Cellular Metabolism Physiology

CELLULAR METABOLISM
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Metabolism (1 of 3)
Metabolism: The sum of all chemical reactions involved

in maintaining the dynamic state of a cell or organism.
• Pathway: A series of biochemical reactions.
• Catabolism: The process of breaking down large nutrient
molecules into smaller molecules with the concurrent
production of energy.
• Anabolism: The process of synthesizing larger molecules
from smaller ones.
Metabolism (2 of 3)
Metabolism is the sum of catabolism and anabolism.
A Mitochondrion
• Figure 26.3(a) Schematic of a mitochondrion cut to reveal the

internal organization.
The Common Metabolic Pathway
• The two parts to the common catabolic pathway:
• The citric acid cycle, also called the tricarboxylic acid cycle (TCA) or Krebs cycle.
• Electron transport chain and phosphorylation, together called oxidative
phosphorylation.
• Four principal compounds participating in the common catabolic pathway are:
• AMP, ADP, and ATP: agents for the storage and transfer of phosphate groups.
• NAD+/NADH: agents for the transfer of electrons in biological oxidation-reduction
reactions.
• FAD/FADH2: agents for the transfer of electrons in biological oxidation-reduction
reactions.
• Coenzyme A; abbreviated CoA or CoA-SH: An agent for the transfer of acetyl
groups.
Adenosine Triphosphate (ATP) (1 of 2)
ATP is the most important compound involved in the

transfer of phosphate groups.
• ATP contains two phosphoric anhydride bonds and one
phosphoric ester bond.
Adenosine Triphosphate (ATP) (2 of 2)
• Hydrolysis of the terminal phosphate (anhydride) of ATP gives ADP, dihydrogen

phosphate ion, and energy.
• Hydrolysis of a phosphoric anhydride liberates more energy than the hydrolysis of a

phosphoric ester.
• We say that ATP and ADP each contain high-energy phosphoric anhydride bonds.
• ATP is a universal carrier of phosphate groups.
• ATP is also a common currency for the storage and transfer of energy.
NAD+/NADH (1 of 2)
• Nicotinamide adenine dinucleotide (NAD+) is a biological

oxidizing agent.
NAD+/NADH (2 of 2)
• NAD+ is a two-electron oxidizing agent, and is reduced to NADH.

• NADH is a two-electron reducing agent, and is oxidized to NAD+. The
structures shown here are the nicotinamide portions of NAD+ and NADH.
• NADH is an electron and hydrogen ion transporting molecule.
FAD/FADH2 (1 of 2)
• Flavin adenine dinucleotide (FAD) is also a biological

oxidizing agent.
accessible website, in whole or in part. 1
FAD/FADH2 (2 of 2)
• FAD is a two-electron oxidizing agent, and is reduced to FADH 2.

• FADH2 is a two-electron reducing agent, and is oxidized to FAD.
• Only the flavin moiety is shown in the structures below.
Coenzyme A (1 of 2)
• Coenzyme A (CoA) is an acetyl group carrier.

• Like NAD+ and FAD, coenzyme A contains a unit of ADP.
• CoA is often written CoA-SH to emphasize the fact that it contains a
sulfhydryl group.
• The vitamin part of coenzyme A is pantothenic acid.
• The acetyl group of acetyl CoA is bound as a high-energy thioester.
Coenzyme A (2 of 2)
• Figure 26.7 The structure of coenzyme A The business end is

the -SH (sulfhydryl) group at the left end.
What Is Glycolysis?
Glycolysis is a set of anaerobic reactions, ones that does not need
oxygen to be performed
It takes glucose and breaks it down into pyruvate
This has the result of creating two ATP, which can release energy
Overall, this process creates four ATP, but it uses two ATP early in
the reaction. This means that there is a net gain of two ATP.
The overall equation for this pathway is:
1 glucose + 2 ATP ⟶ 2 pyruvate + 2 NADH + 4 ATP + 2 H2O
1
Source: https://www.expii.com/t/glycolysis-cellular-respiration-summary-steps-10136 1
accessible
Source: website, in whole or in part.
https://www.news-medical.net/health/Glycolysis-Metabolic-Pathway.aspx 1
1
Source: https://www.sciencefacts.net/wp-content/uploads/2021/09/Anaerobic-Respiration-Diagram.jpg 2
Source: https://www.macmillanhighered.com/BrainHoney/Resource/6716/digital_first_content/trunk/
test/hillis2e/hillis2e_ch06_4.html
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Source: https://open.oregonstate.education/app/uploads/sites/85/2019/10/animal-nutrition-28.jpg
Citric Acid Cycle (1 of 9)
• A simplified view of the citric acid. The fuel is the two-carbon acetyl
group of acetyl CoA. With each turn of the cycle two carbons are
released as CO2.
Step 1: The condensation of acetyl CoA with oxaloacetate:

