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At equilibrium
o A reaction with a decrease in enthalpy and an increase in entropy is spontaneous at all
temperatures.
2 law: energy tends to spread out
nd
Reduction, the gain of electrons is accomplished by the addition of hydrogen or the removal of oxygen.
The plant or animal that eats can then break down the monosaccharide to use it as fuel to power
other metabolic activities.
In the process the carbon is oxidized it loses electrons through the addition of oxygen or the removal of hydrogen
and ultimately becomes CO2.
The oxidation of carbon is thermodynamically favorable so it can be coupled to energy requiring
processes such as the synthesis of building blocks and their polymerization to form macromolecules
Mostly all metabolic processes occur with the aid of catalysts called enzymes which most are proteins
An organism with its high level of organization represents a state of low energy relative to its
surroundings. (high organization/stability= low energy)
the organism can maintain this thermodynamically unfavorable state as long as it continually obtains
free energy from its food when it exhausts food, G= 0 resulting in death
The Origin and Evolution of Life
the ability to replicate is one of the universal characteristics of living organisms
cells will carry out a set of instructions but will evolve throughout time
The first biological building blocks would have had to polymerize by gaining the capacity for self-replication.
Prokaryotes: small unicellular organisms that lack a discrete nucleus and usually contain no internal
membrane systems.
o This group is composed of two groups Archaea and eubacteria
Eukaryotes: cells usually larger than prokaryotic cells and contain a nucleus and other membrane bounded
cellular compartments. May be unicellular or multicellular.
o This group called the eukarya includes microscopic organisms as well as familiar macroscopic
plants and animals
o Eukaryotic cells exhibit characteristics exhibit characteristics of both bacteria and archaea
o Eukaryotic cells also contain organelles that are almost certainly the descendants of free living
cells
The number of sequence differences between two groups of organisms indicates how long ago they
diverged from a common ancestor.
Species with similar sequences have a longer shared evolutionary history than species with dissimilar
sequences
Chapter 2: Aqueous Chemistry
Water Molecules form Hydrogen Bonds
Water is 60% by mass in humans
Characteristics of water
o Tetrahedral Bent Geometry
o Polar; Partial negative and positive charges in oxygen and hydrogen
o In Ice forms lattices, bonds with 4 H2O molecules
o In water each bond is short, molecules flicker
o Many biomolecules have atoms (hydroxyl, carbonyl, amine, amide) that can Hydrogen Bond with
water.
Amphiphilic molecules experience both hydrophilic interactions and the hydrophobic effect
Amphiphilic molecules: have both hydrophobic and hydrophilic portions
Ex. Nonpolar hydrocarbon tail and a polar carboxylate head
Polar groups of amphiphilic molecules are oriented towards the polar solvent and are hydrated, nonpolar
groups aggregate due to the hydrophobic effect to form a spherical micelle.
Can form a sheet to form bilayers
Henderson-Hasselbach equation: relates pH of a solution to the pK of an acid and the concenctration of the
acid (HA) and its conjugate Base (A-)
[Base]
pH = pK + log
[Acid]
pK and pH convey protonation state
o At pH < 3.5, amino acids are protonated
Net Positive Charge (+1)
COOH and NH3+
o At 3.5 < pH < 9.0, carboxyl is deprotonated
Charge is neutral (0)
Zwitter Ions
o At pH > 9.0, both groups are deprotonated
Net negative charge (-1)
COO- and NH2
Rule of thumb: pH = pK +/- 1
o When [A] = 10[HA]
pH = pK + log (10) = pK + 1
o When [HA] = 10 [A-]
pH = pK log (0.1) = pK – 1
Buffers
When HCl is added to a weak acid in equilibrium with its conjugate base, pH does not change dramatically
because some added protons combine with the conjugate to reform the acid and will not contribute to
increase [H+]
Effective buffering capacity: generally within one pH unit of its (pK = +/- pH)
Chapter 4 Protein Structure
Protein: consists of one or more polypeptides (chains of polymerized amino acids)
Amino Acid: small molecule with an amino (NH3+), a carboxylate (COO-), and R-group
o R group (side chain): determines biological reactivity
20 Amino Acids
Hydrophobic Amino Acids
o Alanine (Ala, A) o Leucine (Leu, L)
o Valine (Val, V) o Isoleucine (Ile, I)
o Phenylalanine (Phe, F) o Methionine (Met, M)
o Tryptophan (Trp, W) o Proline (Pro, P)
Amino Acids are linked via condensation reaction (water molecule is eliminated)
o Peptide bonds: linkage of two amino acids to form a polypeptide
o Residues: amino acids within the peptide
o Can be broken/hydrolyzed via exo or endopeptidases
2. At pH = 5.0
Sample problem. Draw the structure of the peptide Gly-Lys in its fully protonated forms. Which ionic form
predominates at (a) pH = 1, (b) pH = 7, (c) pH = 13
These are both regular secondary structures: component residues have backbone conformations
that are the same from one residue to the next
Tertiary Protein Structure: 3D shape of entire polypeptide and spatial arrangement of all its side
chains
Overall folding of the peptide backbone, includes its regular and irregular secondary structures
o X-Ray Crystallography: determined protein structure (ex. myoglobin)
o Globular Proteins
Domain: polypeptide segment that has folded into a single structural unit with a hydrophobic core
Ion Pairs: form between oppositely charged side chains or N- and C- terminal groups
Strong electrostatic interaction
But doesn’t contribute much to protein stability; favorable free energy of electrostatic interaction is offset
by loss of entropy when side chains are fixed.
Zinc Fingers: structures of 20-60 residues with one or two Zn2+ ions
o Common in DNA-binding proteins
o Ideal ion for stabilizing proteins; can interact with ligands (S,N, or O) provided by amino acids and
only has one oxidation state
Protein Folding: begins with formation of secondary structures
In cell, a newly synthesized polypeptides folds as soon as it emerges from the ribosome; part of the
polypeptide may adopt its mature tertiary structure before entire chain is synthesized
o Denatured: chemically unfolded
Addition of highly soluble substances (ex. salts or urea) that interfere with
the hydrophobic effect causing unfolding of the proteins
o Renatured: refolding
Protein renaturation is NOT random; approaches the native structure (most stable tertiary
structure) through alternate pathways
Small elements of secondary structure form first then come together due to the
hydrophobic effect to produce a mass with a hydrophobic core; small rearrangements yield
the native structure
The information required for protein folding is all contained in the amino acid
sequence.
