The Citric Acid Cycle

___________________ is the process where cells consume oxygen (O2) and produce carbon dioxide (CO2)

Cellular respiration

Cellular respiration provides energy (ATP) from glucose (more than ___________________)

glycolysis

Cellular respiration occurs in three major stages:

- acetyl CoA production

- acetyl CoA oxidation

- electron transfer and oxidative phosphorylation

Conversion of Pyruvate to Acetyl-CoA

- The pyruvate dehydrogenase complex includes three types of enzymes that collectively remove a ___________________ from pyruvate and produce ___________________

carboxylate group, acetyl-CoA and NADH.

Under aerobic conditions, the pyruvate is transported into the mitochondrial membrane. In the __________________, pyruvate is oxidatively decarboxylated by the ______________________ complex to form acetyl CoA

mitochondrial matrix, pyruvate dehydrogenase

The conversion of pyruvate into acetyl CoA consists of three steps

- Decarboxylation

- Oxidation

- Transfer acetyl group to CoA

the Mechanism of Pyruvate Dehydrogenase reaction is complicated. ______________________ participate

three enzymes and five coenzymes

the 5 Coenzymes in the Mechanism of Pyruvate Dehydrogenase reaction include

- Catalytic cofactors: thiamine pyrophosphate (TPP), lipoic acid, and FAD

- Stoichiometric cofactors: CoA and NAD+

Three enzymes of pyruvate dehydrogenase complex

Pyruvate dehydrogenase (E1)

Dihydrolipoyl transacetylase (E2)

Dihydrolipoyl dehydrogenase (E3)

step 1 of pyruvate dehydrogenase complex

pyruvate dehydrogenase (E1) reaction

- pyruvate undergoes oxidative decarboxylation to form hydroxyethyl-thiamine pyrophosphate (TPP), with CO2 created as a byproduct

step 2 of pyruvate dehydrogenase complex

dihydrolipoyl transacetylase (E2) reaction

- hydroxyethyl breaks away from TPP and transfers to lipoamide to form acetyl-dihydrolipoamide

step 3 of pyruvate dehydrogenase complex

dihydrolipoyl transacetylase (E2) reaction

- acetyl breaks away from dihydrolipoamide and transfers to CoA to form acetyl CoA

step 4 of pyruvate dehydrogenase complex

dihydrolipoyl dehydrogenase (E3) reaction

- dihydrolipoamide is reoxidized by FAD. NAD+ is reduced to NADH, which leads to the regeneration of the oxidized lipoamide

step 1 of citric acid cycle

Catalyzed by citrate synthase

- oxaloacetate and acetyl CoA undergo an aldol condensation to form citryl CoA, followed by a hydrolysis reaction to form citrate

step 2 of citric acid cycle

Catalyzed by aconitase

- citrate undergoes dehydration to form cis-aconitate, followed by hydration to form isocitrate

step 3 of citric acid cycle

Catalyzed by isocitrate dehydrogenase

- an oxidative decarboxylation reaction with isocitrate and NAD+ as reactants and alpha-ketoglutarate, NADH, and CO2 as products

step 4 of citric acid cycle

Catalyzed by alpha-ketoglutarate dehydrogenase

- a second oxidative decarboxylation reaction with alpha-ketoglutarate and NAD+ as reactants and succinyl CoA, NADH, and CO2 as products

step 5 of citric acid cycle

Catalyzed by succinyl CoA synthetase (succinate thiokinase)

- example of substrate-level phosphorylation

- thioester bond of succinyl CoA gets cleaved

- succinyl CoA, ADP, and Pi are reactants and succinate, CoA, and ATP as products

steps 6-8 of citric acid cycle

Step 6: Succinate is oxidized to fumarate, producing FADH2, catalyzed by succinate dehydrogenase.

Step 7: Fumarate is hydrated to malate, catalyzed by fumarase.

Step 8: Malate is oxidized to regenerate oxaloacetate, producing NADH, catalyzed by malate dehydrogenase

1 NADH = 2.5 ATP

1 FADH2 = 1.5 ATP

Each round of the citric acid cycle generates

three NADH, one FADH2, and one GTP or ATP.

Flux through the citric acid cycle is regulated primarily by ______________ at three steps.

feedback inhibition

the pyruvate dehydrogenase complex is regulated ______________ and by

allosterically, reversible phosphorylation

The formation of acetyl CoA from pyruvate is _________________ in animal cells.

irreversible

Acetyl CoA has two principle fates:

- metabolism by the citric acid cycle

- incorporation into fatty acids.

The key control points in the citric acid cycle are the reactions catalyzed by

isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase

_________________ Functions of the Citric Acid Cycle

- The citric acid cycle supplies _________________ for the synthesis of other compounds, and, citric acid cycle intermediates can be replenished.

Amphibolic, precursors

__________________ Reactions: Citric acid cycle intermediates are precursors of other molecules.

Cataplerotic

An example of amino acid formation from a citric acid cycle intermediate. Glutamate is a precursor of the amino acids __________________

glutamine, arginine, and proline.

________________ reactions replenish citric acid cycle intermediates. Intermediates that are diverted to other pathways can be replenished.

Anaplerotic

In the pyruvate dehydrogenase complex, covalent modification of E1, ______________________ leads to inactivation

phosphorylation