Citric Acid Cycle

Question 1

Citric acid cycle principles

Answer 1

Also known as the TCA cycle or Krebs cycle. Overall purpose is to oxidize acetyl-CoA and produce electron carriers (NADH, FADH2) to feed into the electron transport chain.

Question 2

Citric acid cycle principles

Reactants and products

Answer 2

Note: need to fully memorize this for the MCAT
* Reactants: 1 Acetyl CoA, 3 NAD+, 1 FAD, 2 H2O, 1 GDP + Pi
* Products: 3 NADH, 1 FADH2, 2 CO2, 1 GTP, 3 H+

Question 3

Citric acid cycle principles

Location

Answer 3

Occurs in the mitochondrial matrix in eukaryotes and the cytoplasm in prokaryotes.

Question 4

Citric acid cycle principles

Rate-limiting step

Answer 4

Rate limiting step is isocitrate dehydrogenase, which catalyzes conversion of isocitrate to α-ketoglutarate.
Results in conversion of NAD+ to NADH and production of CO2.

Question 5

Citric acid cycle principles

Checkpoint steps

Answer 5

The three regulatory enzymes (or checkpoints) of the citric acid cycle are:
Citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase complex.
These are irreversible reactions that are allosterically regulated.

Question 6

Citric acid cycle principles

Key steps

Answer 6

Know which enzyme steps result in production of:
* NADH: isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase
* FADH2: succinate dehydrogenase
* GTP: succinyl-CoA synthetase

Question 7

Citric acid cycle steps

Citrate synthase

Answer 7

Convert acetyl-CoA to CoA with coupled conversion of oxaloacetate to citrate.
Enzyme is regulated by negative feedback from downstream products like ATP, NADH, citrate.

Question 8

Citric acid cycle steps

cis-Aconitase

Answer 8

Part of the isomerase class of enzymes.
Converts citrate to isocitrate.

Question 9

Citric acid cycle steps

Isocitrate dehydrogenase

Answer 9

Catalyzes conversion of isocitrate to α-ketoglutarate. The rate-limiting step.
Results in conversion of NAD+ to NADH and production of CO2.
Isocitrate + NAD+ → α-ketoglutarate + CO2 + NADH + H+

Question 10

Citric acid cycle steps

α-ketoglutarate dehydrogenase

Answer 10

Converts α-ketoglutarate to succinyl-CoA, generating CO2 and NADH.
Inhibited by negative feedback from products ATP, NADH, succinyl-CoA.
Activated by ADP and Ca2+.

Question 11

Citric acid cycle steps

Succinyl-CoA synthetase

Answer 11

Converts succinyl-CoA to succinate, generating one GTP.

Question 12

Citric acid cycle steps

Succinate dehydrogenase

Answer 12

Converts succinate to fumarate through oxidation. This produces FADH2.
Succinate dehydrogenase is a flavoprotein, meaning it binds to FAD found in the inner mitochondrial membrane.

Question 13

Citric acid cycle steps

Fumarase

Answer 13

Converts fumarate to malate through a reversible hydration reaction.

Question 14

Citric acid cycle steps

Malate dehydrogenase

Answer 14

Converts malate to oxaloacetate through oxidation, producing NADH.

Question 15

Acetyl CoA production

Answer 15

The pyruvate dehydrogenase complex converts pyruvate to acetyl-CoA prior to entry into the citric acid cycle.

Question 16

Acetyl CoA production

Regulation

Answer 16

Stimulated by insulin and inhibited by acetyl-CoA.
The general principle is to activate this pathway when the body wants to breakdown more glucose into energy.

Question 17

Acetyl CoA production

Enzymatic regulation

Answer 17

Activated through dephosphorylation by pyruvate dehydrogenase phosphatase.
Deactivated through phosphorylation by pyruvate dehydrogenase kinase.

Question 18

Acetyl CoA production

Pyruvate dehydrogenase

Answer 18

Key enzyme of this reaction. Converts pyruvate to acetyl-CoA.
Cofactors are lipoic acid and thiamine.