Vitamin B6 deficiency augments endogenous oxalogenesis after intravenous l-hydroxyproline loading in rats

Abstract

The effects of an intravenous hydroxyproline load on endogenous oxalogenesis were compared in rats fed 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 (control group) or a vitamin B6-deficient diet for 3 weeks. Then the animals were intravenously administered 100 mg (762.6 micromol)/ml hydroxyproline. In the control group, infusion of hydroxyproline increased the 5-h urinary oxalate and glycolate excretion above baseline to 0.27% (2.02 +/- 1.11 micromol) and 0.32% (2.43 +/- 1.60 micromol) of the administered dose (mol/mol), while it was respectively 2.01% (15.24 +/- 2.13 micromol) and 0.00% (-0.02 +/- 0.19 micromol) of the dose in the vitamin B6-deficient group. Therefore, vitamin B6 deficiency augmented endogenous synthesis of oxalate from hydroxyproline by 7.56-fold (15.24/2.02) compared with that in the control group. Urinary citrate excretion was significantly lower at baseline and all other times in the vitamin B6-deficient group compared with the control group. In conclusions, L-hydroxyproline loading augmented endogenous oxalogenesis in the vitamin B6-deficient group without causing hyperglycolic aciduria, and also led to significant hypocitraturia. These findings suggest that hydroxyproline is not metabolized to oxalate via glycolate, but rather via the 4-hydroxyglutamate to glyoxylate pathway (usually requiring vitamin B6-dependent enzymes) even in the presence of vitamin B6 deficiency.

Dietary Oxalate and Calcium Oxalate Nephrolithiasis

“…3,8,9 However, only a small proportion of HLP is metabolized and converted to Ox. 3,4,9,10 HLP consumption with food resulted in hyperoxaluria, CaOx crystalluria and nephrolithiasis in male Sprague- FIG. 5.…”

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

“…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.…”

“…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 .…”

“…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

“…Species such as man and rabbits expressing AGT1 almost exclusively in peroxisomes have lost the first translation start site during evolution resulting in an MTS-lacking protein. In cats and (61,69) ; II, conversion of glyoxylate into L-glycine catalysed by alanine:glyoxylate aminotransferase 1 (AGT1) (64,74,75,82,83,92,100,101,105) ; III, conversion of glyoxylate into glycolate catalysed by glyoxylate reductase/hydroxypyruvate reductase (GR/HPR) (67,68,69,72,155,156) ; IV, conversion of hydroxypyruvate into D-glycerate catalysed by glyoxylate reductase/hydroxypyruvate reductase (67,68,69,72,155,156) . Essential metabolic conversions in situation B are indicated with Ia -d, II, III and IV, meaning: Ia, conversion of cytosolic D-fructose, D-glucose and D-galactose into D-glycerate (86,87,89) ; Ib, conversion of D-glycerate into hydroxypyruvate; Ic, conversion of hydroxypyruvate into glycolaldehyde (80) ; Id, conversion of glycolaldehyde into glycolate (80) ; II, conversion of peroxisomal glycolate into oxalate catalysed by glycolate dehydrogenase (GD) (97) ; III, conversion of peroxisomal glycolate into glyoxylate catalysed by glycolate oxidase (GO) (97) ; IV, conversion of glyoxylate into L-glycine catalysed by alanine:glyoxylate aminotransferase 1 (64,74,75,101,157) .…”