SOME METABOLIC PRECURSORS OF THE N-1-METHYL GROUP OF ANSERINE IN THE RAT

Abstract

In support of the view that methylhistidine is a metabolic precursor of anserine, Martignoni and Winnick (1) and Harms and Winnick (2) found that administration of unlabeled 1-methyl-DL-histidine enhanced the incorporation of ft-alanine-l-C 4 into anserine in the chick and that 1-methyl-DL-histidine-C'4OOH was readily incorporated into anserine.In the rat, labeled 1-methylhistidine was utilized little, if at all, for anserine synthesis, but there was evidence that methylation of carnosine to form anserine could occur.That methionine may serve as the methyl donor was demonstrated earlier by Schenck et al. (3), who showed a transfer of deuteromethyl groups from methionine to anserine in the rabbit.However, the role of formate and formaldehyde, both well known as methyl precursors in a number of reactions (4-13), has not been evaluated in anserine synthesis.The present investigation describes the isolation of anserine and the related peptide, carnosine, from rat skeletal muscle by a modification of the chromatographic method of Hirs, Moore, and Stein (14) and presents data which demonstrate that, in the rat in vivo, methionine-methyl-C1 4 is utilized about 20 times more efficiently than is formate-C 4 or formaldehyde-C14 for the synthesis of the N-1-methyl group of anserine. EXPERIMENTALGeneral Experimental Procedure-Rats of the Sprague-Dawley strain (150 to 210 gm.), which had been fed Purina laboratory chow ad libitum, were injected intraperitoneally with doses of 6 moles of L-methioninemethyl-C 4 (1.2 X 106 c.p.m.),' 23 moles of sodium formate-C 1 4 (2.3 X 106 * A preliminary report of this investigation was presented before the Fortyseventh annual meeting of the American Society of Biological Chemists at Atlantic City, April 16-20, 1956.l L-Methionine-methyl-C14 (2 X 108 c.p.m. per mmole) was purchased from the Isotopes Specialties Company, Inc., Glendale, California; sodium formate-C 1 4 (1 X 108 c.p.m. per mmole) from Tracerlab, Inc., Boston, Massachusetts; and formaldehyde-C 4 (1 X 10' c.p.m. per mmole) from the Research Specialties Company, Berkeley, California.