Citric Acid Cycle Regulation and Related Pathways

14 vocabulary flashcards on key metabolites, enzymes, and regulatory concepts related to the citric acid cycle and its connected pathways.

Glyoxylate Cycle

Variant of the CAC in plants, bacteria, fungi that bypasses decarboxylations to convert two acetyl-CoA into succinate/malate for gluconeogenesis.

Isocitrate Lyase

Glyoxylate-cycle enzyme that splits isocitrate into succinate and glyoxylate, preventing CO₂ loss.

Malate Synthase

Glyoxylate-cycle enzyme that condenses glyoxylate with acetyl-CoA to form malate.

Pyruvate Carboxylase

Mitochondrial enzyme that uses CO₂ and ATP to convert pyruvate to oxaloacetate; allosterically activated by acetyl-CoA.

Acetyl-CoA Carboxylase

Cytosolic enzyme converting acetyl-CoA to malonyl-CoA, committing exported citrate-derived acetyl-CoA to fatty acid synthesis.

ATP production from glucose

glucose → 2 pyruvate = 2 ATP + 2 NADH → 5 ATP (total 7 ATP from glycolysis); 2 pyruvate → 2 Acetyl-CoA = 2 NADH → 5 ATP; 2 Acetyl-CoA → 6 NADH (15 ATP) + 2 FADH2 (3 ATP) + 2 GTP (2 ATP) (total 32 ATP/ glucose, 10 ATP/ CAC turn)

PDH Kinase

adds P group to PDH, inactivating it using ATP

PDH phosphatase

dephosphorylates PDH, activating it

regulators of PDH kinase

activators: ATP, NADH, Acetyl-CoA; inhibitors: ADP, NAD+, Pyruvate

regulators of PDH phosphatase

activators: Ca2+, insulin; inhibitors: ATP, NADH, Acetyl-CoA

irreversible enzymes of CAC

citrate synthase, isocitrate dehydrogenase, a-ketoglutarate dehydrogenase; also malate dehydrogenase is positive and unfavorable, but pulled by the concentration of oxaloacetate

anaplerotic reactions in the CAC

are metabolic pathways that replenish intermediates in the citric acid cycle. Pyruvate dehydrogenase regenerates Acetyl-CoA from pyruvate (from glycolysis). Transaminase generates a-ketoglutarate and alanine from pyruvate; Glutamate regenerates a-Ketoglutarate. Pyruvate carboxylase generates oxaloacetate from pyruvate

glutamate biosynthesis

Via glutamate dehydrogenase: a-Ketoglutarate + NADH + H+ + NH4+ → glutamate + NAD+ + H2O; reversible reductive amination

aspartate biosynthesis

Via transaminase: oxaloacetate + Alanine → Aspartate + Pyruvate (reversible)

excess citrate fate

used for lipid synthesis: citrate → Acetyl-CoA → (via Acetyl-CoA carboxylase + CO2) Malonyl CoA → (via Fatty Acid Synthase + NADPH) Palmitate → further processing in the ER/ mitochondria

glyoxylate cycle

occurs in seeds; triglycerides → FFA → acetyl-CoA → citrate → isocitrate → (via isocitrate lyase) Glyoxylate + Succinate; Acetyl CoA → (via malate synthase) Malate → Oxaloacetate →→→ gluconeogenesis

fate of GC succinate + malate

succinate goes to the mitochondria; malate exported: malate → oxaloacetate → gluconeogenesis