Quaternary Structure: spatial arrangement of polypeptide chains in a protein with multiple subunits
Two or more subunits oriented in 3D space
o Due to noncovalent interactions
Subunits vs. Domains
o Domains: single chain that can form a local 3D structure; folded polypeptide segments
Independent structural unit with a hydrophobic core
o Subunit: two or more separate chains in a protein that orient in 3D space to give quaternary
structures
Domain Subunits
These interactions give an opportunity for subunits to influence each other’s behavior/cooperativity;
regulates functions not possible in single-subunit proteins
Affinity chromatography: separation via the basis of high affinity of the protein of interest for specific
chemical groups
o Takes advantage of unique ability to interact with another molecule
o Ex. Isolation of Concanavalin A, which binds to glucose
Column has glucose to bind to ConA
High-performance liquid chromatography (HPLC): carried out in closed columns under high pressure
Protein structures determined by X-ray crystallography, electron crystallography and NMR spectroscopy
X-Ray crystallography: performed on samples of proteins that have been crystallized
o X-ray’s bombard and electrons in crystals scatter the x-rays to produce a diffraction pattern
o Trace the polypeptide backbone and discern general shapes
o Crystallized proteins retain some ability to move
Electron Crystallography: electron beams probe the protein’s structure
o Proteins do not have to be crystallized
o 3D structures can be reconstructed
Nuclear Magnetic Resonance (NMR) spectroscopy: takes advantage of atomic nuclei (hydrogen) to
resonate in an applied magnetic field
o Spectrum consists of peaks that are analyzed to reveal distances between two H atoms close or
covalently connected to other atoms in space
o Constructs a 3D model of the protein
Chapter 5: Protein Function
Proteins have various functions:
I. Transport: myoglobin transports oxygen throughout muscles; hemoglobin transports oxygen in
blood
II. Structural: actin forms microfilaments in cells; tubulin dimers constitute microtubules; keratin
filamines in animal hair; collagen is a major protein in connective tissue
III. Motor function: myosin interacts with actin to facilitate muscular movement
IV. Catalysis
V. Immunity
VI. Regulation of Gene Expression
𝐵𝑜𝑢𝑛𝑑 𝑀𝑏 [𝑀𝑏𝑂2]
Y= = [𝑀𝑏]+[𝑀𝑏𝑂2]
(fractional saturation)
𝑇𝑜𝑡𝑎𝑙 𝑀𝑏
Hemoglobin binding is sigmoidal because at low [O2], hemoglobin is reluctant to bind to the first
O2, but as the concentration (pO2) increases, O2 binding sharply increases
Indicates that the four heme groups in Hb are not independent and communicate cooperatively
Key physiological function: hemoglobin’s low oxygen affinity and cooperative binding behavior
In lungs, the pO2 is 100 torr – hemoglobin is 95% saturated with O2
In tissues, pO2 is 20-40 torr – hemoglobin is 55% saturation; Hb affinity decreases
o Here, O2 released by hemoglobin is readily taken up by myoglobin in muscle cells, since
myoglobin’s affinity for O2 is much higher at relatively low oxygen concentration.
(from lecture)
At 15 kPa (lungs) Hb 95% saturation - low ability to deliver/donate O2 at high [ ]
At 1-2 kPa (exercise) Hb 10% saturation – easier for Hb to deliver O2; myoglobin is source of O2
Erythropoietin (EPO) boosts red blood cell production
Synthesized by kidneys; individuals with kidney disease are deficient in EPO and develop anemia
o Treatment w recombinant EPO can increase red blood cell production
Can be abused by endurance sport athletes (like Lance Armstrong….smh)
Fetal hemoglobin has a higher O2 affinity than adult hemoglobin, which helps O2 transfer for maternal
circulation across the placenta to the fetus.
Chapter 6 How Enzymes Work
What is an enzyme?
There are three ways to increase the rate of a chemical reaction:
1. Increase the temperature (adding energy in the form of heat)
2. Increasing the concentrations of the reactants
3. Addition of a catalyst
Living systems use enzymes
Ribozymes are catalysts made of RNA (exception)
Chymotrypsin: a digestive protein that is synthesized in the pancreas and secreted into the small intestine
to break down dietary protein
Hydrolysis of polypeptides take place in a cleft between the two domains near the side chains of
three residues (His, Asp, Ser) called the active site.
Catalyzes hydrolysis of peptide bonds at 190 per second
o Rate enhancement of 108 to 1012.
Acts under mild conditions
Has a broad range of substrate specificity
o Catalyzes hydrolysis of peptide, amide, and ester bonds following Phe, Trp, and Try.
o P-nitrophenylacetate (an ester) is readily hydrolyzed by chymotrypsin.
The activities of enzymes are regulated in order to respond to changing conditions of follow genetically
determined developmental programs.
Enzyme Classification
I. Oxidoreductases = Oxidation-reduction reactions
II. Transferases = Transfer of functional groups
III. Hydrolases = Hydrolysis reactions
IV. Lyases = Group elimination to form double bonds
V. Isomerases = Isomerization reactions
VI. Ligases = Bond formation coupled with ATP hydrolysis
Overall: An enzyme lowers the height of the activation energy barrier (G++) by lowering the energy of the
transition state.
II. Covalent Catalysis (Nucleophilic Catalysis): a covalent bond forms between the catalyst and the
substrate during formation of the transition state
An electron rich group (nucleophile) in the enzyme active site forms a covalent adduct with a
substrate.
Undergoes a two-part reaction process, so there is two energy barriers.
Ser, Tyr, Cys, Lys, and His are often good covalent catalysts
Ex. Catalysis of acetoacetate to acetone via a primary amine (RNH2) to form an imine (Schiff base)
III. Metal Ion Catalysis: A zinc ion stabilizes a developing negative on the transition state
o Metal ions participate in enzymatic reactions by mediating oxidation-reduction reactions
o Or by promoting the reactivity of other groups in the enzyme’s active site through
electrostatic effects.
A protein-bound metal ion can also interact directly with the reacting substrate.
III. Portion of protein is gone; other part is covalently attached to Ser 195
C-term of cleaved peptide leaves N-term of the substrate (acyl
group) linked to enzyme
Newly exposed N-terminus
Enzymes stabilize the transition state by binding tightly to the transition state.
Noncovalent interactions form and release free energy, lowering G++
Stabilization (tight binding) of transition state occurs in addition to A-B, covalent, or metal ion catalysis.
