Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, Innsbruck A-6020, Austria
Center for Molecular Biosciences Innsbruck (CMBI), Innsbruck, Austria.
Biochem Soc Trans. 2018 Apr 17;46(2):295-309. doi: 10.1042/BST20170518. Epub 2018 Feb 27.
Prokaryotic and eukaryotic fumarylacetoacetate hydrolase (FAH) superfamily members, sharing conserved regions that form the so-called FAH-domain, catalyze a remarkable variety of reactions. These enzymes are essential in the metabolic pathways to degrade aromatic compounds in prokaryotes and eukaryotes. It appears that prokaryotic FAH superfamily members evolved mainly to allow microbes to generate energy and useful metabolites from complex carbon sources. We review recent findings, indicating that both prokaryotic and eukaryotic members of the FAH superfamily also display oxaloacetate decarboxylase (ODx) activity. The identification of human FAH domain-containing protein 1 as mitochondrial ODx regulating mitochondrial function supports the new concept that, during evolution, eukaryotic FAH superfamily members have acquired important regulatory functions beyond catabolism of complex carbon sources. Molecular studies on the evolution and function of FAH superfamily members are expected to provide new mechanistic insights in their physiological roles.
原核生物和真核生物延胡索酸乙酰乙酸水解酶（FAH）超家族成员，具有形成所谓 FAH 结构域的保守区域，催化着各种显著的反应。这些酶在原核生物和真核生物中降解芳香族化合物的代谢途径中是必不可少的。似乎原核生物 FAH 超家族成员的进化主要是为了让微生物能够从复杂的碳源中产生能量和有用的代谢物。我们回顾了最近的发现，表明 FAH 超家族的原核生物和真核生物成员都表现出草酰乙酸脱羧酶（ODx）活性。人类 FAH 结构域包含蛋白 1 作为调节线粒体功能的线粒体 ODx 的鉴定支持了这样一个新概念，即在进化过程中，真核生物 FAH 超家族成员已经获得了除了复杂碳源分解代谢之外的重要调节功能。FAH 超家族成员的进化和功能的分子研究有望为其生理作用提供新的机制见解。
