Krebs/citric acid/tricarboxylic acid cycle
The Krebs cycle, AKA the citric acid cycle (CAC) or tricarboxylic acid (TCA) cycle,
is a fundamental metabolic pathway that plays a key role in cellular respiration.
This cycle is a series of enzyme-catalysed chemical reactions that generate
energy through the oxidation of acetyl-CoA derived from carbohydrates, fats and
proteins.
It occurs in the mitochondrial matrix of eukaryotic cells and in the cytoplasm of
prokaryotes and it serves multiple purposes:
1. Energy production: the primary function is to produce high energy
electron carriers (NADH and FADH2) that feed into the electron transport
chain to generate ATP.
2. Biosynthetic role: intermediates of the cycle serve as precursors for the
biosynthesis of various biomolecules.
3. Metabolic integration: it integrates and interconnects with other
metabolic pathways, such as gluconeogenesis and amino acid metabolism
Acetyl-CoA+3NAD+FAD+GDP+Pi+2H202CO2+3NADH+FADH2+GTP+COA+3H
Steps of the Krebs cycle
Net yield per Acetyl-
CoA
1. Formation of citrate (enzyme: citrate synthase)
Reaction: Acetyl-CoA + Oxaloacetate + H2O → Citrate + CoA-SH
Acetyl-CoA (2 carbons) combines with oxaloacetate (4 carbons) to form citrate (6
carbons).
2. Conversion of citrate to isocitrate (enzyme: aconitase)
Reaction: Citrate ⇌ cis-Aconitate ⇌ Isocitrate
Citrate is converted to isocitrate via cis-aconitate as an intermediate.
3. Oxidation of Isocitrate to α-Ketoglutarate (Enzyme: Isocitrate dehydrogenase)
Reaction: Isocitrate + NAD+ → α-Ketoglutarate + NADH + H+ + CO2
Isocitrate is oxidized and decarboxylated to α-ketoglutarate, producing NADH
and releasing CO2.
4. Conversion of α-Ketoglutarate to Succinyl-CoA (Enzyme: α-Ketoglutarate
dehydrogenase complex)
Reaction: α-Ketoglutarate + NAD+ + CoA-SH → Succinyl-CoA + NADH +
H+ + CO2
α-Ketoglutarate undergoes oxidative decarboxylation to form succinyl-CoA,
producing NADH and releasing CO2.
5. Conversion of succinyl -CoA to Succinate (Enzyme: Succinyl-CoA synthetase)
Reaction: Succinyl-CoA + GDP + Pi → Succinate + CoA-SH + GTP
Succinyl-CoA is converted to succinate, generating GTP (or ATP in some
organisms) through substrate-level phosphorylation.
6. Oxidation of Succinate to Fumarate (Enzyme: Succinate dehydrogenase)
Reaction: Succinate + FAD → Fumarate + FAD
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