Hydroxypyruvate-mediated regulation of oxalate synthesis by lactate dehydrogenase and its relevance to primary hyperoxaluria type II.
Hydroxypyruvate (HP) brought about the decarboxylation of [1-14C] glyoxylate nonenzymically at all pH values considered. The rate of decomposition of glyoxylate increased with each increase in the concentrations of the reactants, the pH, and temperature and on the addition of the cations Fe2+, Mn2+, Mg2+, Zn2+, Co2+, and Cu2+. The addition of HP to a purified preparation of lactate dehydrogenase (LDH) catalyzing the oxidation of [1-14C]glyoxylate to [14C]oxalate in the presence of either NAD or NADH inhibited the production of oxalate. These observations have their implications in L-glyceric aciduria (primary hyperoxaluria type II), a syndrome characterized by the accumulation of HP and recurrent oxalosis. They suggest that the accumulating HP may reduce the contribution of intracellular glyoxylate to the formation of oxalate by competitively inhibiting the liver LDH. The involvement of liver LDH in oxalate synthesis and its postulated induction by HP and NAD in vivo are, therefore, reexamined.
D000592:Amino Acid Metabolism, Inborn Errors / Q000209:etiology / Q000378:metabolism; D000818:Animals; D002412:Cations / Q000494:pharmacology; D002417:Cattle; D003653:Decarboxylation; D005988:Glyceric Acids / Q000652:urine; D006038:Glyoxylates / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D010070:Oxalates / Q000096:biosynthesis* / Q000652:urine; D011773:Pyruvates / Q000378:metabolism*; D011817:Rabbits
D002412:Cations; D005988:Glyceric Acids; D006038:Glyoxylates; D010070:Oxalates; D011773:Pyruvates; C012375:hydroxypyruvic acid; D007770:L-Lactate Dehydrogenase