Bio 2 Chapter 16

Chapter 16 The Citric Acid Cycle
 The pyruvate produced by glycolysis is oxidized to H2O and CO2.

 This aerobic phase of catabolism is called respiration.
 Catabolism of proteins, fats and carbohydrates occurs in the three stages of
cellular respiration (Fig. 16-1).
 Stage 1 : Oxidation of fatty acids, glucose and some amino acids yields
acetly-CoA.
 Stage 2 : Oxidation of acetyl groups in the citric acid cycle yields CO 2 and
energy.
- The energy released is conserved in the reduced electron carriers
NADH and FADH2.
 Stage 3 : The electrons are transferred to O 2 (the final electron acceptor) via
a chain of electron-carrying molecules known as the respiratory chain.
- In the course of electron transfer, the energy is conserved in the form
of ATP by a process called oxidative phosphorylation.
 Citric acid cycle is also called the tricarboxylic acid (TCA) cycle or the
Krebs cycle.
16.1 Production of Acetyl-CoA (Activated Acetate)
 Pyruvate is oxidized to acetly-CoA and CO2 by the pyruvate

dehydrogenase (PDH) complex in the mitochondria of eukaryotic cells.
 The overall reaction is an oxidative decarboxylation (Fig. 16-2).
 Pyruvate dehydrogenase complex requires five coenzymes.
- FAD
- NAD+
- CoA : Coenzyme A (an acyl carrier) (Fig. 16-3).
- TPP : Thiamine pyrophosphate
- Lipoate
 Pyruvate dehydrogenase complex consists of three distinct enzymes.

- E1 : Pyruvate dehydrogenase
- E2 : Dihydrolipoyl transacetylase
- E3 : Dihydrolipoyl dehydrogenase
 PDH complex carries out the five consecutive reactions in the
decarboxylation and dehydrogenation of pyruvate (Fig. 16-6).
 E1 catalyzes first the decarboxylation of pyruvate, producing hydroxyethyl-
TPP, and then the oxidation of the hydroxyethyl group to an acetyl group.
The electrons from this oxidation reduce the disulfide of lipoate bound to E 2,
and the acetyl group is transferred into thioester linkage with one —SH
group of reduced lipoate.
 E2 catalyzes the transfer of the acetyl group to coenzyme A, forming acetyl-
CoA.
 E3 catalyzes the regeneration of the disulfide (oxidized) form of lipoate;
electrons pass first to FAD, then to NAD+.
16.2 Reactions of the Citric Acid Cycle
 Oxidation of acetyl- CoA is carried out by the citric acid cycle (eight steps)
(Fig. 16-7).
 In each turn of the cycle, one acetyl group (two carbons) enters as acetyl-
CoA and two molecules of CO2 leave; one molecule of oxaloacetate is used
to form citrate and one molecule of oxaloacetate is regenerated.
 The energy of this oxidation is conserved in the reduced coenzymes NADH
and FADH2.
 Reactions occur in the mitochondria of eukaryotic cells.
 -ketoglutarate dehydrogenase complex (E1+E2+E3) is similar to pyruvate
dehydrogenase complex in both structure and function.
 A substrate-level phosphorylation occurs.
 The GTP formed by succinyl- CoA synthetase can donate its terminal
phosphoryl group to ADP to form ATP, in a reversible reaction catalyzed by
nucleoside diphosphate kinase.
GTP + ADP GDP + ATP

The Energy of Oxidations in the Cycle Is Efficiently Conserved
 The energy released by these oxidations was conserved in the reduction of 3
NAD+ and 1 FAD and the production of 1 ATP or GTP.
 At the end of the cycle a molecule of oxaloacetate was regenerated.
 Products of one turn of the citric acid cycle (Fig. 16-14).
 3 NADH, 1 FADH2, 1 GTP (or ATP) and 2 CO2 are released in the oxidative
decarboxylation reactions of 1 acetyl-CoA.
 Stoichiometry of NADH, FADH2 and ATP formation in the aerobic oxidation
of 1 glucose
NADH FADH2 ATP (or GTP) CO2
Glycolysis 2 2
PDH Reaction 2 2
Citric Acid Cycle 6 2 2 4
 In oxidative phosphorylation,
- passage of two electrons from NADH to O2 yields about 2.5 ATP
- passage of two electrons from FADH2 to O2 yields about 1.5 ATP
 After oxidative phosphorylation, 32 ATP are obtained per glucose.
Citric Acid Cycle Components Are Important Biosynthetic Intermediates

