Oxalate synthesis from hydroxypyruvate in vitamin-B6-deficient rats

Abstract

We studied the effects of an intravenous hydroxypyruvate load on endogenous oxalogenesis in rats receiving a standard diet or a vitamin-B6-deficient diet. Twelve male Wistar rats were randomized to two groups and were fed either a standard diet or a vitamin-B6-deficient diet for 3 weeks. Then the animals received an intravenous infusion of 100 mg/ml (960.6 micromol/ml) of hydroxypyruvate slowly over 10 min. Urine samples were collected just before hydroxypyruvate infusion and at hourly intervals until 5 h afterward. Urinary oxalate, glycolate, and citrate levels were measured by capillary electrophoresis. Hourly urinary oxalate excretion peaked within 2 h, while urinary glycolate excretion peaked at 1 h, after the hydroxypyruvate load in both control and vitamin-B6-deficient rats. Both urinary oxalate and glycolate excretion were higher in vitamin-B6-deficient rats than in control rats. Infusion of hydroxypyruvate increased the 5-h urinary oxalate and glycolate excretion to 0.68% (6.56 micromol) and 0.53% (5.10 micromol) of the administered dose (mol/mol), respectively, in the control rats, while oxalate and glycolate excretion, respectively, increased to 2.43% (23.36 micromol) and 0.79% (7.59 micromol) of the dose in the vitamin-B6-deficient rats. Urinary citrate excretion was significantly lower at baseline and all other times in the vitamin-B6-deficient rats than in the control rats. In conclusion, a hydroxypyruvate load increased endogenous oxalate synthesis in control rats, and its synthesis was even greater in vitamin-B6-deficient rats. Vitamin B6 deficiency also resulted in significant hypocitraturia.

Endogenous oxalogenesis after acute intravenous loading with ethylene glycol or glycine in rats receiving standard and vitamin B6‐deficient diets

“…The overall study protocol has been reported elsewhere 7,8 . Briefly, 24 male Wistar rats weighing 188.65 ± 6.10 g (mean ± SD) were randomly divided into two groups (an ethylene glycol group and a glycine group) of 12 animals each.…”

“…The method of sample collection has been explained elsewhere 7,8 . In short, hourly urine samples were collected by bladder puncture at 0 h and every hour subsequently until 5 h after infusion of ethylene glycol or glycine.…”

“…Oxalate is an end product of metabolism, and the oxalate excreted from the body is derived from both the diet and endogenous synthesis. In fact, a large portion of urinary oxalate is derived from endogenous metabolism of various oxalate precursors in the liver 1,6–8 . The chief immediate metabolic precursor of oxalate is glyoxylate, which is formed from glycolate in the peroxisomes and from hydroxyproline in the mitochondria, 7,9 so that oxalate synthesis is almost entirely dependent on the glyoxylate pathway.…”

“…A key reaction in this pathway is the conversion of glyoxylate to glycine coupled with the conversion of alanine to pyruvate catalyzed by the pyridoxal phosphate (vitamin B6)‐dependent enzyme alanine: glyoxylate aminotransferase (AGT) 6,9–11 . Among the various precursors of oxalate, hydroxypyruvate, hydroxyproline, ethylene glycol, glycolate, and glyoxylate have all been shown to significantly promote oxalogenesis, 7–9,12,13 whereas glycine and ascorbate do not increase urinary oxalate excretion in rats 14,15 …”

Influence of nutrition on feline calcium oxalate urolithiasis with emphasis on endogenous oxalate synthesis

“…Moreover, pyridoxine can act as a cofactor for various enzymes in the tricarboxylic acid cycle as well, leading to a decreased synthesis of citrate. Thus, under the condition of pyridoxine deficiency, citrate metabolism may be impaired, leading to a lower urinary citrate concentration and increased risk of precipitation with CaOx (103) . To the authors' knowledge, the effect of pyridoxine on urinary citrate excretion in cats has not been studied.…”