Accomplished through close complementarity in shape and charge between active site and transition state
Electrostatic catalysis
: Non-aqueous active site allows more powerful electrostatic interactions between the enzyme and substrate
Water molecules are sequestered in the active site, allowing an enzyme to eliminate the energy barrier
imposed by the solvent molecules. (Reactions proceed quickly when no solvent molecules interfere)
Vmax: maximum reaction velocity; when [S] is very high, all the enzyme is in its ES form and approaches
maximum activity
o Vmax = k2[E]T
𝑉𝑚𝑎𝑥 [𝑆]
Equation: 𝑣0 =
𝐾𝑚 +[𝑆]
1 𝐾𝑚 1 1
=( ) +
𝑣0 𝑉𝑚𝑎𝑥 [𝑆] 𝑉𝑚𝑎𝑥
1. Multisubstrate Reactions
Most bisubstrate reactions are redox reactions or transferase reactions
2. Multistep Reactions
An enzyme-catalyzed reaction may contain many steps.
The meaning of Kcat is the same for single-step reactions.
Ex. Multistep transketolase reaction
3. Nonhyperbolic Reactions
Oligomeric enzymes with multiple active sites do not obey Michaelis-Menten rate equations
Allosteric Enzymes: presence of a substrate at one active site can affect the catalytic activity of other
active sites
Cooperative Behavior: occurs when enzyme subunits are structurally inked to each other so that a substrate-
induced conformational change in one subunit causes conformational change.
Allosteric/Regulatory Enzymes: composed of two or more
sub-units that undergo conformational change upon binding of a
ligand
For both catalysis AND regulation
display sigmoidal curve
Exhibit cooperativity
Binding at one active site can affect the catalytic activity of
other site
Enzyme Inhibition
2 classes of inhibitors: irreversible and reversible
Irreversible inhibitor: “Suicide Inhibitor” forms covalent bond or very strong non-covalent interaction with
the enzyme.
Enter the enzyme’s active site and begins a reaction, but cause an incomplete reaction and get stuck in the
active site.
Reversible Inhibition: results when a substance binds reversibly (noncovalently) to an enzyme to alter its
catalytic properties
Can easily combine with and dissociate from the enzyme and render it inactive
E+I EI
INCREASE Km
DOES NOT AFFECT Vmax
Can happen
simultaneously
Transition State Analogs: compounds that mimic the transition state to take advantage of the active
site; make better inhibition (competitive inhibition)
Noncompetitive inhibitors: do not compete towards the active site; binds to a site on the enzyme other
than the active site to elicit a conformational change that affects structure/chemical properties of the active
site
Affect Vmax
Does NOT affect Km
Mixed Inhibition: inhibitor binding to the enzyme alters its conformation in a way that affects both Vmax and
Km
Uncompetitive Inhibition: binds to the enzyme-substrate complex; inhibitor can bind after one substrate
has bound to prevent the reaction from continuing and yielding product.
Km decreases as
Vmax decreases
Chapter 11 – Carbohydrates
What are carbohydrates?
Carbohydrates (sugars or saccharides) have the generic formula (CH2O)n : n is greater or equal to 3.
They are formed from CO2 and H2O.
Roles include:
o Energy in diet – fuel molecules; glucose and fructose (immediate use), starch and glycogen
(chemical storage forms for future use)
o Mediating intercellular communication – in combination w proteins and lipids on cell surfaces;
informational markers for molecular recognition
Cell-cell recognition and signal transduction in glycoproteins and glycolipids
o Structural support (cell walls) – scaffolding for bacteria and plant cell wall; connective tissue;
exoskeletons
o Components of nucleic acids – structural role as ribose and deoxyribose; and are polar sites for
catalytic processes by RNA ribozymes.
Not interchangeable
Enantiomers- mirror images of eachother
Epimers- pair of stereoisomers
Glucose gets chair conformation and is made of = 64% 𝛽 anomer + 36% 𝛼 anomer
11-2 Polysaccharides
monosaccharides can are hooked together linked by glycosidic bonds
Only one anomeric carbon involved in the glycosidic bond (C1)
each -OH group can participate in a condensation rxn which permits different bonding arrangements and
allows for branching
Lactose
● major fuel source for newborn mammals
● broken down by 𝜷 − 𝒈𝒂𝒍𝒂𝒄𝒕𝒐𝒔𝒊𝒅𝒂𝒆 (𝒍𝒂𝒄𝒕𝒂𝒔𝒆)
● adults make little lactase, therefore inefficient in
digestion disaccharide
Galactose + Glucose → Lactose
Sucrose
Starch
𝛼 (1 → 4)
𝛼 (1 → 6)
Pectin
● highly hydrophilic due to -OH groups
● holds H2O
● gel-like characteristics
Lignin
NOT a polysaccharide
● heterogeneous
● aromatic compound lead to difficulty in characterization
● hydrophobic, few -OH groups present
● covalently links to hemicellulose ex. strength in cell walls
Bioconversion
All components in wood is a large amount of stored energy into other fuels
Ethanol
● stable
● storable
● transportable
Chitin 𝛽 (1 → 4) 𝑙𝑖𝑛𝑘𝑒𝑑 𝑟𝑒𝑠𝑖𝑑𝑢𝑒𝑠 𝑎𝑟𝑒 𝑔𝑙𝑢𝑐𝑜𝑠𝑒 𝑑𝑒𝑟𝑖𝑣𝑎𝑡𝑖𝑣𝑒𝑠
ex. N-acetylglucosamine
11-3 Glycoproteins
N-linked oligosaccharides
● undergo processing attached to glycoproteins
linked to an Asn side chain
● undergo processing- N-glycosylation begins while a
protein is being synthesized by a ribosome associated
with the rough ER. When the newly synthesized protein
leaves the ER and traverses the Golgi apparatus,
glycosidases and glycosyltransferases act on it
O-linked oligosaccharides
● built in Golgi Apparatus one glycosyltransferases
● tend to be large
● do NOT go undergo processing by glycosidases
● major component of mucus provides protective layer
for respiratory and digestive tracts
● undergo processing attached to glycoproteins linked
to Ser or Thr
Type A
oligosaccharides has terminal N-acetylated galactose group
● develop antibodies recognize and crosslink red blood cells bearing Type-B oligo.
● can receive Type-O
Type B
oligosaccharides has terminal galactose group
● develop antibodies recognize and crosslink red blood cells bearing Type-A oligo.
● can receive Type-O
Type O
oligosaccharides has none of these terminal groups (mutation- lacking final residue)
● develop antibodies recognize and crosslink red blood cells bearing Type-A or Type-B oligo.
● if A, B, or AB blood fusion is done antibodies will react with transfused cells causing lysis, clumping, or
blocked vessels
AB
● DO NOT develop antibodies recognize and crosslink red blood cells bearing Type-A or Type-B oligo.
