DBT (gene)

DBT, also known as dihydrolipoyltransacylase (also known as dihydrolipoyl transacylase or lipoamide acyltransferase), is a gene that encodes the E2 subunit of the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex. This complex is a mitochondrial enzyme involved in the catabolism of branched-chain amino acids (BCAAs) - leucine, isoleucine, and valine.

The BCKDH complex is comprised of three catalytic components: E1 (branched-chain alpha-keto acid decarboxylase), E2 (dihydrolipoyltransacylase), and E3 (dihydrolipoyl dehydrogenase). The DBT gene specifically provides instructions for making the E2 component. The E2 component acts as a core structural component, providing the binding site for E1 and E3 and also catalyzes the transacylation reaction in the BCAA catabolic pathway.

Mutations in the DBT gene can lead to Maple Syrup Urine Disease (MSUD), a rare inherited metabolic disorder characterized by the accumulation of BCAAs and their corresponding alpha-keto acids in the blood and urine. MSUD can result in neurological damage, feeding difficulties, and if left untreated, can be fatal. Different mutations in the DBT gene can result in varying degrees of enzyme deficiency and therefore, different severities of MSUD.

The DBT gene is located on chromosome 1 at position 1p31.1. Several transcript variants encoding different isoforms have been found for this gene.