• The high-energy thioester of acetyl CoA is hydrolyzed.
• This hydrolysis provides the energy to drive Step 1.
• Citrate synthase, an allosteric enzyme, is inhibited by NADH, ATP, and

succinyl-CoA.
Step 2: Dehydration and rehydration, catalyzed by aconitase, gives

isocitrate.
• Citrate and aconitate are achiral; neither has a stereocenter.

• Isocitrate is chiral; it has 2 stereocenters and 4 stereoisomers are possible.
• Only one of the 4 possible stereoisomers is formed in the cycle.
Step 3: Oxidation of isocitrate to oxalosuccinate followed by decarboxylation

gives a-ketoglutarate.
• Isocitrate dehydrogenase is an allosteric enzyme; it is inhibited by ATP and NADH, and

activated by ADP and NAD+.
Step 4: Oxidative decarboxylation of -ketoglutarate to succinyl-

CoA.
• The two carbons of the acetyl group of acetyl CoA are still present in
succinyl CoA.
• This multienzyme complex is inhibited by ATP, NADH, and succinyl CoA.
It is activated by ADP and NAD+.
• Step 5: Formation of succinate.
• The two CH2-COO– groups of succinate are now equivalent.

• A molecule of GTP is produced. Like ATP, GTP stores energy in the
form of high-energy phosphoric anhydride bonds.
• Step 6: Oxidation of succinate to fumarate.
• Step 7: Hydration of fumarate to L-malate.
• Malate is chiral and can exist as a pair of enantiomers; It is

produced in the cycle as a single stereoisomer.
• Step 8: Oxidation of malate
• Oxaloacetate now can react with acetyl CoA to start another round of
the cycle by repeating Step 1.
• The overall reaction of the cycle is:
Control of the cycle:

• Controlled by three feedback mechanisms.
• Citrate synthase: inhibited by ATP, and NADH; also product
inhibition by citrate.
• Isocitrate dehydrogenase: activated by ADP and NAD+,
inhibited by ATP and NADH.
• -Ketoglutarate dehydrogenase complex: inhibited by ATP
and NADH; activated by ADP and NAD+.
TCA Cycle in Catabolism
The catabolism of proteins, carbohydrates, and fatty acids all

feed into the citric acid cycle at one or more points:
Oxidative Phosphorylation (1 of 2)
Carried out by four closely related multisubunit membrane-bound

complexes and two electron carriers, coenzyme Q and
cytochrome c.
• In a series of oxidation-reduction reactions, electrons from FADH2 and
NADH are transferred from one complex to the next until they reach O2.
• O2 is reduced to H2O.
• As a result of electron transport, protons are pumped across the inner

membrane to the intermembrane space.
Oxidative Phosphorylation (2 of 2)
• Figure 26.10 Schematic diagram of the electron and H+ transport chain

and subsequent phosphorylation.
Complex I
The sequence starts with Complex I:

• This large complex contains some 40 subunits, among them are a
flavoprotein, several iron-sulfur (FeS) clusters, and coenzyme Q
(CoQ, ubiquinone).
• Complex I oxidizes NADH to NAD+.
• The oxidizing agent is CoQ, which is reduced to CoQH2.
• Some of the energy released in the oxidation of NADH is used to

move 2H+ from the matrix into the intermembrane space.
Complex II
• Complex II oxidizes FADH2 to FAD.

• The oxidizing agent is CoQ, which is reduced to CoQH 2.
• The energy released in this reaction is not sufficient to pump

protons across the membrane.
Complex III
• Complex III delivers electrons from CoQH2 to cytochrome c (Cyt c).
• This integral membrane complex contains 11 subunits, including

cytochrome b, cytochrome c1, and FeS clusters.
• Complex III has two channels through which the two H+ from each CoQH2
oxidized are pumped from the matrix into the intermembrane space.
Complex IV
• Complex IV is also known as cytochrome oxidase.