Glycosaminoglycans
repeating disaccharides amino sugar N-acetylated and
uronic acid (sugar w/ carboxylate group)
Roles:
● in variably on the extracellular side of the plasma
membrane
● attract water (occupy the spaces between the cells
and extracellular matrix ex. collagen fibrils)
extracellular proteoglycan and glycosaminoglycan chains not connected to protein scaffold play a role in
connective tissue
Mechanical Pressure Squeezes H2O from glycosaminoglycans which allow accommodation to body
movements
● brings negative charged sulfate and carboxylate group of polysaccharide close together
● “shock absorption qualities” spring back repulsion between anionic group is relieved and water drawn
back into the molecule
Staphylococcus aureus
➢ glycans chains are perpendicular to cell surface
➢ honeycomb like
Box 11-C
Antibiotics
● inhibits synthesis of DNA, RNA, or proteins
Common role: disruption of cell wall synthesis
Penicillin (𝛽 − 𝑙𝑎𝑐𝑡𝑎𝑚 𝑎𝑛𝑡𝑖𝑏𝑖𝑜𝑡𝑖𝑐)
● first antibiotic used clinically
● inhibits enzyme that cross-link peptidoglycan, this weakening cell wall through disruption of osmotic
pressure
MRSA- Bacterias resistant to 𝛽 − 𝑙𝑎𝑐𝑡𝑎𝑚 produce enzyme that cleaves amide bond of 𝛽 − 𝑙𝑎𝑐𝑡𝑎𝑚 𝑟𝑖𝑛𝑔
Liver and Muscle tissue use monosaccharides to synthesize glycogen (the storage
polymer of glucose)
Short-term carbohydrates, lasts about 12 hours as a source of energy.
There is high concentration in liver and muscles.
Glycogen is highly branched, but compact. Therefore, several glycogen molecules
can clump to form granules.
Branching allows for quick addition or removal of glucose residues.
When glucose runs low, adipose tissue begins to mobilize its fat stores.
Lipase hydrolyzes triacylglycerols in order for fatty acid release into the
bloodstream.
These fatty acids are not water-soluble and can bind to circulating
proteins.
The body cannot budget burning fatty acids however, the heart uses fatty
acids as its primary fuel.
Cellular proteins are continuously degraded therefore, there are two major mechanisms for protein
degradation:
I. Degradation via the Lysosome (an organelle that contains proteases and hydrolytic enzymes)
o Breaks down proteins enclosed in a membranous vesicle.
o Membrane proteins and extracellular proteins are taken up
by endocytosis and are degraded
Metabolic Pathways
Metabolic pathways can be considered as: a series of intermediates or metabolites; a set of enzymes that
catalyze the reactions by which metabolites are interconverted; an energy-producing/requiring
phenomenon; or a dynamic process that can be turned up or down.
Major metabolic pathways share few common intermediates
A handful of metabolites appear as precursors or products in pathways that lead to all other types of
biomolecules.
Fatty acids have Methylene carbons and Carbohydrates (CH2O) have carbons that undergo oxidation.
Ubiquinone: a lipid-soluble electron carrier in which a membrane-associated enzyme transfers electrons from
a substrate to the electron carrier.
Ubiquinone can take up one OR two electrons (NAD+ is strictly a
two-electron carrier)
Reduced ubiquinol can diffuse through membrane and donate its
electrons.
The citric acid cycle generates considerable amounts of reduced cofactors that are recycled through oxidative
phosphorylation.
Reoxidation of NADH and QH2 and production of ATP
requires reduction of O2 and H2O
Overview of metabolism:
Monomers are formed.
Intermediates with two or three carbons are formed.
Carbons are fully oxidized to CO2.
Electron carriers gain electrons and are recycled via electron loss.
ATP and H2O are produced.
(from book)
Metabolic pathways are all connected
Pathway activity is regulated
Not every cell carries out every pathway
Each cell has a unique metabolic repertoire
Organisms may be metabolically interdependent.
Vitamin C: a cofactor for prolyl hydroxylase and lysyl hydroxylase, which are responsible for hydroxylation of
proline and lysine amino acids in collagen.
Hydroxyproline and hydroxylysine stabilize collagen by cross-linking the propeptides in collagen.
Deficiency (Scurvy): causes fragile capillary walls, easy bleeding of gums, loosened teeth, and bone-joint
diseases
Chapter 13 Glucose Metabolism
Biochemical Roles of Glucose
Source of metabolic energy
Precursor for the synthesis of structural polysaccharides (cellulose), disaccharides (sucrose and lactose)
and monosaccharides (galactose and fructose)
Primary
Control/Regulation point
of glycolysis
Irreversible Reaction
Slowest reaction in
glycolysis
PFK reaction is rate-determining reaction, which operates far from equilibrium and has a large negative free
change of energy and is irreversible under metabolic conditions.
Rate of reaction is altered by allosteric effectors, but NOT by fluctuations of concentration of substrates
and products.
Step 4: Aldolase
Converts fructose-1,6-bisphosphate to two three carbon molecules, Dihydroxyacetone phosphate and
glyceraldehyde-3-phosphate.
Products of the aldolase reaction are both phosphorylated, but only glyceraldehyde-3-phosphate
proceeds through the pathway
Oxidation-Reduction reaction
o NAD+ is reduced to NADH
o Aldehyde group of GA-3-P is oxidized
Substrate-Level Phosphorylation
Pyruvate can metabolize depending on the organism, type of cell, and intracellular conditions of the cell.
In oxygen-plentiful conditions: pyruvate is completely oxidized to CO2 and electrons are ultimately
transferred to O2
In oxygen-limited conditions: other molecules serve as electron acceptors to regenerate NAD +
Fermentation: extraction of energy from carbohydrates and other organic substrates without using oxygen as
an electron acceptor
a. Lactate Fermentation: anaerobic microorganism and
in muscle cells under limiting oxygen conditions
b. Ethanol fermentation: yeast and other
microogranisms.
Yeast Fermentation
Sugars are transformed to pyruvate via glycolysis
Then, pyruvate decarboxylase removes carboxylate group
on pyruvate to produce acetaldehyde
Alcohol dehydrogenase then reduces acetaldehyde to ethanol.
Alcohol metabolism
The liver can metabolize ethanol, which is readily absorbed in the GI tract and transported by the blood
stream.
Alcohol dehydrogenase converts ethanol to acetaldehyde
Then, acetaldehyde is converted to acetate via acetaldehyde hydrogenase.
Both require NAD+ as a cofactors.
Shortage of liver NAD+ slows fatty acid breakdown and promotes fatty acid synthesis
Further catabolism of pyruvate is initiated via decarboxylation
to form a two-carbon acetyl group linked with coenzyme A
Acetyl-CoA is a substrate for the citric acid cycle.
Gluconeogenesis
The liver can synthesize glucose from non-carbohydrate precursors via gluconeogenesis.
Kidneys can perform gluconeogenesis (limited) when glycogen supply in liver is exhausted.
