Which enzyme catalyzes the oxidative deamination of glutamate, producing α-ketoglutarate and ammonia, and is unique in accepting multiple amino acids as substrates?

Explanation

## Glutamate Dehydrogenase (GDH) **Key Point:** Glutamate dehydrogenase is the only enzyme that catalyzes oxidative deamination and is unique in its ability to accept multiple amino acids as substrates, making it a central hub in amino acid catabolism. ### Reaction Catalyzed $$\text{Glutamate} + NAD^+ (\text{or NADP}^+) \rightarrow \alpha\text{-Ketoglutarate} + NH_4^+ + NADH$$ ### Key Features of GDH 1. **Bidirectional reaction** — can catalyze both oxidative deamination and reductive amination 2. **Cofactor flexibility** — uses both NAD+ and NADP+ as electron acceptors 3. **Substrate specificity** — accepts glutamate as primary substrate, but also other amino acids (alanine, aspartate) at lower rates 4. **Mitochondrial localization** — found in the mitochondrial matrix 5. **Regulatory control** — allosterically regulated by ATP (inhibitor), ADP (activator), and GTP (inhibitor) ### Role in Nitrogen Metabolism **High-Yield:** GDH is the major enzyme for: - **Ammonia release** from amino acids into the bloodstream - **Ammonia fixation** during amino acid synthesis - **Link between carbohydrate and amino acid metabolism** via α-ketoglutarate (TCA cycle intermediate) ### Distinction from Other Deamination Enzymes | Enzyme | Type | Cofactor | Substrate Specificity | Product | |--------|------|----------|----------------------|----------| | **Glutamate dehydrogenase** | Oxidative | NAD+/NADP+ | Multiple amino acids | α-Ketoglutarate + NH₄⁺ | | **Alanine aminotransferase** | Transamination | PLP | Alanine (transfers amino group) | Pyruvate (not deamination) | | **Monoamine oxidase** | Oxidative | FAD | Monoamines (serotonin, dopamine) | Aldehydes + NH₃ | | **Serine dehydratase** | Non-oxidative | PLP | Serine | Pyruvate + NH₃ | **Mnemonic:** GDH = **G**lutamate **D**ehydrogenase **H**as **H**igh specificity for **H**ubbing multiple amino acids **Clinical Pearl:** Elevated serum GDH activity indicates hepatocellular injury, as GDH is predominantly found in liver mitochondria and is released upon cell damage. [cite:Lehninger Principles of Biochemistry Ch 22]