Observations on sulfur amino acid deficiencies in rats; chemical and morphological changes in the blood.

The earliest indication for the need of an organic sulfur complex in the diet came in 1915 from the work of Osborne and Mendel (I), who showed that when the proportion of casein in the diet of the rat was reduced from 18 to 9 per cent the resulting impairment of growth could be corrected by a supplement of cystine equal to 3 per cent of the casein. This finding was confirmed in many laboratories and the rBle of cystine as a growth essential seemed definitely established. However, when in 1932 Jackson and Block (2) observed that methionine is also capable of supplementing a low casein ration, the growth essentiality of cystine was placed in doubt. Later Womack, Kemmerer, and Rose (3) using a synthetic mixture of nineteen amino acids as the protein moiety of an experimental diet concluded (a) that cystine is not a dietary essential for growth of the immature rat, (b) that its presence does not improve the quality of a ration which is adequate in methionine, and (c) that in the absence of methionine the administration of cystine fails to promote growth. These observations implied an irreversible conversion of methionine into cystine which has since been confirmed by the radioactive isotope investigations of Tarver and Schmidt (4). More recent. experiments by Womack and Rose (5) have shown that cystine is capable of stimulating growth only when methionine is present in suboptimal amounts and that only 16 per cent of the methionine requirements can be met by cystine. In apparent contradiction to these growth studies, an extensive study of the relationship of dietary cystine and methionine to the blood proteins led Whipple and coworkers (6) to conclude that methionine is not an efficient substitute for cystine in the regeneration of plasma proteins of experimentally hypoproteinemic dogs. These observations suggested that under certain conditions the rate of biological conversion of methionine is not