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Ketoglutarate [SC] CoASH

dehydrogenase FADH —N

Succinate [4C]

CoASH

CoASH

GTP GDP+P

Succinyl CoA synthetase

Ketoglutarate dehydrogenase

Ketoglutarate dehydrogenase

GTP GDP+P

Succinyl CoA synthetase

Figure 4 The oxidative decarboxylation of pyruvate and the tricarboxylic acid cycle.

evidenced by the increased cellular pyruvate and cardiac and skeletal muscle weakness in beriberi caused by thiamine deficiency. Pyruvate dehydrogenase catalyzes a central reaction in carbohydrate metabolism, and therefore its activity is regulated by both allosteric and covalent mechanisms.

Acetyl-CoA can be produced from pyruvate but also from fatty acids released from fat stores and from amino acids released from proteolysis of protein tissue, which can be converted to acetyl-CoA or cycle intermediates. In the first of the eight enzymatic reactions, acetyl-CoA (2C) combines with oxaloacetate (4C), forming citrate (6C) and releasing the CoA for further reactions with pyruvate to acetyl-CoA. A cycle of reactions follows in which two molecules of CO2 are released and three molecules of NADH + H+ and one of FADH2 are produced along with one molecule of GTP (equivalent to ATP). At the end of the cycle, oxaloacetate is regenerated and able to react again with another molecule of acetyl-CoA, and so the cycle continues (Figure 4).

In the electron transfer chain, each NADH + H+ yields approximately 3 ATP and FADH2 yields 2

ATP. Thus, each rotation of the TCA cycle produces approximately 12 ATP (3 NADH + H+« 9 ATP + 1 FADH2 « 2 ATP + 1 GTP). Because two molecules of acetyl-CoA are formed from one glucose molecule, the TCA cycle rotates twice for each molecule of glucose respired, producing a net of 24 ATP (Table 1).

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