Identification of FAH domain containing protein 1 (FAHD1) as oxaloacetate decarboxylase [Metabolism]

January 9th, 2015 by Pircher, H., von Grafenstein, S., Diener, T., Metzger, C., Albertini, E., Taferner, A., Unterluggauer, H., Kramer, C., Liedl, K. R., Jansen-Durr, P.

Fumarylacetoacetate hydrolase (FAH) domain containing proteins occur both in prokaryotes and eukaryotes where they carry out diverse enzymatic reactions, probably related to structural differences in their respective FAH domains; however, the precise relationship between structure of the FAH domain and the associated enzyme function remains elusive. In mammals, three FAH domain containing proteins, FAHD1, FAHD2A and FAHD2B, are known; however, their enzymatic function, if any, remains to be demonstrated. In bacteria, oxaloacetate is subject to enzymatic decarboxylation; however, oxaloacetate decarboxylases (ODx) were so far not identified in eukaryotes. Based on molecular modeling and subsequent biochemical investigations, we identified FAHD1 as eukaryotic ODx enzyme. The results presented here indicate that dedicated oxaloacetate decarboxylases exist in eukaryotes.