in the enterocytes from their
fragments and packaged together with cholesterol and proteins to form chylomicrons. These are
excreted from the cells and collected by the lymph system and transported to the large vessels
near the heart before being mixed into the blood. Various tissues can capture the chylomicrons,
releasing the triglycerides to be used as a source of energy. Fat and liver cells can synthesize and
store triglycerides. When the body requires fatty acids as an energy source, the hormone
glucagon signals the breakdown of the triglycerides by hormone-sensitive lipase to release free
fatty acids. As the brain cannot utilize fatty acids as an energy source (unless converted to a
ketone), the glycerol component of triglycerides can be converted into glucose, via glycolysis by
conversion into Dihydroxyacetone phosphate and then into Glyceraldehyde 3-phosphate, for
brain fuel when it is broken down. Fat cells may also be broken down for that reason, if the
brain's needs ever outweigh the body's.

Triglycerides cannot pass through cell membranes freely. Special enzymes on the walls of blood
vessels called lipoprotein lipases must break down triglycerides into free fatty acids and glycerol.
Fatty acids can then be taken up by cells via the fatty acid transporter (FAT).

Cholesterol is a waxy steroid of fat that is produced in the liver or intestines. It is used
to produce hormones and cell membranes and is transported in the blood plasma of all
mammals.[2] It is an essential structural component of mammalian cell membranes and is
required to establish proper membrane permeability and fluidity. In addition, cholesterol is an
important component for the manufacture of bile acids, steroid hormones, and Vitamin D.
Cholesterol is the principal sterol synthesized by animals; however, small quantities can be
synthesized in other eukaryotes such as plants and fungi. It is almost completely absent among
prokaryotes including bacteria.[3] Although cholesterol is important and necessary for mammals,
high levels of cholesterol in the blood can damage arteries and are potentially linked to diseases
such as those associated with the cardiovascular system (heart disease).[4]

The name cholesterol originates from the Greek chole- (bile) and stereos (solid), and the
chemical suffix -ol for an alcohol. François Poulletier de la Salle first identified cholesterol in
solid form in gallstones, in 1769. However, it was only in 1815 that chemist Eugène Chevreul
named the compound "cholesterine".[5]
Function

Cholesterol is required to build and maintain membranes; it modulates membrane fluidity over
the range of physiological temperatures. The hydroxyl group on cholesterol interacts with the
polar head groups of the membrane phospholipids and sphingolipids, while the bulky steroid and
the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty acid chain of
the other lipids. In this structural role, cholesterol reduces the permeability of the plasma
membrane to protons (positive hydrogen ions) and sodium ions.[7]

Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and
nerve conduction. Cholesterol is essential for the structure and function of invaginated caveolae
and clathrin-coated pits, including caveola-dependent and clathrin-dependent endocytosis. The
role of cholesterol in such endocytosis can be investigated by using methyl beta cyclodextrin
(MβCD) to remove cholesterol from the plasma membrane. Recently, cholesterol has also been
implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma
membrane. In many neurons, a myelin sheath, rich in cholesterol, since it is derived from
compacted layers of Schwann cell membrane, provides insulation for more efficient conduction
of impulses.[8]

Within cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver,
cholesterol is converted to bile, which is then stored in the gallbladder. Bile contains bile salts,
which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as
well as the fat-soluble vitamins, Vitamin A, Vitamin D, Vitamin E, and Vitamin K. Cholesterol
is an important precursor molecule for the synthesis of Vitamin D and the steroid hormones,
including the adrenal gland hormones cortisol and aldosterone as well as the sex hormones
progesterone, estrogens, and testosterone, and their derivatives.

Some research indicates that cholesterol may act as an antioxidant.[9]

High-density lipoprotein (HDL) is one of the five major groups of

lipoproteins which, in order of sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL and
HDL, which enable lipids like cholesterol and triglycerides to be transported within the water-
based bloodstream. In healthy individuals, about thirty percent of blood cholesterol is carried by
HDL.[1]

Blood tests typically report HDL-C level, i.e. the amount of cholesterol contained in HDL
particles. It is often contrasted with low density or LDL cholesterol or LDL-C. HDL particles are
able to remove cholesterol from within artery atheroma[citation needed] and transport it back to the
liver for excretion or re-utilization, which is the main reason why the cholesterol carried within
HDL particles (HDL-C) is sometimes called "good cholesterol" (despite the fact that it is exactly
the same as the cholesterol in LDL particles). Those with higher levels of HDL-C seem to have
fewer problems with cardiovascular diseases, while those with low HDL-C cholesterol levels
(less than 40 mg/dL or about 1 mmol/L) have increased rates for heart disease.[2] While higher
HDL levels are correlated with cardiovascular health, no incremental increase in HDL has been
proven to improve health. In other words, while high HDL levels might correlate with better
cardiovascular health, specifically increasing one's HDL might not increase cardiovascular
health.[3] Additionally, those few individuals producing an abnormal, apparently more efficient,
HDL ApoA1 protein variant called ApoA-1 Milano, have low measured HDL-C levels yet very
low rates of