It is the reverse of glycolysis: conversion of two molecules of pyruvate to one molecule of glucose.
Gluconeogenesis bypasses pyruvate kinase, phosphofructokinase, and hexokinase.
Instead four enzymes are used in this pathway:
o Hexokinase (in glycolysis) Glucose-6-Phosphatase (in gluconeogenesis)
o Phosphofructokinase (in glycolysis) Fructose bisphosphatase
o Pyruvate kinase (in glycolysis) Phosphoenolpyruvate carboxykinase & Pyruvate carboxylase
Pyruvate cannot be directly converted to phosphoenolpyruvate (pyruvate kinase catalyzes irreversible
reaction – step 10 in glycolysis)
1. Pyruvate is first carboxylated by pyruvate
carboxylase to yield oxaloacetate (this utilizes ATP.
2. Oxaloacetate is then decarboxylated via
phosphoenolpyruvate carboxykinase to form
phosphoenolpyruvate.
Alanine and Glutamine) are the main sources of precursors for gluconeogenesis because they can be
converted to oxaloacetate and then to phosphoenolpyruvate.
During starvation, proteins are broken down and are used to produce glucose to fuel the CNS.
Glycogenolysis
Glycogen is phosphorolyzed to yield glucose-1-phosphate.
In liver – phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate, then glucose-6-
phosphatase hydrolyzes the release of free glucose from glucose-6-phosphate
The need for NADPH can be greater in other reactions – excess carbons are recycled into intermediates for
glycolysis for degradation into pyruvate or for use in gluconeogenesis.
Enzymes such as transketolase and transaldolase – transfer 2/3C units among intermediates to produce
three to seven carbon sugars.
Ex. Transform 5C-Ribulose into 6C-units (fructose-6-phosphate) and 3C-unites (glyceraldehyde-3-
phosphate)
Chapter 14 – The Citric Acid Cycle
Beri-Beri Disease: Nutritional disease caused by the deficiency of thiamine (Vitamin B1)
The activated form of B1 is thiamine pyrophosphate (TPP), which is a coenzyme that assists enzymes
involved in decarboxylation.
Vitamin B1 (Thiamine) is a precursor for thiamine pyrophosphate, a cofactor used by the pyruvate
dehydrogenase complex (PDH)
It is also a co-factor for -ketoglutarate dehydrogenase
And is also found in a variety of foods such as meat and grains.
Decarboxylation reactions occur as pyruvate is further oxidized in the TCA,
therefore TPP-B1/Thiamine is a required cofactor for decarboxylase.
Preliminary Phase
The citric acid is central metabolic pathway whose starting material is 2C-acetyl units derived from amino-
acids, monosaccharides, and fatty acids. These are oxidized to waste product CO2, with the reduction of
cofactors: NAD+ and ubiquinone (Q)
Pyruvate is the starting point of the citric acid cycle (end product of glycolysis)
The pyruvate dehydrogenase complex directs conversion of pyruvate to acetyl CoA – this is the bridge
between glycolysis and aerobic metabolism
Pyruvate (3C) Acetyl CoA (2C) + NADH + CO2 Cytosol Mitochondria
Coenzyme A (CoA) has Vitamin B5 – they help the body convert food (carbohydrates) into fuel (glucose),
which is used to produce energy. These B vitamins are referred to as B complex vitamins, which also help the
body use fats and proteins.
The energy stored in the
thioester bond drives the
thermodynamically
unfavorable reactions.
Overview
Acetyl-CoA is derived from pyruvate and is a product of amino
acid catabolism (carbon skeletons of amino acids are broken
down to pyruvate)
Acetyl-CoA is a direct product of degradation of certain amino
acids and of fatty acids
For each acetyl group, two molecules of fully oxidized CO2 are
produced – loss of 4 pairs of electrons.
These electrons are transferred to 3NAD+ and ubiquinone
to produce 3 NADH and 1 QH2.
The free energy of the reaction is highly exergonic, citrate synthase has a free energy equivalent to breaking
the thioester bond of Acetyl-CoA
Reaction 2: Aconitase
Catalyzes the reversible isomerization of citrate to isocitrate
The reaction intermediate is Aconitate.
There is a
push via a
3 alcohol
group
Reaction 4: -ketoglutarate dehydrogenase
Releases the 2nd CO2 – catalyzes an oxidative decarboxylation reaction,
transferring the remaining 4-carbon fragment to CoA
-ketoglutarate dehydrogenase is a multienzyme complex that
resembles the PDH complex in structure/mechanism; E3 is the same
enzyme in both complexes
Isocitrate dehydrogenase
Inhibited by NADH
Activated by ADP and Ca2+
-ketoglutarate dehydrogenase
Inhibited by NADH and Succinyl-CoA
Activated by Ca2+
Citrate and pyruvate can cross the mitochondrial membrane via specific
transport proteins
This allows carbon atoms from mitochondrial Acetyl-CoA to be
transferred to the cytosol for fatty-acid/cholesterol synthesis
o Acetyl-CoA activates pyruvate carboxylase so that more oxaloacetate is produced when there is low
TCA activity and accumulation of Acetyl-CoA
There is normally low oxaloacetate concentration because the malate dehydrogenase reaction
is thermodynamically unfavorable
o The replenished oxaloacetate is converted to citrate, isocitrate, -ketoglutarate, etc.
The TCA cycle is a catalyst, therefore increasing concentrations of its components increases the flux through
the pathway.
During vigorous exercise, the concentration of TCA intermediates increases 3 to 4-fold in a few minutes to
help increase the energy-generating activity of the TCA cycle.
There is also an increased activity of the TCA regulatory enzymes (citrate synthase, isocitrate
dehydrogenase, and -ketoglutarate dehydrogenase) which increases the flux 100-fold
Some glutamate can be converted to -ketoglutarate to boost activity of the TCA cycle
Chapter 15 – Oxidative Phosphorylation
Oxidation of reduced compounds (NADH, FADH2/QH2) in the ETC coupled to ATP
synthesis.
Oxidation is spontaneous and energy released is conserved in a proton gradient.
Protons are pumped from the matrix to the intermembrane space.
Electrons flow spontaneously from substances with low to high reduction potential (from negative to a more
positive reduction potential)
Ex. The ’ for NAD+ (-.315V) is lower than in ubiquinone (0.045V), therefore NADH will tend to transfer its
electrons to ubiquinone (NADH is oxidized, Q is reduced)
Increase reduction potential = increase
electron affinity
The larger the difference in reduction
potential the change in free energy = more
spontaneous
Mitochondrial Electron Transport
Electrons are shuttle from NADH to O2 in a multistep process that offers several opportunities to conserve the
free energy of oxidation
Outer membrane- very porous, permits the transmembrane diffusion of substances with masses up to
about 10 Kd
Composition of the matrix differs from the intermembrane space
Ionic composition of the intermembrane space is equivalent to the cytosol due to the
presence of the porins in the outer membrane
The relatively impermeable inner mitochondrial membrane encloses the protein-
rich matrix – prevents the transmembrane movements of ions and small
molecules.
