Role of Hydroxypyruvate in the Manifestation of Primary Hyperoxaluria L-Glyceric Aciduria Type-II

  • K. G. Raghavan
  • K. V. Inamdar

Abstract

L-glyceric aciduria primary hyperoxaluria type II, a genetic disorder of oxalate metabolism in man, manifests due to the absence of the enzyme D-glycerate dehydrogenase that acts on hydroxypyruvate1. As a result, hydroxypyruvate (OHP) gets reduced to L-glyceric acid by the nonspecific action of lactate dehydrogenase (LDH) with concomitant oxidation of NADH to NAD. This increased formation of NAD is postulated to stimulate LDH to act favourably on glyoxylate and oxidize it to excess oxalate thus leading to secondary manifestation of hyperoxaluria2. While this hypothesis could explain both glyceric aciduria and hyperoxaluria, several questions remain unanswered. Whether OHP is reduced to D-glyceric acid by the enzyme D-glycerate dehydrogenase, as in normal individuals or reduced to L-glyceric acid by the enzyme LDH, as occurs in L-glyceric aciduria patients, the amount of NAD produced would be the same in both cases. Since NAD and NADH are common cofactors for other enzymic reactions also, it is difficult to visualize a selective role for NAD in inducing LDH to act on glyoxylate and convert it into oxalate. Unless glyoxylate, the main precursor of oxalate, is made available in excess amounts to LDH by some metabolic pathways, the excess formation of oxalate cannot be explained under such conditions. In view of these considerations we re-examined some of the experimental evidence that led to this hypothesis.

Keywords

HPLC Dioxide Lithium Lactate Cage 

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References

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    DW Fry and KE Richardson, Isolation and characterization of glycolic acid oxidase from human liver, BiochimBiophys Acta 568: 135 (1979).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • K. G. Raghavan
    • 1
  • K. V. Inamdar
    • 2
  1. 1.Radiation Biology and Biochemistry Division Bhabha Atomic Research CentreLTMM College & HospitalBombayIndia
  2. 2.Department of BiochemistryLTMM College & HospitalBombayIndia

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