title: Multiple Forms of Glutamate Dehydrogenase in Animals: Structural Determinants and Physiological Implications.
abstract: Glutamate dehydrogenase (GDH) of animal cells is usually considered to be a mitochondrial enzyme. However, this enzyme has recently been reported to be also present in nucleus, endoplasmic reticulum and lysosomes. These extramitochondrial localizations are associated with moonlighting functions of GDH, which include acting as a serine protease or an ATP-dependent tubulin-binding protein. Here, we review the published data on kinetics and localization of multiple forms of animal GDH taking into account the splice variants, post-translational modifications and GDH isoenzymes, found in humans and apes. The kinetic properties of human GLUD1 and GLUD2 isoenzymes are shown to be similar to those published for GDH1 and GDH2 from bovine brain. Increased functional diversity and specific regulation of GDH isoforms due to alternative splicing and post-translational modifications are also considered. In particular, these structural differences may affect the well-known regulation of GDH by nucleotides which is related to recent identification of thiamine derivatives as novel GDH modulators. The thiamine-dependent regulation of GDH is in good agreement with the fact that the non-coenzyme forms of thiamine, i.e., thiamine triphosphate and its adenylated form are generated in response to amino acid and carbon starvation.
authors.affiliation: A.N.Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Moscow 19991, Russia. bunik@belozersky.msu.ru.|Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 19991, Russia. bunik@belozersky.msu.ru.
authors.forename: Victoria
authors.initials: V
authors.lastname: Bunik
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 19991, Russia. whitelord32br@gmail.com.
authors.forename: Artem
authors.initials: A
authors.lastname: Artiukhov
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 19991, Russia. Aleshin_vasily@mail.ru.
authors.forename: Vasily
authors.initials: V
authors.lastname: Aleshin
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 19991, Russia. g.v.mkrtchyan@gmail.com.
authors.forename: Garik
authors.initials: G
authors.lastname: Mkrtchyan
keywords: acetylation; adenylated thiamine triphosphate; glutamate dehydrogenase alternative splicing; glutamate dehydrogenase isoenzymes; glutamate dehydrogenase isoforms; nucleotide-dependent regulation