Regulation of the pyruvate dehydrogenase complex during the aerobic/anaerobic transition in the development of the parasitic nematode, Ascaris suum

Abstract

The pyruvate dehydrogenase complex (PDC) occupies a pivotal position in the novel, anaerobic, mitochondrial metabolism of the parasitic nematode, Ascaris suum (Kita, 1992; Komuniecki and Komuniecki, 1995). Adult ascarid muscle mitochondria use unsaturated organic acids, instead of oxygen, as terminal electron-acceptors and acetate, propionate, succinate, and the 2-methyl branched-chain fatty acids, 2-methylbutyrate and 2-methylvalerate, accumulate as end products of carbohydrate metabolism. The tricarboxylic acid cycle is not operative and the NADH-dependent reductions of fumarate and 2-methyl branched-chain enoyl CoAs are coupled to site 1, electron-transport associated energy-generation (Kita, 1992; Ma et al., 1993). Most importantly, from the perspective of pyruvate metabolism, intramitochondrial NADH/NAD⁺ and acyl CoA/CoA ratios appear to be dramatically elevated, when compared to the corresponding aerobic organelles, and serve as the driving force for the reversal of β–oxidation and the synthesis of branched-chain fatty acids (Kita, 1992; Komuniecki and Komuniecki, 1995). Therefore, it was initially surprising to find a functional PDC and PDH_a kinase in these organelles, given the potential for these elevated ratios to reduce PDC activity, either through end product inhibition or stimulation of PDH_a kinase and its subsequent phosphorylation and inactivation of the complex. In fact, the PDC is significantly overexpressed in adult ascarid muscle mitochondria and is present in amounts substantially greater than those reported from other eukaryotic sources (Song and Komuniecki, 1994; Thissen et al., 1986). Not surprisingly, both its subunit composition and regulatory properties differ significantly from complexes isolated from aerobic tissues.