1NI4, 2OZL, 3EXE, 3EXF, 3EXG, 3EXH, 3EXI516018597ENSG00000131828ENSMUSG00000031299P08559Q5JPT9P35486NM_000284NM_001173454NM_001173455NM_001173456NM_008810NP_000275NP_001166925NP_001166926NP_001166927NP_032836Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial is an enzyme that in humans is encoded by the PDHA1 gene.The pyruvate dehydrogenase complex is a nuclear-encoded mitochondrial matrix multienzyme complex that provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle by catalyzing the irreversible conversion of pyruvate into acetyl-CoA.

The remaining 361 amino acids, starting at the N terminus with phenylalanine, represent the mature mitochondrial E1 alpha peptide.

Crystal Structures allowed for a model in which the enzyme undergoes a 2-A shuttle-like motion of its heterodimers to perform the catalysis.

This step is only one of the central metabolic pathway carried out by eukaryotes, in which glucose is oxidized to form carbon dioxide, water, and ATP.

As such, the absolute amounts of site-specific kinases and phosphates expressed in the mitochondria directly affect PDH activity.

The disorder is the direct result of steric clash between the new phosphate group at Ser-264 and another serine, Ser-266, which destabilizes the hydrogen-bonding network that keeps the loops in place.

Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems.

Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking.

Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.

[17][18][19] While most of the clinical presentation is homogenous with the general disease, some cases have been identified in which there was focal dilatation of the right lateral ventricle with unilateral periventricular leukomalacia (PVL) with subependymal cyst.