Structure and function

HDL is the smallest of the lipoprotein particles. They are the densest because they contain the
highest proportion of protein to cholesterol. Their most abundant apolipoproteins are apo A-I and
apo A-II.[4] The liver synthesizes these lipoproteins as complexes of apolipoproteins and
phospholipid, which resemble cholesterol-free flattened spherical lipoprotein particles. They are
capable of picking up cholesterol, carried internally, from cells by interaction with the ATP-
binding cassette transporter A1 (ABCA1). A plasma enzyme called lecithin-cholesterol
acyltransferase (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic
form of cholesterol), which is then sequestered into the core of the lipoprotein particle,
eventually making the newly synthesized HDL spherical. They increase in size as they circulate
through the bloodstream and incorporate more cholesterol and phospholipid molecules from cells
and other lipoproteins, for example by the interaction with the ABCG1 transporter and the
phospholipid transport protein (PLTP).

HDL transports cholesterol mostly to the liver or steroidogenic organs such as adrenals, ovary,
and testes by direct and indirect pathways. HDL is removed by HDL receptors such as scavenger
receptor BI (SR-BI), which mediate the selective uptake of cholesterol from HDL. In humans,
probably the most relevant pathway is the indirect one, which is mediated by cholesteryl ester
transfer protein (CETP). This protein exchanges triglycerides of VLDL against cholesteryl esters
of HDL. As the result, VLDLs are processed to LDL, which are removed from the circulation by
the LDL receptor pathway. The triglycerides are not stable in HDL, but degraded by hepatic
lipase so that finally small HDL particles are left, which restart the uptake of cholesterol from
cells.

The cholesterol delivered to the liver is excreted into the bile and, hence, intestine either directly
or indirectly after conversion into bile acids. Delivery of HDL cholesterol to adrenals, ovaries,
and testes is important for the synthesis of steroid hormones.

Several steps in the metabolism of HDL can contribute to the transport of cholesterol from lipid-
laden macrophages of atherosclerotic arteries, termed foam cells, to the liver for secretion into
the bile. This pathway has been termed reverse cholesterol transport and is considered as the
classical protective function of HDL toward atherosclerosis.\
However, HDL carries many lipid and protein species, several of which have very low
concentrations but are biologically very active. For example, HDL and their protein and lipid
constituents help to inhibit oxidation, inflammation, activation of the endothelium, coagulation,
and platelet aggregation. All these properties may contribute to the ability of HDL to protect
from atherosclerosis, and it is not yet known what are the most important.

In the stress response, serum amyloid A, which is one of the acute-phase proteins and an
apolipoprotein, is under the stimulation of cytokines (IL-1, IL-6), and cortisol produced in the
adrenal cortex and carried to the damaged tissue incorporated into HDL particles. At the
inflammation site, it attracts and activates leukocytes. In chronic inflammations, its deposition in
the tissues manifests itself as amyloidosis.

It has been postulated that the concentration of large HDL particles more accurately reflects
protective action, as opposed to the concentration of total HDL particles.[5] This ratio of large
HDL to total HDL particles varies widely and is measured only by more sophisticated
lipoprotein assays using either electrophoresis (the original method developed in the 1970s) or
newer NMR spectroscopy methods (See also: NMR and spectroscopy), developed in the 1990s.

Low-density lipoprotein (LDL) is one of the five major groups of

lipoproteins, which in order of size, largest to smallest, are chylomicrons, VLDL, IDL, LDL and
HDL, that enable transport of lipids like cholesterol and triglycerides within the water-based
bloodstream. Blood tests typically report LDL-C, the amount of cholesterol contained in LDL. In
clinical context, mathematically calculated estimates of LDL-C are commonly used to estimate
how much low density lipoproteins are driving progression of atherosclerosis. Direct LDL
measurements are also available and better reveal individual issues but are less often promoted or
done due to slightly higher costs and being available from only a couple of laboratories in the
United States. In 28 March 2008, as part of a joint consensus statement by the ADA and ACC,
direct LDL particle measurement by NMR was recognized as superior for assessing individual
risk of cardiovascular events.[1] Because previous studies showed that higher levels of LDL
particles promote health problems and cardiovascular disease, they are often informally called
the bad cholesterol particles, (as opposed to HDL particles, which are frequently referred to as
good cholesterol or healthy cholesterol particles).[2] A recent study has found that LDL is
essential in building muscle during resistance training.[3]
Structure

Each native LDL particle contains a single apolipoprotein B-100 molecule (Apo B-100, a protein
with 4536 amino acid residues), which circulates the fatty acids, keeping them soluble in the
aqueous environment. In addition, LDL has a highly-hydrophobic core consisting of
polyunsaturated fatty acid known as linoleate and about 1500 esterified cholesterol molecules.
This core is surrounded by a shell of phospholipids and unesterified cholesterol, as well as a
single copy of B-100 large protein (514 kD). LDL particles are approximately 22 nm
(0.00000087 in.) in diameter and have a mass of about 3 million daltons, but since LDL particles
contain a changing number of fatty acids, they actually have a distribution of mass and size.[4]
Determining structure of LDL has been a tough task because of its heterogeneous structure. First
structure of LDL at human body temperature in native condition has been recently found using
cryo-electron microscopy and it has resolution of 16 Angstrom.[5]

