Human Anatomy & Physiology, 7th Edition, Chapter 24 Page 1 of 4

Metabolism

Overview
Once inside body cells, nutrients become involved in an incredible variety of biochemical reactions known collectively as metabolism (metabol = change).
During metabolism, substances are constantly being built up and torn down. Cells use energy to extract more energy from foods, and then use some of
this extracted energy to drive their activities. Even at rest, the body uses energy on a grand scale.

Anabolism and Catabolism

Metabolic processes are either anabolic (synthetic, building up) or catabolic (degradative, tearing down). Anabolism (ah-nabo-lizm) is the general term for
all reactions in which larger molecules or structures are built from smaller ones; for example, the bonding together of amino acids to make proteins.
Catabolism (kah-tabo-lizm) refers to all processes that break down complex structures to simpler ones, one example being hydrolysis of foods in the
digestive tract. In the group of catabolic reactions collectively called cellular respiration, food fuels, particularly glucose, are broken down in cells and
some of the energy released is captured to form ATP, the cells energy currency. ATP then serves as the chemical drive shaft that links energy-releasing
catabolic reactions to cellular work.
Recall from Chapter 2 that reactions driven by ATP are coupled. ATP is never hydrolyzed directly. Instead enzymes shift its high-energy phosphate
groups to other molecules, which are then said to be phosphorylated (fosfor--lated). Phosphorylation primes the molecule to change in a way that
increases its activity, produces motion, or does work. For example, many regulatory enzymes that catalyze key steps in metabolic pathways are activated
by phosphorylation.
Three major stages are involved in the processing of energy-containing nutrients in the body (Figure 24.3):
Stage 1 is digestion in the gastrointestinal tract, described in Chapter 23. The absorbed nutrients are then transported in blood to the tissue cells.
In stage 2, which occurs in the cell cytoplasm, newly delivered nutrients are either built into lipids, proteins, and glycogen by anabolic pathways or
broken down by catabolic pathways to pyruvic acid (pi-roovik) and acetyl CoA (as-til ko-a).
Stage 3, which is almost entirely catabolic, occurs in the mitochondria, requires oxygen, and completes the breakdown of foods, producing carbon
dioxide and water and harvesting large amounts of ATP.

FIGURE 24.3
Three stages
of metabolism
of energy-
containing
nutrients. In
stage 1, foods
are degraded to
absorbable
forms by
digestive
enzymes in the
GI tract.
In stage 2, the
absorbed
nutrients are
transported in
blood to the
body cells,
where they may
be incorporated
into molecules
(anabolism) or
broken down via
glycolysis and
other reactions
to pyruvic acid
and/or acetyl
CoA, and then
funneled into
the pathways of
stage 3.
Stage 3
consists of the
catabolic
pathways of the
Krebs cycle and
oxidative
phosphorylation,
both of which
take place in the
mitochondria.
During the
Krebs cycle,
acetyl CoA is
broken apart: Its
carbon atoms
are liberated as
carbon dioxide
(CO2), and the
hydrogen atoms

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Human Anatomy & Physiology, 7th Edition, Chapter 24 Page 2 of 4

removed are
delivered to a
chain of
receptors (the
electron
transport chain),
which ultimately
delivers them
(as protons and
free electrons)
to molecular
oxygen so that
water is formed.
Some of the
energy released
during the
electron
transport chain
reactions is
used to form
ATP. Stages 2
and 3
collectively
constitute
cellular
respiration.

(Click image to enlarge)

The primary function of cellular respiration, which consists of glycolysis of stage 2 and all events of stage 3, is to generate ATP, which traps some of the
chemical energy of the original food molecules in its own high-energy bonds. Thus, food fuels, such as glycogen and fats, store energy in the body, and
these stores are later mobilized to produce ATP for cellular use.
You do not need to memorize Figure 24.3, but as you will soon see, it provides a cohesive summary of nutrient processing and metabolism in the body.

Oxidation-Reduction Reactions and the Role of Coenzymes

Many of the reactions that take place within cells are oxidation reactions. Oxidation was originally defined as the combination of oxygen with other
elements. Examples are the rusting of iron (the slow formation of iron oxide) and the burning of wood and other fuels. In burning, oxygen combines rapidly
with carbon, producing carbon dioxide, water, and an enormous amount of energy, which is liberated as heat and light. Later it was discovered that
oxidation also occurs when hydrogen atoms are removed from compounds and so the definition was expanded to its current form: Oxidation is the gain of
oxygen or the loss of hydrogen. As explained in Chapter 2, whichever way oxidation occurs, the oxidized substance always loses (or nearly loses)
electrons as they move to (or toward) a substance that more strongly attracts them.
This loss of electrons can be explained by reviewing the consequences of different electron-attracting abilities of atoms. Consider a molecule made up
of a hydrogen atom plus some other kinds of atoms. Because hydrogen is very electropositive, its lone electron usually spends more time orbiting the
other atoms of the molecule. But when a hydrogen atom is removed, its electron goes with it, and the molecule as a whole loses that electron. Conversely,
oxygen is very electron-hungry (electronegative), and so when oxygen binds with other atoms the shared electrons spend more time in oxygens vicinity.
Again, the molecule as a whole loses electrons. As you will soon see, essentially all oxidation of food fuels involves the step-by-step removal of pairs of
hydrogen atoms (and thus pairs of electrons) from the substrate molecules, eventually leaving only carbon dioxide (CO2). Molecular oxygen (O2) is the
final electron acceptor. It combines with the removed hydrogen atoms at the very end of the process, to form water (H2O).
Whenever one substance loses electrons (is oxidized), another substance gains them (is reduced). Thus, oxidation and reduction are coupled reactions
and we speak of oxidation-reduction reactions, or more commonly, redox reactions. The key understanding about redox reactions is that oxidized
substances lose energy and reduced substances gain energy as energy-rich electrons are transferred from the former to the latter. Consequently, as
food fuels are oxidized, their energy is transferred to a bucket brigade of other molecules and ultimately to ADP to form energy-rich ATP.

