The metabolism and clinical relevance of the keto acid analogues of essential amino acids.

Essential amino acids are not themselves indispensible dietary requirements for the rat but their carbon skeletons are (Rose, 1938). With two exceptions, α-keto acid (Table 1) or α-hydroxy acid analogues maintain the growth of rats almost as well as the corresponding essential amino acids (Richards, 1972). Lysine and threonine are the exceptions: both are irreversibly deaminated (Neuberger & Sänger, 1944; Elliott & Neuberger, 1950) and although the final test of feeding their keto acid analogues has not been undertaken, the cr-hydroxy acid analogue of lysine failed to main­ tain growth (McGinty, Lewis & Marvel, 1924). Recently the clinical tail has wagged the bio­ chemical dog, provoking new interest in the extent to which man can synthesize essential amino acids from their analogues and in the possible thera­ peutic applications of essential amino acid analogues. Interest in the metabolism of essential amino acid analogues in man originally arose from the observations that about one-fifth of urea syn­ thesized is hydrolysed to ammonia in the gut (Walser & Bodenlos, 1959) and that both healthy and uraemic men can use ammonia nitrogen for protein synthesis (Richards, Metcalfe-Gibson,