[edit] LDL subtype patterns

LDL particles vary in size and density, and studies have shown that a pattern that has more small
dense LDL particles, called Pattern B, equates to a higher risk factor for coronary heart disease
(CHD) than does a pattern with more of the larger and less dense LDL particles (Pattern A). This
is because the smaller particles are more easily able to penetrate the endothelium. Pattern I, for
intermediate, indicates that most LDL particles are very close in size to the normal gaps in the
endothelium (26 nm).[citation needed]

Some in the medical community have suggested the correspondence between Pattern B and CHD
is stronger than the correspondence between the LDL number measured in the standard lipid
profile test. Tests to measure these LDL subtype patterns have been more expensive and not
widely available, so the common lipid profile test is used more commonly.[citation needed]

There has also been noted a correspondence between higher triglyceride levels and higher levels
of smaller, denser LDL particles and alternately lower triglyceride levels and higher levels of the
larger, less dense LDL.[6][7]

With continued research, decreasing cost, greater availability and wider acceptance of other
lipoprotein subclass analysis assay methods, including NMR spectroscopy,[8] research studies
have continued to show a stronger correlation between human clinically obvious cardiovascular
event and quantitatively-measured particle concentrations.[citation needed]
Very low density lipoprotein, also known as VLDL cholesterol, is a form of
cholesterol that helps to distribute trigylicerides through the bloodstream. A portion of this type
of cholesterol also converts into LDL or low density protein cholesterol, which can eventually
clog blood vessels and lead to a number of health issues. Because of this conversion, physicians
tend to monitor VLDL cholesterol levels along with LDL and HDL levels.

Unlike the processes for measuring the levels of HDL and LDL cholesterol present in the system,
it is necessary to prepare an estimate of VLDL levels in the body. This is accomplished by
identifying a percentage of the trigylercide level present. For the most part, a reading of
anywhere between five and forty milligrams per deciliter is considered within normal range,
although physicians tend to encourage patients to make lifestyle changes when the reading is at
the upper end of this range.

When it is necessary to lower VLDL cholesterol levels, this is best accomplished by consuming
foods that do not promote the collection of high amounts of LDL and triglycerides in the system.
This often means minimizing or eliminating fatty meats as well as cutting back of processed
sugars. Limiting alcohol consumption is also often recommended.

In addition to limiting or eliminating certain foods from the diet, doctors often encourage
patients with higher levels of VLDL cholesterol to consume more green vegetables, fresh fruits
and whole grains. This can help to increase the amount of fiber in the diet, which will also help
to lower cholesterol levels in the bloodstream.

Along with dietary changes, physicians often recommend that patients make it a point to exercise
on a regular basis. Physical activity sustained for at least a period of thirty minutes can help
promote healthier levels of high density lipoproteins in the body while also lowering LDL and
VLDL levels.

When high VLDL cholesterol levels are identified, doctors may also address the issue of the
patient’s weight. If the patient is carrying around a few extra pounds, the physician will often
encourage the patient to lose enough weight to get back into what is considered a healthy range.
Exercise and diet will both help with this effort; in addition, losing the weight means less stored
fat in the system and less bad cholesterol in the body overall.

Taking steps to keep VLDL cholesterol levels within an acceptable range is just as important as
maintaining good or HDL levels and lowering LDL levels. Seeking to balance all these factors
will help to minimize the chances for strokes, heart attacks, and other conditions involving the
coronary system.

Role of fat on energy metabolism

Fatty acids are an important source of energy and adenosine triphosphate (ATP) for many cellular
organisms. Excess fatty acids, glucose, and other nutrients can be stored efficiently as fat. Triglycerides
yield more than twice as much energy for the same mass as do carbohydrates or proteins. All cell
membranes are built up of phospholipids, each of which contains two fatty acids. Fatty acids are also
used for protein modification. The metabolism of fatty acids, therefore, consists of catabolic processes
that generate energy and primary metabolites from fatty acids, and anabolic processes that create
biologically important molecules from fatty acids and other dietary carbon sources.

