Metabolism — amino acid catabolism
Glutamate dehydrogenase: oxidative deamination
How the Glutamate dehydrogenase works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: L-Glutamate, NAD⁺ or NADP⁺, H₂O. Conditions: Mitochondrial matrix, glutamate dehydrogenase; reversible. Bonds formed: C=N⁺ then C=O; NADH; NH₄⁺; bonds broken: α C–H; C–N. Stereochemistry: Hydride to one face of nicotinamide; planar iminium loses α-stereochemistry. Rate and selectivity: Allosterically regulated: ADP/GDP activate, ATP/GTP inhibit.
At a glance
Step 1: Hydride transfer gives iminium
Glutamate's alpha-amino carbon is oxidized by NAD⁺ (or NADP⁺) — a hydride transfers from that carbon to the cofactor, forming an iminium ion, the same hydride-transfer logic as every other NAD⁺-linked dehydrogenase in this library, just applied to a C–N bond instead of a C–O bond.
Step 2: Water adds to the iminium
Water attacks this iminium ion's electrophilic carbon — ordinary nucleophilic addition to an activated imine, forming a tetrahedral carbinolamine intermediate.
Step 3: Collapse releases NH₄⁺
Collapse of that intermediate releases free ammonium ion and α-ketoglutarate — this reaction is the primary gateway feeding amino groups from protein catabolism into the urea cycle for disposal, while the carbon skeleton (α-ketoglutarate) feeds directly back into the citric acid cycle covered earlier.
Abbreviations and terms
- L
- Ligand. A Lewis-base group (often a phosphine) bound to a metal centre.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- ATP
- Adenosine triphosphate. The cell’s energy currency; transfers phosphate groups.
- ADP
- Adenosine diphosphate. ATP after losing one phosphate.
- NAD+
- Nicotinamide adenine dinucleotide (oxidised). Hydride-accepting coenzyme in oxidations.
- NADH
- Nicotinamide adenine dinucleotide (reduced). Hydride-donating coenzyme.
- NADP
- NADP⁺ / NADPH. Phosphorylated NAD cousin used mainly in biosynthetic reductions.
How it compares with related reactions
| Glutamate dehydrogenase | Fatty acid β-oxidation cycle | Aconitase | |
|---|---|---|---|
| Reagents | L-Glutamate, NAD⁺ or NADP⁺, H₂O | Acyl-CoA, FAD, H₂O, NAD⁺, CoA-SH | Citrate, [4Fe-4S] cluster (Fe₄ binds OH), enzyme base (Ser) and acid |
| Conditions | Mitochondrial matrix, glutamate dehydrogenase; reversible | Mitochondrial matrix; acyl-CoA dehydrogenase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, thiolase | Mitochondrial matrix, pH ≈ 7.4, 37 °C |
| Stereochemistry | Hydride to one face of nicotinamide; planar iminium loses α-stereochemistry | trans-Δ² enoyl-CoA; L-3-hydroxyacyl-CoA | Anti elimination; the intermediate flips so water adds to the opposite carbon |
| Rate / selectivity | Allosterically regulated: ADP/GDP activate, ATP/GTP inhibit | Each turn shortens the chain by two carbons | Near-equilibrium; citrate:isocitrate ≈ 90:10 at equilibrium |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Glutamate dehydrogenase?
L-Glutamate, NAD⁺ or NADP⁺, H₂O. Conditions: Mitochondrial matrix, glutamate dehydrogenase; reversible.
Which bonds are formed and which are broken?
Formed: C=N⁺ then C=O; NADH; NH₄⁺. Broken: α C–H; C–N.
What is the stereochemical outcome?
Hydride to one face of nicotinamide; planar iminium loses α-stereochemistry
What controls the rate or the selectivity?
Allosterically regulated: ADP/GDP activate, ATP/GTP inhibit
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- Curved-arrow notation: rules and the mistakes students make