Metabolism of Dl-Glutamic Acid-2-C14 by the Rat

Although the enzymatic reactions necessary to convert a-ketoglutarate to oxalacetate and acetate (via citrate) have been shown to be reversible in vitro ( 1), there appears to be no evidence concerning such a reversal in vivo.In attempting to demonstrate such a reversal in vivo we have administered DL-glutamic acid-2-C 4 to normal and fluoroacetate-poisoned rats.The labeling patterns found in aspartic acid, glutamic acid, serine, and alanine isolated from the tissues of the normal animals clearly demonstrate a pathway of glutamate catabolism other than direct conversion to succinate via a-ketoglutarate.This pathway is not functional in rats poisoned with fluoroacetate.EXPERIMENTAL Male albino rats (of Wistar origin) from our own colony were used in these investigations.The DL-glutamic acid-2-CI 4 (0.4 mc. per mmole) used was obtained from Isotopes Specialties Company, Inc. Degradation by the authors showed that significant radioactivity was present only in carbon 2.1 The isotopic material was dissolved in 1 to 2 ml. of physiological saline and administered by intraperitoneal injection.During the 4 hour period between injection and killing, the animals were placed in an all-glass metabolism chamber which was swept with a slow stream of air.The expired CO 2 was trapped in alkali.Data concerning the quantities of glutamic acid injected are given in Table I.All the animals were fed Purina checkers ad libitum before and during the experimental period.Rats 21 and 22 received 3.5 mg. of sodium fluoroacetate (2) per kilo of body weight 3 hours prior to the glutamic acid injection, the fluoroacetate being administered by intraperitoneal injection of an aqueous solution (0.35 mg. per ml.).The animals receiving fluoroacetate were hypersensitive to noise and physical contact, and both animals experienced tetany during the experiment, Rat 21 having several severe convulsions.