^-Ketoglutarate ornithine proline histidine glutamine glutamate arginine valine isoleucine methionine

Figure 8 Entry of amino acid carbon skeletons into the tricarboxylic acid cycle. *These amino acids are ketogenic only. (Adapted with permission from Bender DA (2002) Introduction to Nutrition and Metabolism, 3rd edn. London: Taylor & Francis.)

Hence, the formation of glucose from noncarbohy-drate sources (gluconeogenesis) is important.

Glucose can be formed from the gluconeogenic amino acids and from glycerol released from the lipolysis of TAGs in adipose tissue. Amino acids can enter the TCA cycle as intermediates and be converted to oxaloacetate, the excess of which can then be removed and metabolized to phophoenol-pyruvate and then, by a process that is the reverse of glycolysis, be converted to glucose. Glycerol can be converted to an intermediate on the glycolytic pathway and therefore undergo gluconeogenesis if required.

Amino acids that can only be metabolized to acetyl-CoA cannot undergo gluconeogenesis because acetyl-CoA cannot be converted back to pyruvate and the inclusion of more acetyl-CoA will not generate a net increase in oxaloacetate, which can be removed from the cycle. Hence, fatty acids and ketones that are broken down into acetyl-CoA also cannot be used for gluconeogenesis.

There are three enzymes in gluconeogenesis that are different from those in glycolysis, and the relative activity of these compared to the equivalent glycolytic enzymes is tightly controlled by hormones, hence controlling whether glycolysis or glu-coneogenesis is the dominant pathway.

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