Fatty acids as an energy source

Fatty acids, stored as triglycerides in an organism, are an important source of energy because
they are both reduced and anhydrous. The energy yield from a gram of fatty acids is
approximately 9 Kcal (37 kJ), compared to 4 Kcal/g (17 kJ/g) for carbohydrates. Since the
hydrocarbon portion of fatty acids is hydrophobic, these molecules can be stored in a relatively
anhydrous (water-free) environment. Carbohydrates, on the other hand, are more highly
hydrated. For example, 1 g of glycogen can bind approximately 2 g of water, which translates to
1.33 Kcal/g (4 Kcal/3 g). This means that fatty acids can hold more than six times the amount of
energy per unit of storage mass. Put another way, if the human body relied on carbohydrates to
store energy, then a person would need to carry 67.5 lb (31 kg) of hydrated glycogen to have the
energy equivalent to 10 lb (5 kg) of fat. Hibernating animals provide a good example for
utilizing fat reserves as fuel. For example, bears hibernate for about 7 months, and, during this
entire period, the energy is derived from degradation of fat stores.

Unit V

Acid-base balance
Definition
Acid-base balance can be defined as homeostasis of the body fluids at a normal arterial blood pH ranging
between 7.37 and 7.43.
Description
An acid is a substance that acts as a proton donor. In contrast, a base, also known as an alkali, is frequently
defined as a substance that combines with a proton to form a chemical bond. Acid solutions have a sour taste
and produce a burning sensation with skin contact. A base is any chemical compound that produces hydroxide
ions when dissolved in water. Base solutions have a bitter taste and a slippery feel. Despite variations
in metabolism, diet, and environmental factors, the body's acid-base balance, fluid volume, and electrolyte
concentration are maintained within a narrow range.
Function
Many naturally occurring acids are necessary for life. For example, hydrochloric acid is secreted by
the stomach to assist with digestion. The chemical composition of food in the diet can have an effect on the
body's acid-base production. Components that affect acid-base balance include protein, chloride, phosphorus,
sodium, potassium, calcium, and magnesium. In addition, the rate at which nutrients are absorbed in the
intestine will alter acid-base balance.
Cells and body fluids contain acid-base buffers, which help prevent rapid changes in body fluid pH over short
periods of time, until the kidneys pulmonary systems can make appropriate adjustments. The kidneys and
pulmonary system then work to maintain acid-base balance through excretion in the urine or respiration. The
partial pressure of carbon dioxide gas (PCO2) in the pulmonary system can be measured with a blood sample
and correlates with blood carbon dioxide (CO2) levels. PCO2 can then be used as an indicator of the
concentration of acid in the body. The concentration of base in the body can be determined by measuring
plasma bicarbonate (HCO3-) concentration. When the acid-base balance is disturbed, the respiratory
system can alter PCO2quickly, thus changing the blood pH and correcting imbalances. Excess acid or base is
then excreted in the urine by the renal system to control plasma bicarbonate concentration. Changes in
respiration occur primarily in minutes to hours, while renal function works to alter blood pH within several days.
Role in human health
Production of CO2 is a result of normal body metabolism. Exercise or serious infections will increase the
production of CO2 through increased respiration in the lungs. When oxygen (O2) is inhaled and CO2 is exhaled,
the blood transports these gases to the lungs and body tissues. The body's metabolism produces acids that are
buffered and then excreted by the lungs and kidneys to maintain body fluids at a neutral pH. Disruptions in
CO2 levels and HCO3-create acid-base imbalances. When acid-base imbalances occur, the disturbances can
be broadly divided into either acidosis (excess acid) or alkalosis (excess base/alkali).
Common diseases and disorders
Acid-base metabolism imbalances are often characterized in terms of the HCO3-/CO2 buffer system. Acid-base
imbalances result primarily from metabolic or respiratory failures. An increase in HCO3-is called metabolic
alkalosis, while a decrease in the same substance is called metabolic acidosis. An increase in PCO 2, on the
other hand, is known as respiratory acidosis, and a decrease in the same substance is called respiratory
alkalosis.
Acidosis
Acidosis is a condition resulting from higher than normal acid levels in the body fluids. It is not a disease, but
may be an indicator of disease. Metabolic acidosis is related to processes that transform food into energy and
body tissues. Conditions such as diabetes, kidney failure, severediarrhea, and poisoning can result in
metabolic acidosis. Mild acidosis is often compensated by the body in a number of ways. However, prolonged
acidosis can result in heavy or rapid breathing, weakness, and headache. Acidemia (arterial pH < 7.35) is an
accumulation of acids in the bloodstream that may occur with severe acidosis when the acid load exceeds
respiratory capacity. This condition can sometimes result in comaand, if the pH falls below 6.80, it will lead to
death. Diabetic ketoacidosis is a condition where excessive glucagon and a lack of insulin contribute to the
production of ketoacids in the liver. This condition can be caused by chronic alcoholism and poor
carbohydrate utilization.
Respiratory acidosis is caused by the lungs's failure to remove excess carbon dioxide from the body, reducing
What is Acidosis (Definition)
Acidosis is the result of our body pH becoming overly acid. The pH balance of our cells and internal fluids
can effect every process in our body. Of these fluids, the blood is perhaps the most important. In a similar
way that you body will do whatever it takes to regulate your body temperature, it will also do the same to
ensure a slightly alkaline pH in the blood.The body will literally go to whatever lengths necessary to
ensure that the blood retains this pH level, including wreaking havoc on other tissues, bodily functions
and systems (such as digestion, lymph and cardiovascular).

