The citric acid cycle as pathway for metabolic interconversion

In addition to its role in oxidation of acetyl CoA, the citric acid cycle is an important central metabolic pathway, providing the link between carbohydrate, fat and amino

Citric Cycle Metabolism
Figure 5.19 The GABA shunt — an alternative to a-ketoglutarate dehydrogenase in the citric acid cycle.

acid metabolism. Many of the intermediates can be used for the synthesis of other compounds:

a-Ketoglutarate and oxaloacetate can give rise to the amino acids glutamate and aspartate respectively (section 9.3.1.2).

Oxaloacetate is the precursor for glucose synthesis in the fasting state (section 5.7).

Citrate is used as the source of acetyl CoA for fatty acid synthesis in the cytosol in the fed state (section 5.6.1).

If oxaloacetate is removed from the cycle for glucose synthesis, it must be replaced, because if there is not enough oxaloacetate available to form citrate the rate of acetyl CoA metabolism, and hence the rate of formation of ATP, will slow down. As shown in Figure 5.20, a variety of amino acids give rise to citric acid cycle intermediates, so replenishing cycle intermediates and permitting the removal of oxaloacetate for gluconeogenesis. In addition, the reaction of pyruvate carboxylase (see Figure 5.20) is a major source of oxaloacetate to maintain citric acid cycle activity.

There is a further control over the removal of oxaloacetate for gluconeogenesis. As shown in Figure 5.18, the decarboxylation and phosphorylation of oxaloacetate to form phosphoenolpyruvate uses GTP as the phosphate donor. In tissues such as liver and kidney, which are active in gluconeogenesis, the major source of GTP in the mitochondria is the reaction of succinyl CoA synthetase. If so much oxaloacetate were withdrawn that the rate of cycle activity fell, there would be inadequate GTP to permit further removal of oxaloacetate. In tissues such as brain and heart, which do not carry out gluconeogenesis, there is a different isoenzyme of succinyl CoA synthetase, which is linked to phosphorylation of ADP rather than GDP

Supplements For Diabetics

Supplements For Diabetics

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