Individual mitochondria can move around the cell and undergo fusion and fission
Mitochondria also need a mechanism to export ATP and to import ADP and Pi
Adenine nucleotide translocase exports a ATP and imports ADP, binding one or the other and changing its
conformation to release the bound nucleotide on the other side of the membrane
Pi is imported from the cytosol in symport with H+
The protein complexes that carry out ETC and ATP synthesis are oriented in the inner mitochondrial
membrane so that they can bind the NADH
As electrons are transferred from NADH to Q, Complex I transfers 4 H+ from the matrix to the intermembrane
space
Each proton passes from one side of the membrane to the other via a proton wire
Proton wire - series of hydrogen-bonded protein groups plus water molecules that form a chain through
which a proton can be relayed
Proton taken up from the matrix are not the same ones that are released into the intermembrane space
Cystolic NADH can also go straight to Q (skeletal and brain), where it would only yield 1.5 ATP because 6 H+
are pumped into the inner membrane space (mitochondrial G-3-P dehydrogenase)
G-3-P dehydrogenase is embedded in the inner membrane
C1 = 4 H+, C3 = 4 H+, C4 = 2 H+
Flow of electrons through Complex III is complicated – two electrons donated by ubiquinol must split up to
travel through a series of one-electron carriers that include cyt c1 and cyt b
C3 has two active sites where Quinone cofactors undergo reduction and oxidation
Q cycle Net Result
Two electrons from QH2 reduce two molecules of cytochrome C
Four protons are translocated to the intermembrane space: 2 from QH2 in the first round of the Q cycle and
two from QH2 in the second round
Chemiosmosis
E from the H+ concentration gradient is used to make ATP via ATP synthase
Energy is conserved in proton gradient during ETC
Intermembrane space has a higher H+ concentration (lower pH)
Matrix has a lower H+ concentration (higher pH)
For a gradient to be created, ETC required
For ATP synthase to function, need H+ gradient
Proton wires: where H+ travel from matrix to intermembrane space (endergonic) overall spontaneous
Chemiosmotic Theory: proton translocating activity of ETC complexes in the inner mitochondrial membrane
generates a proton gradient across the membrane
Protons cannot diffuse back into the matrix because the inner membrane is impermeable to ions
Proton motive force- the imbalance of protons represents a source of free energy; this can drive the
activity of ATP synthase
The imbalance of protons, a nonequilibrium state, has an associated free E the force that would restore the
system to equilibrium)
Proton gradient has 2 components: reflecting the difference in the concentration of the chemical species
and the difference in electrical charge of the positively charged protons = electrochemical gradient
Matrix is more negative and intermembrane is more positive
10 protons translocated from the matrix to the intermembrane space is 200 kJ; therefore, going back it
would be -200 kJ, which is enough to drive the phosphorylation of several molecules of ADP
ATP synthase
F1 (matrix) component has 3 alpha and 3 beta subunits surrounding a central shaft; only the beta serves
catalytic role; catalytic subunit
F0 (integrated in membrane) includes and A and two b subunits that extent upward to interact with the F1
component and a ring of c subunits; channel for H+
Mitochondrial ATP synthase has 8 c subunits
Proton transport through ATP synthase involves the rotation of the c ring pass the stationary a subunit
3H+ needed to make one ATP, full rotation makes 3 ATP
A c subunit can take a proton from the intermembrane space
A slight rotation of the c ring brings another c subunit into position so that it can release its bound proton
into the matrix
All six subunits of F1 can bind adenine nucleotides, only beta subunits have catalytic activity
The alpha/beta hexamer change their conformations as the y subunit rotates (like a shaft driven by the c
ring “rotor”)
The binding change mechanism explains how ATP is made
ATP synthase uses mechanical energy to form a chemical bond (converts mechanical
to chemical energy)
The interaction between the y subunit and the alpha/beta hexamer explains this
energy transduction
Rotation-induced conformational change drives unfavorable ATP synthesis reaction
Binding change mechanism- rotation-driven conformational changes alter the affinity
of each catalytic beta subunit for an adenine nucleotide
At any moment, each catalytic site has a different conformation (and binding affinity),
referred to as the open, loose, or tight state
1. The substrates ADP and Pi bind to a beta subunit in the loose state
2. The substrates are converted to ATP as rotation of the y subunit causes the beta subunit to shift to the
tight conformation
3. The product ATP is released after the next rotation, when the beta subunit shifts to the open
conformation
Because the three beta subunits of ATP synthase act cooperatively, they all change their
conformation simultaneously as the y subunit turns
A full rotation of 360 degrees is required to restore the
enzyme to its initial state, but each rotation of 120 degrees
results in the release of ATP from one of the three active
sites
In the absence of a proton gradient, no ATP is synthesized
because there is no free E to drive the rotation of the y
subunit
Functions of lipids:
1. Energy Metabolism: long term storage energy - non-polar lipids
2. Components of biological membranes – polar lipids with nitrogen
and phosphate
3. Precursor of hormones – steroid class represented by cholesterol
4. Light absorbing pigment, electron carrier, signal molecules
Terpenes
Waxes (produced by plants on surfaces of leaves and fruits)
In humans, derivative of Arachidonate (C-20): signaling molecules that regulate blood pressure, pain and
inflammation.
All molecules derived from isoprene.
Provides odors and colors in plants.
More energy from fats; cardiac muscle use 95% energy from fatty acids
There is a higher energy of fatty acids because there are more reduced; more
oxidation; more ATP
What is the source of lipids that accumulate in vessel walls? They are deposited by the lipoprotein, LDL.