World renowned microbiologist Dr. Young states:"The pH level of our internal fluids affects every cell in
our bodies. The entire metabolic process depends on an alkaline environment. Chronic over acidity
corrodes body tissue, and if left unchecked will interrupt all cellular activities and functions, from the
beating of your heart to the neutral firing of your brain. In other words, over-acidity interferes with life
itself"

The human body needs to take in the right amount of acidic and alkalizing nutrients to
maintain a healthy pH balance. Your daily intake should be 20% acidic and 80%
alkalizing.

If this balance is not maintained, the body has to compensate in the following ways.

It first robs minerals from the bones, joints, muscles, gallbladder and mucousal lining
of the digestive track.

When the body robs calcium from the bones you can develop a weak back. If Ieft
untreated, this can develop into Osteoporosis (low bone density).

Robbing calcium and sodium from the joints can cause them to start to lock up, get
stiff, sore and/or crack. After a time, the immune system often attacks acid which
may settle in the joints. A doctor would probably diagnose this as "arthritis".

Minerals robbed from the muscles, ligaments, and tendons increase the likelihood of
an injury or tear. Acid deposited in the muscles can cause fibromyalgia, soreness
and/or stiffness. Minerals robbed from the heart muscle can cause weakening,
arrhythmia and angina.

If the body needs to rob minerals from the lining of the intestinal track, or if the body
tries to eliminate acid through the intestine, you could develop pain in the colon,
colitis, diarrhea, Crohn's or irritable bowel.

Natural sodium is often robbed from the lining of the esophagus. If enough erosion
happens, it can prevent the sphincter muscle at the top of the stomach from closing
properly, resulting in heartburn, acid reflux or GERD. Damage to the esophagus can
cause difficulty in swallowing or a narrowing of the esophagus.

To protect you, the body will try to eliminate acid through the bowel, kidneys, skin
and respiratory system.

Eliminating through the lungs (lower respiratory system) can cause asthma. If acid
settles in the sinuses (upper respiratory system), the body will try to dilute it with
mucus, which can result in post nasal drip or sinus problems.

Eliminating through the urinary system can cause blood in the urine and/or bladder
irritation, cystitis, and later on kidney damage. It can also increase the likelihood of
developing UTI's (Urinary Track Infections).

When the body's pH is acidic for a long period of time, it can start changing the
blood's pH from an ideal 7.41 to a more acidic 7.35, which can cause irritation and
inflammation in the arteries. In response to this, the body will line the arteries with
cholesterol to protect the arteries from the pH imbalance.

When the body gets to the point that it can no longer rob minerals safely, the body
will commission the liver to produce ammonia in order to help neutralize the acid.
This causes alkalinity or a pH above 7.0

Since Dr. Otto Warburg was awarded the Nobel Peace Prize in 1931 and 1946 for his
studies on how cancer can not thrive in an alkaline medium, people often think the
more alkaline the better. This is incorrect! Although acid burns the cells, alkalinity
poisons. Alkalinity mimics symptoms of acidosis. THE only way to know your pH
for sure is to test your saliva and urine with test strips.

To determine your saliva and urine pH, get test strips that are in increments of .5
(you can get them locally at most health stores. If you cannot find a retailer, you
can purchase them from me, but the shipping would cost more than the strips).

Following the directions that came with the strips, test your urine and saliva (using
a separate strip for each) first thing in the morning before you brush your teeth,
smoke a cigarette, chew gum or mints, drink or eat anything.

Often the liver loses its ability to produce ammonia and then cells are bathed in acidic
fluid. The body uses enzymes to break down abnormal cells in the body. Enzymes
cannot work in an acidic medium. Therefore, the body cannot protect you from the
growth of abnormal cells. This is why they say acid feeds cancer cells. More
accurately, it protects cancer cells from enzymes used by the immune system.
Without the enzymes to break up the cancer cells, the body can not eliminate them.

I believe it is wise to check your pH on a regular basis in hopes of reversing and

avoiding the health conditions which can be caused directly by a pH imbalance, such
as:

Lower back pain or Arthritis or Cracking, painful,

Osteoporosis
Weak lower back Rheumatism or stiff joints
Fibromyalgia Acid Reflux Heartburn GERD
Gallstones or
Crohn's or Colitis IBS Ulcers Gallbladder
problems
Cystitis (bladder Sinus problems
Lung problems Asthma
irritations) (mucus) drip
Plaque build up Malabsorption of
Cancer Skin problems
in arteries nutrients

What do I do if my pH is balanced?

I don't believe there would be a need for any supplements, but I would still follow the
80% alkaline and 20% acidic diet. I would also monitor my pH on a regular basis. I
personally do it every Monday morning because stress, diet, etc can cause a fluxuation
in the pH and knowing that, you can rebalance it, hopefully before any damage is
done to the tissues of the body.

What do I do if I am alkaline?

