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Deuterium surface coil NMR study of the metabolism of D-methionine in the liver of the anesthetized rat

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00420a042· OSTI ID:6499534
The hepatic metabolism of deuteriated D-methionine has been studied in the intact, anesthetized rat using 2H NMR spectroscopy. The rate of formation of the principal labeled metabolite, (methyl-2H3)sarcosine, from the D-(methyl-2H3)methionine precursor was found to be as rapid as the rate observed previously in NMR studies of the hepatic metabolism of L-methionine. Similarly, rates of clearance of labeled methionine from the liver, formation of N-trimethyl-labeled metabolites, and labeling of the HDO pool were all found to be similar to the rates observed in the L-methionine studies. In contrast, all of these metabolic transformations are strongly inhibited by pretreatment of the rats with sodium benzoate, an inhibitor of D-amino acid oxidase. In vivo 2H NMR studies of sodium benzoate treated rats given L-(methyl-2H3)-methionine exhibit a much more rapid formation of (methyl-2H3)sarcosine than rats given the D enantiomer, consistent with the expectation that the sodium benzoate does not interfere with either the formation of S-adenosylmethionine or the subsequent transmethylation of glycine. However, the rates of methionine clearance and formation of deuteriated water are markedly reduced in this study relative to rats receiving the labeled D- or L-methionine without sodium benzoate pretreatment. These results indicate that subsequent to the initial oxidative deamination of the labeled D-methionine, the reamination to give L-methionine is rapid compared with the further degradation of the alpha-keto acid. Thus, the results are consistent with a dominant contribution of the glycine/sarcosine shuttle to the metabolism of excess D- or L-methionine.
Research Organization:
National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)
OSTI ID:
6499534
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:20; ISSN BICHA
Country of Publication:
United States
Language:
English