DLAT

This gene encodes component E2 of the multi-enzyme pyruvate dehydrogenase complex (PDC). PDC resides in the inner mitochondrial membrane and catalyzes the conversion of pyruvate to acetyl coenzyme A. The protein product of this gene, dihydrolipoamide acetyltransferase, accepts acetyl groups formed by the oxidative decarboxylation of pyruvate and transfers them to coenzyme A. Dihydrolipoamide acetyltransferase is the antigen for antimitochondrial antibodies. These autoantibodies are present in nearly 95% of patients with the autoimmune liver disease primary biliary cirrhosis (PBC). In PBC, activated T lymphocytes attack and destroy epithelial cells in the bile duct where this protein is abnormally distributed and overexpressed. PBC enventually leads to cirrhosis and liver failure. Mutations in this gene are also a cause of pyruvate dehydrogenase E2 deficiency which causes primary lactic acidosis in infancy and early childhood.[provided by RefSeq, Oct 2009]

Full Name

Dihydrolipoamide S-Acetyltransferase

Function

The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2, and thereby links the glycolytic pathway to the tricarboxylic cycle.

Biological Process

Acetyl-CoA biosynthetic process from pyruvate Source: GO_Central
Glucose metabolic process Source: UniProtKB-KW
Sleep Source: Ensembl
Tricarboxylic acid cycle Source: UniProtKB-KW

Cellular Location

Mitochondrion matrix

Involvement in disease

Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex.
Pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency):
Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.

PTM

Delipoylated at Lys-132 and Lys-259 by SIRT4, delipoylation decreases the PHD complex activity.