Metabolic pathways of homoserine in the mammal.

The importance of homoserine in the metabolism of amino acids in a variety of living forms is now well established. This amino acid was found to be the common precursor of methionine and threonine in Neurospora crassa (1). Enzymes involved in the conversion of aspartic acid to threonine via homoserine have been studied in Escherichia coli (2-5) and in bakers’ yeast (6-S). The presence of homoserine (9) and its derivatives (10, 11) has been demonstrated in various plants. In intact rats at least a part of the reported de nova synthesis of methionine seems to utilize the carbon skeleton of homoserine lactone (12). The metabolic formation of homoserine in mammals from methionine has been suggested from the study of the cleavage of cystathionine (13), and evidence for such conversion has been reported from this laboratory (14). In continuation of the studies on the metabolic fate of the main carbon chain of methionine, the investigation reported in this paper was undertaken in order to clarify the course of homoserine metabolism. Using nr,-homoserine-2-C14, we have been able to isolate and identify a-ketobutyric, cr-hydroxybutyric, ol-amino-n-butyric, and propionic acids by chromatographic means (cf. Figs. 1 and 2, and Table I). That homoserine is converted into a-ketobutyric acid in a rat liver system has been reported previously by Carroll, Stacy, and du Vigneaud (13), who isolated and identified the compound. The present study confirms this finding and also demonstrates that a-ketobutyric acid is aminated to a-aminobutyric acid, probably by transamination, and that glutamic acid is probably the principal, if not the sole, amino donor in the transamination. The effects of additions of glutamic acid and a-ketoglutaric acid to dialyzed and non-dialyzed rat liver enzyme systems are presented in Table I. This and our previous finding that homoserine is metabolically formed from methionine explain the observation of Dent (15) of an increased ex-