Biology · Ch 13 — Respiration and Energy Transfer
Krebs Cycle (TCA Cycle / Citric Acid Cycle)
Krebs Cycle (TCA Cycle / Citric Acid Cycle)
Pyruvic acid's 2-carbon acetyl fragment (as acetyl-CoA) is completely oxidised in the mitochondrial matrix through the Krebs cycle - also called the TCA (tricarboxylic acid) cycle or citric acid cycle. This cycle serves as the common oxidative pathway for carbohydrates, fats and proteins alike, and several of its intermediates also double as starting material for synthesising biomolecules such as glutamate and aspartate.
Acetyl-CoA (2C) condenses with oxaloacetic acid (4C), catalysed by citrate synthase, to form citric acid (6C), releasing free CoA-SH in the process. Citric acid is then oxidised step by step by a series of mitochondrial enzymes, releasing CO₂ at two points along the way, and this sequence of oxidations finally regenerates oxaloacetic acid, completing the cycle. There are four oxidation steps in the cycle in all, each catalysed by a dehydrogenase (an oxidoreductase) using either NAD⁺ or FAD⁺ as its coenzyme; these coenzymes are correspondingly reduced to NADH+H⁺ and FADH₂, which go on to transfer their electrons to the mitochondrial electron transport chain to be re-oxidised. One molecule of GTP (equivalent to ATP) is also generated, by substrate-level phosphorylation, for every molecule of citric acid oxidised.
The full sequence of the cycle, as shown in Fig. 13.1, runs:
- Acetyl-CoA (2C) + Oxaloacetate (4C) → Citrate (6C) - enzyme: citrate synthase; a condensation reaction; releases CoA-SH.
- Citrate (6C) → cis-Aconitate (6C) - enzyme: aconitase; a dehydration reaction (loss of H₂O).
- cis-Aconitate (6C) → Isocitrate (6C) - enzyme: aconitase; a hydration reaction (addition of H₂O).
- Isocitrate (6C) → Oxalosuccinic acid (6C) → alpha-Ketoglutarate (5C) - enzyme: isocitrate dehydrogenase; oxidative decarboxylation; releases CO₂ and reduces NAD⁺ to NADH+H⁺.
- alpha-Ketoglutarate (5C) → Succinyl-CoA (4C) - enzyme: alpha-ketoglutarate dehydrogenase complex; oxidative decarboxylation; releases CO₂, consumes CoA-SH, and reduces NAD⁺ to NADH+H⁺.
- Succinyl-CoA (4C) → Succinate (4C) - enzyme: succinyl-CoA synthetase; substrate-level phosphorylation (GDP(ADP) + Pᵢ → GTP(ATP)); releases CoA-SH.
- Succinate (4C) → Fumarate (4C) - enzyme: succinate dehydrogenase; a dehydrogenation (oxidation); reduces FAD to FADH₂.
- Fumarate (4C) → Malate (4C) - enzyme: fumarase; a hydration reaction (addition of H₂O).
- Malate (4C) → Oxaloacetate (4C) - enzyme: malate dehydrogenase; a dehydrogenation (oxidation); reduces NAD⁺ to NADH+H⁺, regenerating the oxaloacetate the cycle started with.
Per turn of the cycle (that is, per acetyl-CoA, or per pyruvate molecule originally entering it), the net yield is 2 CO₂, 3 NADH+H⁺, 1 FADH₂, and 1 GTP(ATP) by substrate-level phosphorylation. Since each glucose molecule yields two pyruvate molecules, the Krebs cycle turns twice for every glucose molecule fully respired. …
What this figure shows. A circular pathway diagram beginning and ending at Oxaloacetate (4C). Acetyl-CoA (2C) condenses with oxaloacetate, via citrate synthase (a condensation reaction releasing CoA-SH), to give Citrate (6C); aconitase dehydrates this to cis-Aconitate (6C), then rehydrates it to Isocitrate (6C); isocitrate dehydrogenase oxidatively decarboxylates it, releasing CO2 and forming NADH+H+, through Oxalosuccinic acid (6C) to alpha-Ketoglutarate (5C); the alpha-ketoglutarate dehydrogenase complex oxidatively decarboxylates this, releasing CO2 and forming NADH+H+ while consuming CoA-SH, to give Succinyl-CoA (4C); succinyl-CoA synthetase converts this to Succinate (4C) through substrate-level phosphorylation (GDP(ADP)+Pi to GTP(ATP)), releasing CoA-SH; succinate dehydrogenase oxidises Succinate to Fumarate (4C), producing FADH2; fumarase hydrates Fumarate to Malate (4C); and malate dehydrogenase oxidises Malate back to Oxaloacetate (4C), producing NADH+H+ and …