Metabolism — citric acid cycle (step 6)
Succinate dehydrogenase: FAD-mediated oxidation
How the Succinate 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: Succinate, covalent FAD, active-site base. Conditions: Inner mitochondrial membrane (Complex II). Bonds formed: C=C (fumarate); FADH₂; bonds broken: two C–H. Stereochemistry: Trans (E) alkene: fumarate, never maleate. Rate and selectivity: Electrons pass to ubiquinone through Fe–S centres.
At a glance
Step 1: Base takes H⁺, FAD takes H⁻ equivalent
FAD, covalently anchored to the enzyme, abstracts a hydride-equivalent (as two sequential single-electron/proton transfers, or a concerted hydride, depending on mechanism) from succinate's alpha carbon, while a base removes the adjacent beta proton — a concerted, syn-periplanar dehydrogenation.
Step 2: Concerted dehydrogenation
This is mechanistically a syn-elimination forming a new C=C bond, directly parallel to the Chugaev and Cope eliminations covered earlier, just with FAD as the electron acceptor instead of a leaving group departing.
Step 3: Fumarate + FADH₂
The product is fumarate, with FAD reduced to FADH₂ — this is the only citric acid cycle enzyme embedded directly in the inner mitochondrial membrane, feeding its electrons straight into the electron transport chain as Complex II rather than needing to shuttle NADH there first.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- NADH
- Nicotinamide adenine dinucleotide (reduced). Hydride-donating coenzyme.
- FAD
- Flavin adenine dinucleotide. Two-electron/one-electron redox coenzyme.
How it compares with related reactions
| Succinate dehydrogenase | Aconitase | Citrate synthase | |
|---|---|---|---|
| Reagents | Succinate, covalent FAD, active-site base | Citrate, [4Fe-4S] cluster (Fe₄ binds OH), enzyme base (Ser) and acid | Acetyl-CoA, oxaloacetate, citrate synthase (His274, His320, Asp375) |
| Conditions | Inner mitochondrial membrane (Complex II) | Mitochondrial matrix, pH ≈ 7.4, 37 °C | Mitochondrial matrix, pH ≈ 7.8, 37 °C |
| Stereochemistry | Trans (E) alkene: fumarate, never maleate | Anti elimination; the intermediate flips so water adds to the opposite carbon | Enolate attacks the si face of oxaloacetate; pro-S citrate |
| Rate / selectivity | Electrons pass to ubiquinone through Fe–S centres | Near-equilibrium; citrate:isocitrate ≈ 90:10 at equilibrium | Hydrolysis of citryl-CoA (ΔG°′ ≈ −32 kJ/mol overall) makes the step irreversible |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Succinate dehydrogenase?
Succinate, covalent FAD, active-site base. Conditions: Inner mitochondrial membrane (Complex II).
Which bonds are formed and which are broken?
Formed: C=C (fumarate); FADH₂. Broken: two C–H.
What is the stereochemical outcome?
Trans (E) alkene: fumarate, never maleate
What controls the rate or the selectivity?
Electrons pass to ubiquinone through Fe–S centres
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- Curved-arrow notation: rules and the mistakes students make