Multiple Forms of Glutamate Dehydrogenase in Animals: Structural Determinants and Physiological Implications

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Glutamate dehydrogenase (GDH) is traditionally viewed as a mitochondrial enzyme.
• Recent findings reveal extramitochondrial GDH in the nucleus, endoplasmic reticulum, and lysosomes.
• These locations suggest moonlighting functions beyond metabolism.

Approach:

• This review synthesizes published data on animal GDH kinetics and localization.
• It considers splice variants, post-translational modifications, and isoenzymes in humans and apes.
• Comparative analysis with bovine brain GDH isoenzymes is included.

Key Points:

• Human GLUD1 and GLUD2 isoenzymes exhibit kinetic properties similar to bovine GDH1 and GDH2.
• Alternative splicing and post-translational modifications enhance GDH functional diversity and regulation.
• Thiamine derivatives emerge as novel modulators of GDH activity.
• Thiamine-dependent GDH regulation aligns with thiamine triphosphate generation during starvation.

Conclusions:

• Animal GDH exhibits diverse localization and functions beyond its canonical mitochondrial role.
• Structural variations in GDH isoforms, influenced by splicing and modifications, impact its regulation.
• Novel thiamine-dependent regulatory mechanisms for GDH are identified, linking nutrient status to enzyme activity.