The metabolism of excess methionine in the liver of the intact rat: an in vivo deuterium NMR study

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Abstract
L-Methionine is the most toxic amino acid if supplied in excess, and the metabolic basis of this toxicity has been extensively studied, with varying conclusions. It is demonstrated here that in vivo 2H NMR spectroscopy provides a useful approach to the study of the hepatic metabolism of methionine in the anesthetized rat. Resonances corresponding to administered L-[methyl-2H3]methionine, and to the transmethylation product sarcosine, are observed during the first 10-min period after an intravenous injection of the labeled methionine, and the time dependence has been followed for a period of 5 h. A third resonance, assigned to the N-trimethyl groups of carnitine, phosphorylcholine, and other metabolites, become observable the intensity of the HDO resonance over the period of the study, which is interpreted to reflect the ultimate oxidation of the labeled sarcosine methyl group via mitochondrial sarcosine dehydrogenase. Additional small 2H resonances assigned to N1-methylhistidine and creatine could be observed in perchloric and extracts of the livers of rats treated with the deuteriated methionine. Inhibition of the flux through the transmethylation pathway is observed in the rat pretreated with S-ethyl analogue of methionine, ethionine. These data provide strong support for the importance of glycine transmethylation in the catabolism of excess methionine.