TCA Cycle

Question 1

Leigh Disease

Answer 1

Characterized by muscle weakness, difficulty breathing, commonly caused by deficiencies in pyruvate dehydrogenase complex (PDC).
Results in buildup of lactate (causing lactic acidosis) and a deficit in mitochondrial energy production.

Question 2

Control points of TCA cycle:

Answer 2

Citrate synthase
Isocitrate dehydrogenase
alpha-ketogultarate dehydrogenase
Malate dehydrogenase

Question 3

Citrate synthase in TCA

Answer 3

inhibited by product (citrate) and activated by substrate (oxaloacetate)

Question 4

Isocitrate dehydrogenase in TCA

Answer 4

Major rate-limiting step
Allosteric regulation - ADP enhances enzyme affinity for substrate; ATP and NADH inhibit the enzyme
When energy status is high, citrate accumulates and halts glycolysis and shunts acetyl CoA towards fatty acid synthesis

Question 5

Alpha-ketoglutarate in TCA

Answer 5

Rate-limiting step
Inhibited by high levels of NADH, succinyl CoA, and ATP
When energy status is high, alpha-ketoglutarate accumulates and is used in generating amino acids and nucleotide bases

Question 6

Malate dehydrogenase

Answer 6

Inhibited by high NADH

Question 7

FADH2 in ETC

Answer 7

Electrons from succinate enter Complex II (succinate dehydrogenase) but it does not pump protons itself, instead it donates electrons to CoQ and then Complex III.