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Identification of a Transaminative Pathway for Ethionine Catabolism¹

Departments of Nutritional Sciences and Meat and Animal Science, University of Wisconsin, Madison, Wisconsin 53706

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-[ethyl-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 -keto acid of ethionine as the phenylhydrazone derivative. The addition of 3-ethylthiopropionate to the incubations resulted in complete inhibition of ¹⁴CO₂ formation from 10 mM L-[ethyl-1-¹⁴C]ethionine. The expanded 3-ethylthiopropionate pool was isolated by anion-exchange chromatography to determine if it had become labeled during the incubation. Gas-liquid chromatography of the isolated products revealed a major radioactive 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-ethylthiopropionate. The same gas chromatograph peak and mass spectra were obtained when a boiled liver homogenate was incubated with L-[ethyl-1-¹⁴C]ethionine and an expanded 3-ethylthiopropionate pool; however, as expected, the peak recovered from the gas chromatograph was not radioactive. These results indicate that 3-ethylthiopropionate is formed, probably as a result of decarboxylation of the -keto acid of ethionine and is thus an intermediate in ethionine catabolism. Rats fed a diet containing 1.5% of 3-ethylthiopropionate exhibited 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. Experiments with the liver homogenate system demonstrated the formation of labeled ethanethiol in addition to ¹⁴CO₂ from 10 mM [ethyl-1-¹⁴C]-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.

¹ This work was supported by funds from the College of Agricultural and Life Sciences and by Grant AM 15227 from the NIH. A preliminary report of this work has appeared (40). Department Manuscript 727.

² Present address: Department of Nutrition, Rutgers University, New Brunswick, N. J. 08903.

³ To whom requests for reprints should be addressed.

Received 4/19/79. Accepted 6/22/79.