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Human Anatomy & Physiology, 7th Edition, Chapter 24 Page 3 of 4

Like all other chemical reactions in the body, redox reactions are catalyzed by enzymes. Those that catalyze redox reactions in which hydrogen atoms
are removed are called dehydrogenases (de-hidro-jen-sez), while those catalyzing the transfer of oxygen are oxidases. Most of these enzymes
require the help of a specific coenzyme, typically derived from one of the B vitamins. Although the enzymes catalyze the removal of hydrogen atoms to
oxidize a substance, they cannot accept the hydrogen (hold on or bond to it). Their coenzymes, however, act as hydrogen (or electron) acceptors,
becoming reduced each time a substrate is oxidized. Two very important coenzymes of the oxidative pathways are nicotinamide adenine dinucleotide
(NAD+) (niko-tinah-md), based on niacin, and flavin adenine dinucleotide (FAD), derived from riboflavin. The oxidation of succinic acid to fumaric acid
and the simultaneous reduction of FAD to FADH2, an example of a coupled redox reaction, is

Mechanisms of ATP Synthesis

How do our cells capture some of the energy liberated during cellular respiration to make ATP molecules? There appear to be two mechanisms
substrate-level phosphorylation and oxidative phosphorylation.
Substrate-level phosphorylation occurs when high-energy phosphate groups are transferred directly from phosphorylated substrates (metabolic
intermediates such as glyceraldehyde phosphate) to ADP (Figure 24.4a). Essentially, this process occurs because the high-energy bonds attaching the
phosphate groups to the substrates are even more unstable than those in ATP. ATP is synthesized by this route during one of the steps in glycolysis, and
once during each turn of the Krebs cycle (Figure 24.5). The enzymes catalyzing substrate-level phosphorylations are located in both the cytoplasm and in
the watery matrix inside the mitochondria.

FIGURE 24.4
Mechanisms of
phosphorylation.
(a) Substrate-
level
phosphorylation
occurs when a
high-energy
phosphate group
is transferred
directly from a
substrate to ADP
to form ATP. This
reaction occurs
both in the
cytoplasm and in
the mitochondrial
matrix. (b)
Oxidative
phosphorylation,
which occurs in
mitochondria,
reflects the
activity of electron
transport proteins
that act as proton
pumps to create
(Click image to enlarge) a proton gradient
across the cristae
membranes. The
source of energy
for this pumping
is energy
released during
oxidation of food
molecules. As the
protons flow
passively back
into the
mitochondrial fluid
matrix, the energy
of the
electrochemical
gradient is used

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Human Anatomy & Physiology, 7th Edition, Chapter 24 Page 4 of 4

to bind phosphate
groups to ADP.

FIGURE 24.5
Sites of ATP
formation
during cellular
respiration.
Glycolysis
occurs in the
cytosol. The
Krebs cycle and
the electron
transport chain
reactions occur
in the
mitochondria.
During
glycolysis, each
glucose
molecule is
broken down to
two molecules
of pyruvic acid.
The pyruvic acid
enters the
mitochondrial
matrix, where
the Krebs cycle
decomposes it
to CO2. During
glycolysis and
the Krebs cycle,
small amounts
of ATP are
formed by
substrate-level
phosphorylation.
Chemical
energy from
glycolysis and
(Click image to enlarge) the Krebs cycle,
in the form of
energy-rich
electrons picked
up by
coenzymes, is
then transferred
to the electron
transport chain,
which is built
into the
membrane of
the cristae. The
electron
transport chain
carries out
oxidative
phosphorylation,
which accounts
for most of the
ATP generated
by cellular
respiration.

Oxidative phosphorylation is much more complicated, but it also releases most of the energy that is eventually captured in ATP bonds during cellular
respiration. This process, which is carried out by electron transport proteins forming part of the mitochondria cristae, is an example of a chemiosmotic
process. Chemiosmotic processes couple the movement of substances across membranes to chemical reactions. In this case, some of the energy
released during the oxidation of food fuels (the chemi part of the term) is used to pump (osmo = push) protons (H+) across the cristae membrane into the
intermembrane space (Figure 24.4b). This creates a steep concentration gradient for protons across the membrane. Then, when H+ does flow back across
the membrane (through a membrane channel protein called ATP synthase), some of this gradient energy is captured and used to attach phosphate groups
to ADP.
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