Perfused rat hindquarter preparations were shown to incorporate radioactivity from [U-14C]methionine into citrate-cycle intermediates, lactate, alanine, glutamate, glutamine and CO2. During perfusion, large amounts of methionine were also oxidized to methionine sulphoxide. The capacity for transamination of methionine or its oxo analogue, 4-methylthio-2-oxobutyrate, by muscle extracts was demonstrated. Rat skeletal muscle, heart, liver and kidney mitochondria, when incubated with the latter plus radiolabelled carnitine, formed a newly identified carnitine derivative, 3-methylthiopropionylcarnitine. It is concluded that the capaci-ty for oxidation of methionine by a trans-sulphuration-independent pathway occurs in several mammalian tissues. The extent of inter-organ handling of intermediates in this pathway(s) is discussed.
INTRODUCTIONA series of studies evaluating the ability of skeletal muscle to metabolize amino acids resulted in balance studies which indicated that, of the non-dispensable amino acids, not only the branched-chain amino acids were broken down, but methionine was as well [1,2]. Methionine is generally assumed not to be metabolized by muscle since the enzymes of the accepted catabolic pathway, the trans-sulphuration-trans-methylation pathway, are very weak, if not totally absent [3,4]. In recent years Benevenga and co-workers have championed the existence (studied in liver only) of an alternative pathway involving an initial transamination (see, e.g., [5] for review and earlier references). A trans-sulphurationindependent pathway of methionine metabolism is not mentioned in modern biochemistry texts, and is therefore largely ignored. The importance, or even existence, of such a pathway is met by some reviewers with scepticism [6,7]. However, for the present authors, evidence for the physiological importance of an alternate pathway of methionine catabolism (at least in liver) involving transamination and oxidative decarboxylation is compelling. This evidence is lucidly summarized by Livesey [8].In the present study we show that a rat skeletal-muscle preparation converts methionine carbon into citratecycle intermediates, lactate, glutamate, alanine and CO2. In addition, we report that incubation of 'oxomethionine' (4-methylthio-2-oxobutyrate) together with carnitine and mitochondria from four different rat tissues results in formation of 3-methylthiopropionylcarnitine. Hence it appears that 3-methylthiopropionyl-CoA is an intermediate in the breakdown of methionine in at least several tissues.