Carbon atom 2 of L-histidine-2-C14, a source of the carbon of labile methyl groups in liver.

Data presented in this report point to carbon at.om 2 of L-histidine as an important source of the carbon of labile methyl groups. The results obtained in direct studies of the isolated perfused normal and cirrhotic rat liver are qualitatively and quantitatively similar t,o those obtained with intact normal rats and rats kept on a choline-deficient diet (1) for a short time (10 days) and a long time (1 year), the latt,er rats developing cirrhosis aft,er 3 to 4 months. While this work was in progress, several brief reports appeared focusing attention on the metabolic r&e of carbon atom 2 of L-histidine. saucy and Bouthillier (2) fed L-histidine-2-C14 to rats and found 25 to 33 per cent of the radioactivity of the liver protein hydrolysates to be in the serine recovered from these hydrolysat,es. Of the radioactivity found in similar hydrolysates of the combined remaining tissues, 9 to 14 per cent was recovered in serine. Reid and Landefeld (3) presented data indicating the use of carbon atom 2 of L-histidine for the synthesis of purines and the methyl groups of creatine and choline. In an earlier study in which L-histidine labeled with N15 in the y-nitrogen of the imidazole ring was employed, Tesar and Rittenberg (4) were unable to find any evidence for the r&e of histidine as a precursor of creatine or purines. The work reported in this paper was started under the stimulus of a preliminary report by Coon and Levy (5), lat,er followed by a more complete presentation (6), in which formate was found to be an effective precursor of histidine in yeast. Edlbacher (7) demonstrated a rat liver enzyme which opened the imidazole ring of histidine to give a product which yielded formate, probably from carbon atom 2, upon acid hydrolysis. Mackenzie (8), in discussing his finding formaldehyde and formic acid on oxidation of C14-methyl-labeled sarcosine by liver homogenates and slices,