Identification of a Transaminative Pathway for Ethionine Catabolism1

The potential for the oxidation of ethionine by a transaminative route was studied in an attempt to elucidate the pathways whereby the ethyl carbons of ethionine are converted to carbon dioxide. Ethionine is transaminated based on the recovery of a radioactive phenylhydrazone derivative. Carbon 1 of the ethyl portion of ethionine is recovered as carbon dioxide when L[ef/jy/-1-14C]ethionine is incubated in a rat liver homogenate system. The addition of pyruvate as an amino group acceptor for transamination stimulated oxidation by more than 10-fold based on carbon dioxide formation and on recovery of the aketo acid of ethionine as the phenylhydrazone derivative. The addition of 3-ethylthiopropionate to the incubations resulted in complete inhibition of 14CO2formation from 10 rriM L-[efhy/-114C]ethionine. The expanded 3-ethylthiopropionate pool was isolated by anion-exchange chromatography to determine if it had become labeled during the incubation. Gas-liquid chro matography of the isolated products revealed a major radio active peak with a retention time identical to that of a reference sample of 3-ethylthiopropionate. Mass spectral analysis of this radioactive peak obtained from liver homogenate incubations was identical to the spectra obtained from authentic 3-ethyl thiopropionate. The same gas Chromatograph peak and mass spectra were obtained when a boiled liver homogenate was incubated with i_-[efhy/-1-14C]ethionine and an expanded 3ethylthiopropionate pool; however, as expected, the peak re covered from the gas Chromatograph was not radioactive. These results indicate that 3-ethylthiopropionate is formed, probably as a result of decarboxylation of the a-keto acid of ethionine and is thus an intermediate in ethionine catabolism. Rats fed a diet containing 1.5% of 3-ethylthiopropionate ex hibited severe depressions in growth and food intake and displayed marked neuromuscular abnormalities. Mortality was 40% over the 2-week experimental period. The animal's breath had an odor that was indistinguishable from ethanethiol. Ex periments with the liver homogenate system demonstrated the formation of labeled ethanethiol in addition to 14CO2from 10 HIM [ef/iy/-1-'4C]-3-ethylthiopropionate. This pathway appears to account for the majority of ethionine oxidation in a liver homogenate system. From these studies, it appears that this oxidative pathway may be intimately involved in the etiology of the many biochemical alterations that have been reported after ethionine administration.