Ketogenic amino acid transamination

Lysine, an exclusively ketogenic amino acid, is unusual in that nei ther of its amino groups undergoes transamination as the first step in catabolism. Lysine is ultimately converted to acetoacetyl CoA. 

Transamination reactions produce pyruvate, and deamination followed by degradation of the carbon skeleton of ketogenic amino acids produces acetyl-CoA (see Chap. 15). 

It is formed from the carboxylation of pyruvate and, to a lesser degree, from the deamination of aspartate or through the metabolic conversion of other ketogenic amino acids through a pathway involving transamination and successive oxidation from succinate to fumar-ate and malate. 

Norvaline is strongly ketogenic. The L-form is attacked by L-amino acid oxidase and the D-form by D-amino acid oxidase. Its susceptibility to transamination has not been reported. Its ready oxidation to CO2 in the intact animal has been observed by Hassan and Greenberg. More of this amino acid is excreted unchanged in the urine than is leucine. Evidence for the formation of a 2-carbon unit was also obtained in this work. This leads to the scheme for the catabolism of norvaline shown in Fig. 8. 

The catabolism of lysine merges with that of tryptophan at the level of (3-ketoadipic acid. Both metabolic pathways are identical from this point on and lead to the formation of acetoacetyl-CoA (Figure 20.21). Lysine is thus ketogenic. It does not transaminate in the classic way. Lysine is a precursor of carnitine the initial reaction involves the methylation of e-amino groups of protein-bound lysine with SAM. The N-methylated lysine is then released proteolytically and the reaction sequence to carnitine completed. See Equation (19.6) for the structure of carnitine. 

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