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AAT Bioquest

What are the steps of Krebs cycle?

Posted March 30, 2023


Answer

Krebs cycle takes place over 8 distinct steps, with a different enzyme catalyzing each step. 

Step 1: Acetyl CoA condenses with 4-carbon compound Oxaloacetate (4C), forming citrate (6C). Coenzyme A is released. The reaction is catalyzed by citrate synthase.

Step 2: The enzyme aconitase converts citrate to its more unstable isomer, isocitrate. 

Step 3: Isocitrate undergoes dehydrogenation and decarboxylation, forming 5C 𝝰-ketoglutarate. A molecular form of CO2 is released. The reaction is catalyzed by Isocitrate dehydrogenase, an NAD+ dependent enzyme. In this step, NAD+ is converted to NADH.

Step 4: α-ketoglutarate, a 5C compound, undergoes oxidative decarboxylation to form succinyl CoA, a 4C compound. The reaction is catalyzed by the α-ketoglutarate dehydrogenase enzyme complex. In this step, one CO2 molecule is released and NAD+ is converted to NADH.

Step 5: The enzyme succinyl CoA synthetase converts succinyl CoA to succinate (C4H4O4-2). This is accompanied by substrate-level phosphorylation of GDP (Guanosine diphosphate) to obtain GTP (Guanosine-5'-triphosphate).

Step 6: The enzyme succinate dehydrogenase oxidizes succinate to fumarate (C4H4O4). In the process, FAD is converted to FADH2.

Step 7: The enzyme fumarase adds one H2O molecule to fumarate, converting it to malate (C4H6O5). 

Step 8: Malate is dehydrogenated to form oxaloacetate (C4H4O5), which combines with another acetyl CoA molecule, starting the new cycle. The hydrogens that are removed get transferred to NAD+ forming NADH. This reaction is catalyzed by the enzyme malate dehydrogenase.

Additional resources

Modelling the Krebs cycle and oxidative phosphorylation

Cellular Processes

Amplite® Colorimetric Pyruvate Assay Kit