Which enzyme catalyzes the first committed step of fatty acid β-oxidation in mitochondria?

Explanation

## Fatty Acid β-Oxidation: First Committed Step **Key Point:** Acyl-CoA dehydrogenase (ACD) catalyzes the oxidation of acyl-CoA to enoyl-CoA, removing two hydrogens and forming a double bond between the α and β carbons. This is the first committed step of β-oxidation proper. ### Why Acyl-CoA Dehydrogenase? **High-Yield:** Although acyl-CoA synthetase activates fatty acids to acyl-CoA in the cytoplasm, this is a preparatory step, not the first committed step of β-oxidation. Once inside the mitochondrial matrix (via carnitine shuttle), acyl-CoA dehydrogenase is the first enzyme of the four-step cycle. ### The Four-Step β-Oxidation Cycle | Step | Enzyme | Reaction | Product | |------|--------|----------|----------| | 1 | Acyl-CoA dehydrogenase | Oxidation (FAD → FADH₂) | Enoyl-CoA | | 2 | Enoyl-CoA hydratase | Hydration | 3-hydroxyacyl-CoA | | 3 | 3-hydroxyacyl-CoA dehydrogenase | Oxidation (NAD⁺ → NADH) | 3-ketoacyl-CoA | | 4 | 3-ketoacyl-CoA thiolase | Thiolysis | Acetyl-CoA + shortened acyl-CoA | **Clinical Pearl:** Deficiency of acyl-CoA dehydrogenase (particularly MCAD — medium-chain acyl-CoA dehydrogenase) causes hypoketotic hypoglycemia during fasting, as fatty acid oxidation is impaired. **Mnemonic:** **HEAT** — Hydroxyacyl, Enoyl, Acyl-CoA dehydrogenase, Thiolase (reverse order of the cycle).