L3hydroxyacylCoA

L-3-hydroxyacyl-CoA is a thioester formed when a fatty acyl chain is attached to coenzyme A with a hydroxyl group on the beta (3) position. The designation L refers to the stereochemistry of the 3-hydroxy group, which is important for the activity of downstream enzymes in fatty acid metabolism. L-3-hydroxyacyl-CoA functions as an intermediate in β-oxidation, the cellular pathway that breaks down fatty acids to generate acetyl-CoA and reducing equivalents.

In the β-oxidation cycle, the acyl-CoA substrate undergoes a sequence of enzymatic steps. After the initial dehydrogenation to form a trans-Δ2-enoyl-CoA, enoyl-CoA hydratase adds a molecule of water across the double bond, producing L-3-hydroxyacyl-CoA. The L-3-hydroxyacyl-CoA is then oxidized by L-3-hydroxyacyl-CoA dehydrogenase (an NAD+-dependent enzyme) to generate 3-ketoacyl-CoA. Subsequent thiolytic cleavage by β-ketoacyl-CoA thiolase yields a shortened acyl-CoA and acetyl-CoA (or propionyl-CoA for odd-chain fatty acids), continuing the cycle until the fatty acid is completely degraded.

Cellular localization can vary with organism and substrate chain length. In animals, the β-oxidation cycle largely occurs in mitochondria, while peroxisomal steps handle very-long-chain fatty acids. The L-3-hydroxyacyl-CoA intermediate is a conserved feature of this pathway across aerobic organisms, reflecting the stereospecific nature of the enzymes involved.

Clinical relevance arises from defects in fatty acid oxidation, which can disrupt the production and turnover of L-3-hydroxyacyl-CoA and related intermediates, contributing to metabolic disorders. Diagnostic approaches often examine acyl-CoA derivatives or related acylcarnitines in metabolic screening.