Lipoproteins are made of phospholipids, can travel through bloodstream because of polar heads and proteins
Lipids are in the core
The density of lipoproteins are dependent on protein content and also differ in diameter
o Chylomicrons are the largest (least dense)
o HDL are the smallest (densest)
Lipoproteins are the primary form of circulating lipid
Dietary lipids travel from the intestine to other tissues as chylomicrons via the lymphatic system
The main function of chylomicrons is to transport dietary TAG to adipose tissue and cholesterol to the liver
The liver repackages the cholesterol and other lipids (TAG, phospholipids, cholesteryl esters) into VLDL
VLDL give up TAG to the tissues, becoming smaller, denser, and richer in cholesterol and cholesteryl esters
IDL becomes LDL
Lipoproteins carry TAGs to tissues where hydrolysis releases their fatty acids from the glycerol backbone
The hydrolysis of TAG occurs extracellularly, catalyzed by lipoprotein lipase
TAG that are stored in adipose tissue are mobilized by an intra-cellular hormone sensitive lipase
Mobilized fatty acids travel through bloodstream bound to albumin
(66 kD protein that accounts for half the serum protein, bind metal ions and hormones, serves as an all-
purpose transport protein)
The concentration of free fatty acids in the body is very low because these molecules are detergents and can
disrupt cell membranes
High glucose = insulin
To be oxidatively degraded, a fatty acid must be activated
Low glucose = glucagon, and epinephrine
TAG activation requires 2 ATP equivalents, so we have to subtract 2 to achieve ne
Activated fatty acids are acylated to CoA
TAG activation occurs in the cytosol
Acyl-CoA requires a transporter into mitochondria, carnitine acyl transferase (inhibited by malonyl-
CoA)
Cytosol into the mitochondria
Beta Oxidation
Beta oxidation is a spiral pathway that has 4 enzymatic steps;
Each saturated fatty acid produces 1 NADH, 1 FADH2 (QH2), 1 Acetyl-CoA, an Acyl-CoA that is 2 C shorter
Each Acetyl-CoA produced goes into the TCA cycle where 3 NADH, 1 FADH2, 1 ATP are produced
Beta oxidation feeds directly into the ETC to produce ATP (NADH, FADH2 go into the ETC)
Total ATP produced is 14 ATP from one round of beta oxidation (12 ATP net because 2 consumed in activated
in cytosol)
Rounds of beta oxidation: #C / 2 – 1
Beta oxidation occurs on the beta C, third carbon; the two carbons receding the beta C are removed during
each round
The steps of a beta oxidation round:
Oxidation (produce FADH2)
Hydration (enoyl-CoA hydratase)
Oxidation (produce NADH) (Dehydrogenation)
Cleavage (2 C at a time)
This is why unsaturated fatty acids are not as fattening, because they do not
produce as much ATP
Compounds with double bonds are more oxidized than saturated
compounds, so less energy is released in converting them to CO2
The enoyl-CoA isomerase bypasses the QH2 producing acyl
dehydrogenase step (1.5 fewer ATP)
NADPH dependent reductase consumes 2.5 consumes 2.5 ATP
Electrons removed from Acyl-CoA are transferred from FADH2 to H2O2 instead of ubiquinone
FADH2 does not form ATP
Fatty acid oxidation is different than in peroxisomes
Peroxisome catalase breaks down hydrogen peroxide
The peroxisome serves as a chain shortening system because it has low affinity for short chains and high
specificity for long chains – peroxisomes break down fatty acids unrecognized by mitochondrial enzymes
Peroxisomes also degrade branched fatty acids (such as phytanate, which is from chlorophyll)
Phytanate must be degraded by the peroxisome
because because the methyl group at C3 prevents
dehydrogenation by 3—hydroxyacyl-CoA
dehydrogenase (step three of standard beta oxidation)
Deficiency in phytanate-degrading enzymes results in Refsum’s disease, a degenerative neural disorder
characterized by the accumulation of phytanate in the tissues
Packaging several enzyme activities into one multifunctional protein like mammalian fatty acid synthase allows
the enzymes to be synthesized and controlled in a coordinated fashion
The product of one reaction can quickly diffuse to the next acid site
Desaturases introduce double bonds into saturated fatty acids; take place in
the ER
Electrons removed in dehydrogenation of fatty acid are transferred to O2 to
produce H2O
Most common unsaturated fatty acids in animals are palmitoleate (C16)
and oleate (C18); both with one cis double bond at the 9,10 position
Trans fatty acids are relatively rare in plants and animals
Elongation can follow desaturation (and vice versa) – animals can synthesize a variety of fatty acids ,
HOWEVER, mammals cannot introduce double bonds at positions beyond C9
Cannot synthesize fatty acids such as linoleate and linolenate (are precursors of arachidonate (C20) and
other lipids with specialized biological activities)
Mammals must obtain linoleate and linolenate from their diet
Essential fatty acids are abundant in fish and plant oils
Omega-3 fatty acids- unsaturated fatty acids with a double bond three carbons from the end, may have
health benefits (deficiency from very-lowfat diet may cause slow growth/wound healing)
Acetoacetate and 3-hydroxybutyrate (ketone bodies) are synthesized from Acetyl-CoA in liver mitochondria
by the process, Ketogenesis.
Because it uses fatty acid-derived acetyl
groups, it helps spare amino acids that would
be diverted to gluconeogenesis
Ketone body synthesis occurs in the liver
mitochondria
Liver does not use ketone bodies, however
they donate synthesized ketone bodies,
missing 3-ketoacyl-CoA transferase
Assembly of ketone bodies is somewhat
reminiscent of the synthesis of fatty acids or
the oxidation of fatty acids in two-carbon steps
Ketone bodies are transported in the bloodstream without specialized lipoproteins because they are small and
water-soluble – easily pass through CNS
High ketogenic activity (such as in diabetes), ketone bodies are produced faster than they are consumed.
Excess acetoacetate breaks down to acetone - sweet breath is characteristic of acetone
Ketone bodies are acidic, leading to a drop in blood pH – ketoacidosis
Ketone bodies produced by the liver are used by other tissues as metabolic fuels after being converted back to
Acetyl-CoA
The liver itself cannot catabolize ketone bodies because it lacks 3-ketoacyl-CoA transferase
The fundamental similarity between phospholipid and triacylglycerol is the glycerol backbone
Cells must obtain cholesterol from circulating lipoproteins, but since mevalonate is also the precursor of
other isoprenoids such as ubiquinone, the long-term use of statins can have negative side effects
Cholesterol affects membrane fluidity
Cholesterol packaged in lipoprotein
High-density lipoproteins (HDL) are essential for removing excess cholesterol from cells
The efflux of cholesterol requires the close juxtaposition of the cell membrane and an HDL particle as well
as specific cell-surface proteins
Such as the ABC transporter that acts as a flippase to move cholesterol
from the cytosolic leaflet to the extracellular leaflet, from which it can
diffuse into the HDL particle
o Defect in the gene for the transporter cause Tangier disease which is
characterized by accumulating of cholesterol in tissues and a high risk
of heart attack
Because cells do not break down cholesterol and because the accumulation of cholesterol is potentially toxic,
the body must coordinate cholesterol synthesis and transport among tissues
Cholesterol shuts down its own synthesis by inhibiting the synthesis of enzymes such as HMG-CoA
reductase
Cellular cholesterol also represses transcription of the gene for the LDL receptor
Cholesterol metabolism in many cells is characterized by a balance between influx and efflux
o Fatty acid metabolism has two opposing pathways of synthesis and degradation that operate in
balance to meet the cell’s needs
Chapter 18 – Nitrogen Metabolism
Incorporation of ammonium ion into biological molecules
80% of air is Nitrogen (N2) and must be fixed (Fixed Nitrogen): Nitrite, Nitrate, and Ammonia
Nitrogenase: enzyme that carries out reduction of N2 into NH3 (Nitrogen Fixation)
Is a metalloprotein containing Fe-S clusters and Fe-Mo Cofactor (Molybdenum, Iron, Sulfur)
Ammonia exists in protonated form (NH4+)
Nitrogen fixing bacteria such as marine cyanobacteria and bacteria colonize root nodules of legumes
Ultimate sources of essential amino acids (must be obtained from food) are from plants and
microorganisms
Nonessential Amino Acids (can be synthesized): Ala, Arg, Asn, Asp, Cys, Glu, Gln, Gly, Pro,
Ser, Tyr
Essential Amino Acids (must be obtained): His, Ile, Leu, Lys, Met, Phe, Thr, Trp, Val
Tetrahydrofolate: a carrier of one-carbon units in several reactions of amino acids and nucleotide metabolism.
