Biogenesis of L-glyceric aciduria, oxalosis and renal injury in rats simulating type II primary hyperoxaluria.
Tracer experiments in rats mimicking type II primary hyperoxaluria, with an expanded intracellular pool of hydroxypyruvate, showed that the excess formation of oxalate did not originate from its immediate precursor glyoxylate. In these animals, the hepatic and kidney activities of oxalate synthesising enzymes such as lactate dehydrogenase and glycolate oxidase were normal, but tissue lipid peroxidation was significantly higher. In vitro experiments established that in a mild alkaline solution, hydroxypyruvate underwent auto-oxidation to form oxalate and H2O2 and also inhibited lactate dehydrogenase and glycolate oxidase from oxidising glyoxylate to oxalate. On the basis of the experimental evidence, we suggest that in type II primary hyperoxaluria, the accumulating hydroxypyruvate could reduce the intracellular pool of glyoxylate and on ageing, give rise to excess oxalate and H2O2, to cause oxalosis in the former and free radical mediated-cell injuries in the latter.
Raghavan
K G
KG
Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, India.
Lathika
K M
KM
Gandhi
N M
NM
D'Souza
S J
SJ
Tarachand
U
U
Ramakrishnan
V
V
Singh
B B
BB
D000818:Animals; D005988:Glyceric Acids / Q000378:metabolism*; D006038:Glyoxylates / Q000378:metabolism; D006959:Hyperoxaluria / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D010070:Oxalates / Q000378:metabolism*; D019815:Oxalic Acid; D051381:Rats; D017208:Rats, Wistar
D005988:Glyceric Acids; D006038:Glyoxylates; D008054:Lipid Peroxides; D010070:Oxalates; C042971:glyceric acid; D019815:Oxalic Acid; D007770:L-Lactate Dehydrogenase; C031150:glyoxylic acid