 Besides its role in the oxidative catabolism of carbohydrates, fatty acids, and
amino acids, the cycle provides precursors for many biosynthetic pathways
in anabolism (Fig. 16-16).
16.3 Regulation of the Citric Acid Cycle
 Pyruvate dehydrogenase complex of mammals

- is inhibited by ATP, acetyl-CoA, NADH and fatty acids
- is activated by AMP, CoA, NAD+ and Ca2+ (Fig. 16-19).
 The citric acid cycle is regulated at its three exergonic steps catalyzed by
citrate synthase, isocitrate dehydrogenase and -ketoglutarate
dehydrogenase complex.
 Citrate synthase
- is inhibited by NADH, succinyl-CoA, citrate and ATP
- is activated by ADP (Fig. 16-19).
 Isocitrate dehydrogenase
- is inhibited by ATP
- is activated by Ca2+ and ADP (Fig. 16-19).
 -ketoglutarate dehydrogenase complex
- is inhibited by succinyl-CoA and NADH
- is activated by Ca2+ (Fig. 16-19).
16.4 The Glyoxylate Cycle
 Conversion of phosphoenolpyruvate to pyruvate and of pyruvate to acetyl-

CoA are irreversible.
 Phosphoenolpyruvate can be synthesized from oxaloacetate in
gluconeogenesis.
 A cell or organism is unable to convert fuels or metabolites that are degraded
to acetate (fatty acids and certain amino acids) into carbohydrates.
 In many organisms other than vertebrates, the glyoxylate cycle serves as a

mechanism for converting acetate to carbohydrate.
 In plants, the pathway takes place in glyoxysomes (specialized
peroxisomes).
 The glyoxylate cycle produces four-carbon compounds from acetate (Fig. 16-
20).
 Enzymes of the glyoxylate cycle catalyze the net conversion of acetate to
succinate or other four-carbon intermediates of the citric acid cycle .
 Acetyl-CoA condenses with oxaloacetate to form citrate, and citrate is
converted to isocitrate, exactly as in the citric acid cycle.
 The next step is not the breakdown of isocitrate by isocitrate dehydrogenase
but the cleavage of isocitrate by isocitrate lyase, forming succinate and
glyoxylate.
 The glyoxylate condenses with a second molecule of acetyl-CoA to yield
malate by malate synthase.
 The malate is oxidized to oxaloacetate.
 Each turn of the glyoxylate cycle consumes two molecules of acetyl-CoA
and produces one molecule succinate, available for biosynthetic purposes.
2 Acetyl-CoA + NAD+ succinate + 2 CoA + NADH + H+
 There is a relationship between the glyoxylate and citric acid cycle (Fig. 16-
24).
- Succinate may be converted through fumarate and malate into
oxaloacetate.
- Oxaloacetate is converted to phosphoenolpyruvate and thus to glucose
by gluconeogenesis.
 Vertebrates do not have the enzymes specific to the glyoxylate cycle.
- They cannot bring about the net synthesis of glucose from (acetyl-
CoA) lipids.
 Germinating seeds can convert the carbon of stored lipids into glucose.
FIGURE 16-24 Relationship between the glyoxylate and citric acid cycles.

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Chapter 16 The Citric Acid Cycle

 The pyruvate produced by glycolysis is oxidized to H2O and CO2.

16.1 Production of Acetyl-CoA (Activated Acetate)

 Pyruvate is oxidized to acetly-CoA and CO2 by the pyruvate

 Pyruvate dehydrogenase complex consists of three distinct enzymes.

16.2 Reactions of the Citric Acid Cycle

GTP + ADP GDP + ATP

NADH FADH2 ATP (or GTP) CO2

Citric Acid Cycle Components Are Important Biosynthetic Intermediates

 Pyruvate dehydrogenase complex of mammals

 Conversion of phosphoenolpyruvate to pyruvate and of pyruvate to acetyl-

 In many organisms other than vertebrates, the glyoxylate cycle serves as a

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