I would eat the pH balance diet to help build up the mineral reserves and take Nature's
Sunshine's Liquid Calcium. I suggest this calcium because it provides the body with
calcium to build up it's reserve, but was made acidic specifically for those who are
alkaline. So you get your calcium which is usually around 10 pH without adding to
your alkalinity.
Also, when people take the regular calcium and are alkaline, they get constipated or
do not feel well. Some even have their blood pressure spike.

What do I do if I am acidic?

If I had an acidic pH, I would GRADUALLY adjust my diet to the suggestions above,
cut out all tea and coffee and milk products (except butter).

There are some alkalizing herbs, but most of the balance has to be maintained by diet.
Herbs which promote correct pH are: Liquid Chlorophyll (approx pH 11.6); Skeletal
Strength; Herbal CA; Vitamin Calcium; Slippery Elm; and Parsley. My favorites are
Liquid Chlorophyl and Skeletal Strength.

Even a correct diet which is not digested well can ferment, causing gas, bloating and
acid. A lack of HCL (Hydrocloric Acid) produces the symptoms of burping... for this
I would suggest taking PDA.

A lack of digestive enzymes produces the symptom of bloating or flatulence

(farting)... for this I would suggest Proactazyme.

Food Enzymes contains both HCL and enzymes.

To remove acid from the body, I would suggest either Una de gato or Devil's Claw.

What should pH be?

I believe that your saliva pH should be 6.3 - 6.6 and the Urine should be 5.5 - 6.8.

Please remember, before you start any pH balancing program, take your saliva and
urine pH with pH testing strips. If an imbalance is profound, it can be very serious
and I would suggest soliciting the help of an alternative health professional to get the
pH back into balance.

pH
n chemistry, pH is a measure of the acidity or basicity of an aqueous solution.[1] Pure water is said to be neutral, with

a pH close to 7.0 at 25 °C (77 °F). Solutions with a pH less than 7 are said to be acidic and solutions with a pH

greater than 7 are basic or alkaline. pH measurements are important

in medicine, biology, chemistry, agriculture, forestry, food science,environmental science, oceanography, civil

engineering and many other applications.

In a solution pH approximates but is not equal to p[H], the negative logarithm (base 10) of the molar concentration of

dissolved hydronium ions (H3O+); a low pH indicates a high concentration of hydronium ions, while a high pH

indicates a low concentration. This negative of the logarithm matches the number of places behind the decimal point,

so, for example, 0.1 molar hydrochloric acid should be near pH 1 and 0.0001 molar HCl should be near pH 4 (the

base 10 logarithms of 0.1 and 0.0001 being −1, and −4, respectively). Pure (de-ionized) water is neutral, and can be

considered either a very weak acid or a very weak base (center of the 0 to 14 pH scale), giving it a pH of 7 (at
25 °C (77 °F)), or 0.0000001 M H+.[2] For anaqueous solution to have a higher pH, a base must be dissolved in it,

which binds away many of these rare hydrogen ions. Hydrogen ions in water can be written simply as H + or

ashydronium (H3O+) or higher species (e.g., H9O4+) to account for solvation, but all describe the same entity. Most of

the Earth's freshwater bodies surface are slightly acidic due to the abundance and absorption of carbon dioxide; [3] in

fact, for millennia in the past, most fresh water bodies have long existed at a slightly acidic pH level.

However, pH is not precisely p[H], but takes into account an activity factor. This represents the tendency of hydrogen

ions to interact with other components of the solution, which affects among other things the electrical potential read

using a pH meter. As a result, pH can be affected by the ionic strength of a solution—for example, the pH of a 0.05

M potassium hydrogen phthalate solution can vary by as much as 0.5 pH units as a function of added potassium

chloride, even though the added salt is neither acidic nor basic.[4]

Hydrogen ion activity coefficients cannot be measured directly by any thermodynamically sound method, so they are

based on theoretical calculations. Therefore, the pH scale is defined in practice as traceable to a set of standard

solutions whose pH is established by international agreement. [5] Primary pH standard values are determined by

the Harned cell, a hydrogen gas electrode, using the Bates–Guggenheim Convention.

pH in its usual meaning is a measure of acidity of (dilute) aqueous solutions only. [1] Recently the concept of "Unified

pH scale"[6] has been developed on the basis of the absolute chemical potential of the proton. This concept proposes

the "Unified pH" as a measure of acidity that is applicable to any medium: liquids, gases and even solids.

