S-21-1 Thiamine Responsive Pyruvate Dehydrogenase Deficiency

Abstract

The pyruvate dehydrogenase complex converts pyruvate to acetyl CoA within mitochondrial matrix and involves sequential activity of three enzyme components; pyruvate dehydrogenase (El), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3). The first component El is a tetramer of 2a and 2$ subunits and catalyzes the decarboxylation of pyruvate with thiamine pyrophosphate (TPP) as cofacter. Deficiency of El is the most common cause of congenital lactic acidosis. Thiamine therapy has been tried in some, but a patient reported by Wick et al in 19771 appears to be the only one who responded clinically and biochemically to thiamine therapy for a prolonged period. Although it has been proposed that the mechanism of its action is probably based on activation of El through interference in the physiologic regulation, the biochemical basis remains unclear. © 1992, Center for Academic Publications Japan. All rights reserved.