Complete oxidation of four and fivecarbon compounds

Although the citric acid cycle is generally regarded as a pathway for the oxidation of four- and five-carbon compounds arising from amino acids, such as fumarate, oxaloacetate, a-ketoglutarate and succinate (see Figure 5.20), it does not, alone, permit complete oxidation of these compounds. Four-carbon intermediates are not overall consumed in the cycle, as oxaloacetate is reformed. Addition of four- and five-carbon intermediates will increase the rate of cycle activity (subject to control by the requirement for ATP) only until the pool of intermediates is saturated.

Complete oxidation of four- and five-carbon intermediates requires removal of oxaloacetate from the cycle, and conversion to pyruvate, as shown in Figure 5.20. This pyruvate may either undergo decarboxylation to acetyl CoA (see Figure 5.16), which can be oxidized in the cycle, or may be used as a substrate for gluconeogenesis.

Oxidation of four- and five-carbon citric acid cycle intermediates thus involves a greater metabolic activity than oxidation of acetyl CoA. This has been exploited as a means of overcoming the hypothermia that occurs in patients recovering from anaesthesia, by giving an intravenous infusion of the amino acid glutamate. This provides a-ketoglutarate, which will largely be used for gluconeogenesis, and hence causes an increase in metabolic activity and increased heat production.

phospho-enolpyruvatt carboxykinase asparagine -> aspartate asparagine -> aspartate phenylalanine -ยป tyrosine glucose f , gluconeogenesis j , glycolysis , {

phospho-enolpyruvate glucose f , gluconeogenesis j , glycolysis , {

phospho-enolpyruvate phospho-enolpyruvatt carboxykinase asparagine -> aspartate

malate isocitrate malate fumarate isocitrate ketoglutarate -

succinate CoASH

succinate CoASH

succinyl CoA"

serine <- glycine cysteine <- methionine alanine <- tryptophan tyrosine <- phenylalanine tryptophan leucine isoleucine lysine ornithine arginine proline histidine glutamine

glutamate valine isoleucine methionine

Figure 5.20 The entry of amino acid carbon skeletons into the citric acid cycle for gluconeogenesis.

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