Definitions
[edit]Mathematical definition

pH is defined as a negative decimal logarithm of the hydrogen ion activity in a solution.[14]

where aH+ is the activity of hydrogen ions in units of mol/L (molar concentration). Activity has a sense of

concentration, however activity is always less than the concentration and is defined as a concentration (mol/L) of

an ion multiplied by activity coefficient. The activity coefficient for diluted solutions is a real number between 0

and 1 (for concentrated solutions may be greater than 1) and it depends on many parameters of a solution, such

as nature of ion, ion force, temperature, etc. For a strong electrolyte, activity of an ion approaches its

concentration in diluted solutions. Activity can be measured experimentally by means of an ion-selective

electrode that responds, according to the Nernst equation, to hydrogen ion activity. pH is commonly measured

by means of a glass electrode connected to a milli-voltmeter with very high input impedance, which measures
the potential difference, orelectromotive force, E, between an electrode sensitive to the hydrogen ion activity and

a reference electrode, such as a calomel electrode or a silver chloride electrode. Quite often, glass electrode is

combined with the reference electrode and a temperature sensor in one body. The glass electrode can be

described (to 95–99.9% accuracy) by the Nernst equation:

where E is a measured potential , E0 is the standard electrode potential, that is, the electrode potential for

the standard state in which the activity is one. R is the gas constant, T is the temperature in kelvins, F is

the Faraday constant, and n is the number of electrons transferred (ion charge), one in this instance. The

electrode potential, E, is proportional to the logarithm of the hydrogen ion activity.

This definition, by itself, is wholly impractical, because the hydrogen ion activity is the product of

the concentration and an activity coefficient. To get proper results, the electrode must becalibrated using

standard solutions of known activity.

The operational definition of pH is officially defined by International Standard ISO 31-8 as follows:[15] For a
solution X, first measure the electromotive force EX of the galvanic cell

reference electrode|concentrated solution of KCl || solution X|H 2|Pt

and then also measure the electromotive force ES of a galvanic cell that differs from the above one only

by the replacement of the solution X of unknown pH, pH(X), by a solution S of a known standard pH,

pH(S). The pH of X is then

The difference between the pH of solution X and the pH of the standard solution depends only on

the difference between two measured potentials. Thus, pH is obtained from a potential measured
with an electrode calibrated against one or more pH standards; a pH meter setting is adjusted

such that the meter reading for a solution of a standard is equal to the value pH(S). Values pH(S)

for a range of standard solutions S, along with further details, are given in

the IUPAC recommendations.[16] The standard solutions are often described as standard buffer

solution. In practice, it is better to use two or more standard buffers to allow for small deviations

from Nernst-law ideality in real electrodes. Note that, because the temperature occurs in the

defining equations, the pH of a solution is temperature-dependent.

Measurement of extremely low pH values, such as some very acidic mine waters, [17] requires

special procedures. Calibration of the electrode in such cases can be done with standard

solutions of concentrated sulfuric acid, whose pH values can be calculated with using Pitzer

parameters to calculate activity coefficients.[18]

pH is an example of an acidity function. Hydrogen ion concentrations can be measured in non-

aqueous solvents, but this leads, in effect, to a different acidity function, because the standard

state for a non-aqueous solvent is different from the standard state for water. Superacids are a
class of non-aqueous acids for which the Hammett acidity function, H0, has been developed.

[edit]p[H]

This was the original definition of Sørensen,[10] which was superseded in favour of pH in 1924.

However, it is possible to measure the concentration of hydrogen ions directly, if the electrode is

calibrated in terms of hydrogen ion concentrations. One way to do this, which has been used

extensively, is to titrate a solution of known concentration of a strong acid with a solution of known

concentration of strong alkali in the presence of a relatively high concentration of background

electrolyte. Since the concentrations of acid and alkali are known, it is easy to calculate the

concentration of hydrogen ions so that the measured potential can be correlated with

concentrations. The calibration is usually carried out using a Gran plot.[19] The calibration yieds a
value for the standard electrode potential, E0, and a slope factor, f, so that the Nernst equation in

the form

can be used to derive hydrogen ion concentrations from experimental measurements of E.

The slope factor is usually slightly less than one. A slope factor of less than 0.95 indicates

that the electrode is not functioning correctly. The presence of background electrolyte

ensures that the hydrogen ion activity coefficient is effectively constant during the titration. As

it is constant, its value can be set to one by defining the standard state as being the solution
 containing the background electrolyte. Thus, the effect of using this procedure is to make

activity equal to the numerical value of concentration.

The difference between p[H] and pH is quite small. It has been stated[20] that pH = p[H] +

0.04. It is common practice to use the term "pH" for both types of measurement

What is the pH Balance of the Body?

The pH level is one of the most important balance systems of the body. The termpH stands
for “potential” of “Hydrogen”. It is the amount of hydrogen ions in a particular solution. The
more ions, the more acidic the solution. The fewer ions the more alkaline (base) the
solution. The pH level is a measure of acidity or alkalinity, on a scale of zero to fourteen,
with zero being most acid, fourteen being most alkaline and seven being mid-range. The
most critical pH balance is in the blood.