• It contains 13 subunits, one of which is cytochrome a3
• Electrons flow from Cyt c (oxidized) in Complex III to Cyt a3 in Complex IV.
• From Cyt a3 electrons are transferred to O2.
• During this redox reaction, H+ are pumped from the matrix into the
intermembrane space.
Summing the reactions of Complexes I - IV, six H+ are pumped
out per NADH and four H+ per FADH2.
Chemiosmotic Pump (1 of 3)
To explain how electron and H+ transport produce the chemical energy of

ATP, Peter Mitchell proposed the chemiosmotic theory that electron
transport is accompanied by an accumulation of protons in the
intermembrane space of the mitochondrion, which in turn creates osmotic
pressure; the protons driven back to the mitochondrion under this pressure
generate ATP.
• The energy-releasing oxidations give rise to proton pumping and a pH
gradient is created across the inner mitochondrial membrane.
• There is a higher concentration of H+ in the intermembrane space than
inside the mitochondria.
• This proton gradient provides the driving force to propel protons back into
the mitochondrion through the enzyme complex called proton-
translocating ATPase.
• Protons flow back into the matrix through channels in the F0 unit of ATP
synthase.
• The flow of protons is accompanied by formation of ATP in the F1 unit of
ATP synthase.
The functions of oxygen are:

• To oxidize NADH to NAD+ and FADH2 to FAD so that these molecules can
return to participate in the citric acid cycle.
• Provide energy for the conversion of ADP to ATP.
• The overall reactions of oxidative phosphorylation are:
• Oxidation of each NADH gives 3 ATP.

• Oxidation of each FADH2 gives 2 ATP.

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Cellular Metabolism Physiology

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CELLULAR METABOLISM

Metabolism: The sum of all chemical reactions involved

Metabolism is the sum of catabolism and anabolism.

• Figure 26.3(a) Schematic of a mitochondrion cut to reveal the

ATP is the most important compound involved in the

• Hydrolysis of the terminal phosphate (anhydride) of ATP gives ADP, dihydrogen

• Hydrolysis of a phosphoric anhydride liberates more energy than the hydrolysis of a

• Nicotinamide adenine dinucleotide (NAD+) is a biological

• NAD+ is a two-electron oxidizing agent, and is reduced to NADH.

• NADH is an electron and hydrogen ion transporting molecule.

• Flavin adenine dinucleotide (FAD) is also a biological

• FAD is a two-electron oxidizing agent, and is reduced to FADH 2.

• Coenzyme A (CoA) is an acetyl group carrier.

• Figure 26.7 The structure of coenzyme A The business end is

The overall equation for this pathway is:

1 glucose + 2 ATP ⟶ 2 pyruvate + 2 NADH + 4 ATP + 2 H2O

Step 1: The condensation of acetyl CoA with oxaloacetate:

• Citrate synthase, an allosteric enzyme, is inhibited by NADH, ATP, and

Step 2: Dehydration and rehydration, catalyzed by aconitase, gives

• Citrate and aconitate are achiral; neither has a stereocenter.

Step 3: Oxidation of isocitrate to oxalosuccinate followed by decarboxylation

• Isocitrate dehydrogenase is an allosteric enzyme; it is inhibited by ATP and NADH, and

Step 4: Oxidative decarboxylation of -ketoglutarate to succinyl-

• Step 5: Formation of succinate.

• The two CH2-COO– groups of succinate are now equivalent.

• Step 6: Oxidation of succinate to fumarate.

• Step 7: Hydration of fumarate to L-malate.

• Malate is chiral and can exist as a pair of enantiomers; It is

• Step 8: Oxidation of malate

Control of the cycle:

The catabolism of proteins, carbohydrates, and fatty acids all

Carried out by four closely related multisubunit membrane-bound

• As a result of electron transport, protons are pumped across the inner

• Figure 26.10 Schematic diagram of the electron and H+ transport chain

The sequence starts with Complex I:

• Some of the energy released in the oxidation of NADH is used to

• Complex II oxidizes FADH2 to FAD.

• The energy released in this reaction is not sufficient to pump

• Complex III delivers electrons from CoQH2 to cytochrome c (Cyt c).

• This integral membrane complex contains 11 subunits, including

• Complex IV is also known as cytochrome oxidase.

To explain how electron and H+ transport produce the chemical energy of

The functions of oxygen are:

• The overall reactions of oxidative phosphorylation are:

• Oxidation of each NADH gives 3 ATP.

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