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.