Acidic Alkaline

Normal blood pH has a very small window of acid/alkaline pH balance. Blood pH must range
between 7.35 and 7.45. This means that there is an adequate amount of oxygen in the
blood. Any slight decrease in pH will result in lower oxygen levels in the blood
and, therefore, in the cells. Any drop in pH, no matter how slight, is the beginning of a
disease state and affects when and how we age. All other organs and fluids will fluctuate in
their range in order to keep the blood at a strict pH between 7.35 and 7.45 (slightly
alkaline). This process is called homeostasis. The body makes constant adjustments in
tissue and fluid pH to maintain this very narrow pH range in the blood. A normal pH of all
tissues and fluids of the body (except the stomach) is slightly alkaline. The stomach pH is
much more acid than the intestinal pH because the stomach needs an acid environment
(hydrochloric acid) to break down food for digestion. Whereas, the flora (good bacteria) of
the intestine need a more alkaline environment to assimilate and process the nutrients from
the foods digested by the stomach.
How Does Eating Affect Our pH Level?

Diet is probably the most important change we can make to balance our natural
pH. We need to eat at least 75% alkaline-forming foods. The average all-
American diet consists of about 80% acid-forming foods! Because processed and
refined foods are extremely acidic to our systems, the body creates a buffering
system (a chemical process to protect the body from being harmed by the acids).
This buffering process requires the use of many nutrients from the body, including
electrolyte minerals (organic potassium, magnesium, sodium, calcium, to name a
few). Electrolyte minerals are not minerals from the ground. They're minerals from
plant sources that have gone through the process of photosynthesis.

Testing pH - What is the normal pH of blood, urine, and saliva?

Pure water, which has pH of 7, is neutral. Substances with a pH less than 7 are considered
acidic and substances with a pH of greater than 7 are considered basic.

The normal pH of blood running through arteries (large elastic-walled blood vessels that
carry blood from the heart to other parts of the body) is 7.4; the pH of blood in the veins
(vessels that transports blood to the heart) is about 7.35. Normal urine pH averages about
6.0. Saliva has a pH between 6.0 and 7.4.

You can easily monitor your pH with simple testing strips which can be purchased at your
local pharmacy. Testing saliva is the easiest way to gauge the body’s pH. To test saliva:
Wait 2 hours after eating. Spit into a spoon. Dip the strip. Read immediately. Use the color
chart from the correct indication. An optimal reading is 7.5. This indicates a very slightly
alkaline body.

Urine is more acidic than saliva. To test urine: Test a urine sample first thing in the
morning. Fill a small cup with urine, and dip a strip into the cup. Read
immediately.An optimal reading is about 6.5

Source: Guyton, Arthur C. Textbook of Medical Physiology, 8th ed., pp. 331, 340, 711.

About Balancing the pH

There are many good products out there for raising pH levels. Your diet and water are most
important, however. Below are a few of our favorite ways for quickly raising pH levels and
oxygenating tissue.
The bicarbonate buffering system is an important buffer system in the acid-base
homeostasis of living things, including humans. As a buffer, it tends to maintain a relatively constant plasma pH and

counteract any force that would alter it.

In this system, carbon dioxide (CO2) combines with water to form carbonic acid (H2CO3), which in turn rapidly

dissociates to form hydrogen ion and bicarbonate (HCO3- ) according to the reactions below. The carbon dioxide -

carbonic acid equilibrium is catalyzed by the enzyme carbonic anhydrase; the carbonic acid - bicarbonate equilibrium

is simple proton dissociation/association and needs no catalyst.

Any disturbance of the system will be compensated by a shift in the chemical equilibrium according to Le

Chatelier's principle. For example, if one attemted to acidify the blood by dumping in an excess of hydrogen ions

(acidemia), some of those hydrogen ions will associate with bicarbonate, forming carbonic acid, resulting in a

smaller net increase of acidity than otherwise. This buffering system becomes an even more powerful regulator

of acidity when it is coupled with the body's capacity for respiratory compensation, in which breathing is altered

to modify the amount of CO2 in circulation. In the above example, increased ventilation would increase the loss

of CO2 to the atmosphere, driving the equilibria above to the left. The process could continue until the excess

acid is all exhaled.

This process is extremely important in the physiology of blood-having animals. It manages the many acid and

base imbalances that can be produced by both normal and abnormal physiology. It also affects the handling of

carbon dioxide, the constantly produced waste product of cellular respiration.

Protein buffering
The protein buffer system is part of the body's mechanism for controlling blood Hydrogen (H+) ion homeostasis.
Both intracellular and extracellular proteins have negative charges and can serve as buffers for alterations in
hydrogen ion concentration. However, because most proteins are inside cells, this primarily is an intracellular buffer
system. Haemoglobin (Hb) is an excellent intracellular buffer because of it's ability to bind with Hydrogen ions
forming a weak acid and carbon dioxide (CO2). After oxygen is released in the peripheral tissues, haemoglobin
binds with CO2 and H+ ions. As the blood reaches the lungs these actions reverse themselves. Haemoglobin binds
with oxygen, releasing the CO2 and H+ ions. The H+ ions combine with bicarbonate (HCO3) ionsto form carbonic
acid (H2CO3). The H2CO3 breaks down to form water (H2O) and carbon dioxide (CO2) which are excreted via
expiration through the lungs. Therefore respirations help maintain pH.