Mammals cannot synthesize folate and must be
obtained from diet
o Requirement for folate increases during
first few weeks of pregnancy for
development of fetal nervous system;
prevents neural tube defects such as
spina bifida
Serine is derived from 3-phosphoglycerate (3-
PG, from glycolysis) and can give rise to Glycine
via serine hydroxymethyl transferase
Amino acids with sulfur, branched chains, or aromatic groups are more difficult to synthesize
: Amino acids include Met, Cys, Tyr, Trp, His, Ile
Ser Cysteine
(Bacteria) (Humans)
High levels of homocysteine in blood is associated with homocystinuria (excess homocysteine is excrete)
Individuals develop atherosclerosis in children, homocysteine directly damages blood vessel walls
The synthesis for the Aromatic Amino Acids (Phenylalanine, Tyrosine, and Tyrptophan) begin with
condensation of Phosphoenolpyruvate (3-C, glycolysis) and Erythose-4-phosphate (4-C, PPP)
The 7 carbon reaction produce cyclizes and is modified to become
chorismate
Animals do no synthesize chorismate pathway is a target for
agents that inhibit plant metabolism without affecting animals
Nucleotide Biosynthesis
Nucleotides are synthesized from precursors that include amino acids
*Why don’t humans require purine and pyrimidines in their diet?
IMP is the substrate for the pathway that yield AMP and GMP
GTP participates in AMP synthesis: amino group from
aspartate is transferred to purine
ATP participates in GMP synthesis: glutamate is source of
amino group
Ribonucleotide reductase, followed by kinase phosphorylation generates dATP, dCTP, dGTP, and dUTP
dUTP is not used for DNA synthesis it is rapidly converted to thymine nucleotides
Thymine nucleotides help prevent accidental incorporation of uracil into DNA
dUTP is hydrolyzed to dUMP, then thymidylate synthase adds methyl to dUMP to produce dTMP using
methylene-tetrahydrofolate as one-carbon donor
Main source of methylene-tetrahydrofolate: serine hydroxymethyltransferase reaction (serine to glycine)
Thymidylate synthase oxidizes tetrahydrofolate to dihydrofolate
Dihydrofolate reductase (NADPH-dependent enzyme) then regenerates tetrahydrofolate cofactor
dTMP is then phosphorylated to dTTP – substrate for DNA polymerase
In cancer cells that undergo rapid cell division, thymidylate synthase and dihydrofolate reductase are highly
active
Compounds that inhibit these reactions are anti-cancer agents
Methoxetrate (an antifolate) is a competitive inhibitor of dihydrofolate reductase because they compete
for binding
o In presence of methoxetrate, Cancer cells cannot regenerate tetrahydrofolate required for dTMP
production and cell dies
Nucleotide degradation produces uric acid or amino acids
Nucleotides from food or from synthesis by cells can be broken down to release ribose groups and
purine/pyrimidine that can:
Be further catabolized and excreted (purines)
Or be used as metabolic fuel (pyrimidines)
At some points in degradation pathways, intermediates can be redirected towards synthesis of new
nucleotides by salvage pathways
The phosphorylated ribose can be catabolized or salvaged via conversion to 5-PRPP for synthesis of another
nucleotide – fate of base depends on whether purine or pyrimidine:
I. Purine base catabolism: purines are eventually converted into Uric Acid
Other organisms may further catabolize urate to generate Urea or
Ammonia
May require deamination and oxidation – depends if base was adenine,
guanine or hypoxanthine
Generates a waste produce that is excreted from the body
II. Pyrimidine base catabolism: cytosine, thymine, and uracil undergo deamination and reduction to open
the pyrimidine ring and further catabolism of these produces the amino acids:
-alanine (from cytosine and uracil) or -aminoisobutyrate (from thymine)
Contributes to the pool of metabolites for anabolic and catabolic processes
Cysteine can be converted into pyruvate that releases ammonia and sulfur
Degradation for Branched-chain AA’s (Val, Leu, Ile) and Aromatic AA’s (Phe, Tyr, and Trp) are more
complicated
Ile yields succinyl-CoA and acetyl-CoA
Leu yields acetyl-Aoa and acetoacetate (ketone body)
Lysine yields Acetyl-CoA and acetoacetate (different pathway from branched AA’s)
Met yields succinyl-CoA
Phe, Tyr and Trp yield acetoacetate (Ketone Body)
Approximately 80% of the body’s excess nitrogen is excreted in the form of Urea
*How are amino groups for amino acids incorporated into urea?
Glutamate supplies nitrogen to the urea cycle
Glutamate is deaminated to regenerate -ketoglutarate and release NH4+ via glutamate dehydrogenase
Many transaminases use -ketoglutarate as amino group
acceptor – glutamate is abundant
Only known enzyme that can use NAD+ or NADP+ as a cofactor
Major route for feeding AA-derived amino groups into urea cycle
Is subject to allosteric activation/inhibition
The starting substrate for the urea cycle is an activated molecule produced from the condensation of
bicarbonate and ammonia via carbamoyl phosphate synthetase
The carbamoyl phosphate synthetase and glutamate dehydrogenase reaction are combined with the
reactions of the Urea cycle are combined
Overall effect: transaminated AA’s donate amino groups via glutamate and aspartate to urea synthesis
Amino acids can be disposed via two routes:
1. Carb
2. Glu
Bacteria, fungi, and other organisms use urease to break down urea.
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