Trans-2-enoyl-CoA reductase (NAD+)

Trans-2-enoyl-CoA reductase (NAD+) (EC 1.3.1.44) is an enzyme that catalyzes the chemical reaction:

acyl-CoA + NAD⁺ ⇌ trans-2-enoyl-CoA + NADH + H⁺

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donors with NAD⁺ or NADP⁺ as acceptor. It participates in the metabolism of fatty acids, specifically in unsaturated fatty acid biosynthesis.

Nomenclature

The systematic name of this enzyme class is acyl-CoA:NAD⁺ 2-oxidoreductase. Other names in common use include:

• enoyl-CoA reductase (NAD⁺)
• NAD⁺-dependent enoyl-CoA reductase
• trans-2-enoyl-CoA reductase (NAD⁺-dependent)
• acyl coenzyme A dehydrogenase
• acyl CoA dehydrogenase
• acyl-CoA reductase
• enoyl-CoA reductase

Function

Trans-2-enoyl-CoA reductase (NAD+) is a key enzyme in the bacterial fatty acid synthesis pathway, specifically in the elongation cycle for unsaturated fatty acids. Unlike eukaryotic fatty acid synthesis which typically employs a multifunctional fatty acid synthase (FAS) complex, bacterial systems often use discrete enzymes for each step. This reductase plays a crucial role in converting trans-2-enoyl-CoA intermediates (formed during the synthesis of unsaturated fatty acids) back to acyl-CoA derivatives, allowing for further chain elongation. The enzyme requires NAD⁺ as a cofactor and generates NADH and a proton as byproducts. Its activity is essential for maintaining the pool of acyl-CoA building blocks necessary for fatty acid synthesis. The reaction it catalyzes is reversible.

Reaction Mechanism

The enzyme catalyzes the reduction of the double bond in trans-2-enoyl-CoA using NADH as the reducing agent. This results in the saturation of the double bond, producing acyl-CoA. The mechanism involves the transfer of a hydride ion from NADH to the β-carbon of the enoyl-CoA substrate, followed by protonation of the α-carbon.