When catabolism of carbon skeleton of amino acid occurs
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We now turn to the fates of the carbon skeletons of amino acids after the removal of the α-amino group. The strategy of amino acid degradation is to transform the carbon skeletons into major metabolic intermediates that can be converted into glucose or oxidized by the citric acid cycle. The conversion pathways range from extremely simple to quite complex. The carbon skeletons of the diverse set of 20 fundamental amino acids are funneled into only seven molecules: pyruvate, acetyl CoA, acetoacetyl CoA, α-ketoglutarate, succinyl CoA, fumarate, and oxaloacetate. We see here a striking example of the remarkable economy of metabolic conversions, as well as an illustration of the importance of certain metabolites.
Amino acids that are degraded to acetyl CoA or acetoacetyl CoA are termed ketogenic amino acids because they can give rise to ketone bodies or fatty acids. Amino acids that are degraded to pyruvate, α-ketoglutarate, succinyl CoA, fumarate, or oxaloacetate are termed glucogenic amino acids. The net synthesis of glucose from these amino acids is feasible because these citric acid cycle intermediates and pyruvate can be converted into phosphoenolpyruvate and then into glucose (Section 16.3.2). Recall that mammals lack a pathway for the net synthesis of glucose from acetyl CoA or acetoacetyl CoA.
Of the basic set of 20 amino acids, only leucine and lysine are solely ketogenic (Figure 23.21). Isoleucine, phenylalanine, tryptophan, and tyrosine are both ketogenic and glucogenic. Some of their carbon atoms emerge in acetyl CoA or acetoacetyl CoA, whereas others appear in potential precursors of glucose. The other 14 amino acids are classed as solely glucogenic. This classification is not universally accepted, because different quantitative criteria are applied. Whether an amino acid is regarded as being glucogenic, ketogenic, or both depends partly on the eye of the beholder. We will identify the degradation pathways by the entry point into metabolism.