Alterations in Renal Brush-Border-Membrane Enzymes in Vitamin A-, B1-, and B6-Deficient Rats
Hyperoxaluria is a common feature in patients with urolithiasis (1). To investigate the effect of vitamin deficiencies on oxalate metabolism, experimental hyperoxaluria was induced in male weanling rats by implementing vitamin A-, B1-, and B6-deficiencies. The present study was planned to evaluate the effect of hyperoxaluria on renal brush-border-membrane (BBM) hydrolytic enzymes. The specific activities of BBM marker enzymes, namely alkaline phosphatase (AP), leucine aminopeptidase (LAP), and gammaglutamyl transpeptidase (GGT) were assayed in normal and different hyperoxaluric conditions. A significant enhancement in urinary excretion of oxalate was observed in vitamin deficient rats (vitamin A, p<0.05; vitamin B1, p<0.01; and vitamin B6, p<0.001) as compared to their pair-fed controls. Vitamin-B1- and vitamin-B6-deficient rats showed a significant decrease in activities of LAP (p<0.01 and p<0.001, respectively) and AP (p<0.05 and p<0.001, respectively). However, in vitamin-A deficiency, only LAP was decreased (p<0.001). The Km and Vmax of these enzymes reveal that decreased activities of both AP and LAP in vitamin-B1 deficiency are, due to a lowering of the respective active-enzyme molecular numbers, indicating leaking of BBM enzymes in this deficiency. In pyridoxine deficiency, however, decreases in AP and LAP activities are due to a decreased affinity for their respective substrates which appears to be due to inhibition of both AP and LAP by oxalate. A significant increase in GGT (p<0.001) was observed only in thiamine deficiency, which is probably due to an enhanced turnover of enzyme rather than an increased affinity for the substrate. Thus, the present study reveals that hyperoxaluria induced in vitamin-B6 deficiency alters renal BBM enzymes due to inhibition by oxalate.