Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was conducted to investigate the effect of vitamin A, B1 and B6 deficiency on oxalate metabolism in rats. A significant hyperoxaluria was the common observation in all the three vitamin deficiencies (vitamin B6 greater than vitamin A greater than vitamin B1). The activities of hepatic glycolate oxidase and glycolate dehydrogenase were markedly enhanced in vitamin-A- and vitamin-B6-deficient rats. However, lactate dehydrogenase levels remained unaltered in these deficiencies as compared to their respective pair-fed controls. Vitamin B1 deficiency of 4 weeks' duration could augment the activity of glycolate oxidase only, with no alterations in the glycolate dehydrogenase and lactate dehydrogenase levels. Intestinal oxalate uptake studies revealed increased bio-availability of oxalate from the gut in vitamin-A- and vitamin-B6-deficient rats. Thus, the results suggest the relative contribution of both exogenous as well as endogenous oxalate in the process of calculogenesis under various nutritional stress conditions in rat.
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PMID:Comparative studies on the effect of vitamin A, B1 and B6 deficiency on oxalate metabolism in male rats. 236 74

Chronic vitamin B6 deficiency in male rats, 1, 2 and 3 months of age, led to increases in the activities of liver glycolate oxidase and kidney glycolate dehydrogenase as compared to pair-fed controls. Lactate dehydrogenase activity either decreased or showed no change in all three age groups. It is postulated that hyperoxaluria observed in vitamin B6 deficiency is due to two different pathways operative in the liver and kidney separately. A general increase seen in the enzyme activities of livers and kidneys of B6-deficient and pair-fed rats was age related.
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PMID:Vitamin B6 deficiency as related to oxalate-synthesizing enzymes in growing rats. 705 48

This study concerns the effect of an aqueous extract of Tribulus terrestris on the metabolism of oxalate in male rats fed sodium glycolate. Glycolate feeding resulted in hyperoxaluria as well as increased activities of oxalate synthesizing enzymes of the liver i.e. glycolate oxidase (GAO), glycolate dehydrogenase (GAD) and lactate dehydrogenase (LDH), and decreased kidney LDH activity. T. terrestris administration to sodium glycolate fed rats produced a significant decrease in urinary oxalate excretion, and a significant increase in urinary glyoxylate excretion, as compared to sodium glycolate fed animals. The supplementation of T. terrestris with sodium glycolate also caused a reduction in liver GAO and GAD activities, whereas liver LDH activity remained unaltered. The isoenzyme pattern of kidney LDH revealed that normalization of kidney LDH by T. terrestris feeding was mainly due to an increase in the LDH 5 fraction. The LDH 1 isoenzyme remained unchanged in all the groups.
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PMID:Effect of Tribulus terrestris on oxalate metabolism in rats. 785 65

Urinary oxalate plays an important role in the formation of calcium oxalate stone, and endogenous oxalate metabolism mainly occurs in the liver. Since dehydroepiandrosterone (DHEA) is known to have an effect on hepatocellular proliferation and on some hepatic enzymes, we examined the influence of DHEA on the activity of hepatic oxalate-related enzymes and on urinary oxalate excretion in rats. Fourteen male rats were castrated and divided into two groups. The control group was fed a standard diet, while the other rats were fed a diet containing 0.5% DHEA. After 4 weeks, the liver weight and the urinary levels of oxalate, glycolate, and glycine were significantly higher in the DHEA-treated rats than in the controls, while body weight did not differ between the two groups. Hepatic alanine:glyoxylate aminotransferase and glyoxylate reductase showed significantly higher activity in the DHEA-treated rats than in the controls, while glycolate oxidase activity was significantly reduced. Treatment with DHEA induced hyperoxaluria along with hepatocyte proliferation. This hyperoxaluria was probably caused by hepatocyte proliferation, but it could not be explained simply by the changes of hepatic oxalate-related enzymes. Investigation of the modulation of peroxisomal enzymes by peroxisomal proliferators or inhibitors may provide further insights into hepatocyte oxalate metabolism.
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PMID:Effect of dehydroepiandrosterone on oxalate metabolism in rats. 1497 51

Glycolate oxidase, a peroxisomal flavoenzyme, generates glyoxylate at the expense of oxygen. When the normal metabolism of glyoxylate is impaired by the mutations that are responsible for the genetic diseases hyperoxaluria types 1 and 2, glyoxylate yields oxalate, which forms insoluble calcium deposits, particularly in the kidneys. Glycolate oxidase could thus be an interesting therapeutic target. The crystal structure of human glycolate oxidase (hGOX) in complex with 4-carboxy-5-[(4-chlorophenyl)sulfanyl]-1,2,3-thiadiazole (CCPST) has been determined at 2.8 A resolution. The inhibitor heteroatoms interact with five active-site residues that have been implicated in catalysis in homologous flavodehydrogenases of L-2-hydroxy acids. In addition, the chlorophenyl substituent is surrounded by nonconserved hydrophobic residues. The present study highlights the role of mobility in ligand binding by glycolate oxidase. In addition, it pinpoints several structural differences between members of the highly conserved family of flavodehydrogenases of L-2-hydroxy acids.
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PMID:Structure of human glycolate oxidase in complex with the inhibitor 4-carboxy-5-[(4-chlorophenyl)sulfanyl]-1,2,3-thiadiazole. 2005 20

Primary hyperoxaluria type 1 (PH1), an inherited rare disease of glyoxylate metabolism, arises from mutations in the enzyme alanine-glyoxylate aminotransferase. The resulting deficiency in this enzyme leads to abnormally high oxalate production resulting in calcium oxalate crystal formation and deposition in the kidney and many other tissues, with systemic oxalosis and ESRD being a common outcome. Although a small subset of patients manages the disease with vitamin B6 treatments, the only effective treatment for most is a combined liver-kidney transplant, which requires life-long immune suppression and carries significant mortality risk. In this report, we discuss the development of ALN-GO1, an investigational RNA interference (RNAi) therapeutic targeting glycolate oxidase, to deplete the substrate for oxalate synthesis. Subcutaneous administration of ALN-GO1 resulted in potent, dose-dependent, and durable silencing of the mRNA encoding glycolate oxidase and increased serum glycolate concentrations in wild-type mice, rats, and nonhuman primates. ALN-GO1 also increased urinary glycolate concentrations in normal nonhuman primates and in a genetic mouse model of PH1. Notably, ALN-GO1 reduced urinary oxalate concentration up to 50% after a single dose in the genetic mouse model of PH1, and up to 98% after multiple doses in a rat model of hyperoxaluria. These data demonstrate the ability of ALN-GO1 to reduce oxalate production in preclinical models of PH1 across multiple species and provide a clear rationale for clinical trials with this compound.
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PMID:An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary Hyperoxaluria. 2953 12

Hyperoxaluria, excessive urinary oxalate excretion, is a significant health problem worldwide. Disrupted oxalate metabolism has been implicated in hyperoxaluria and accordingly, an enzymatic disturbance in oxalate biosynthesis can result in the primary hyperoxaluria. Alanine glyoxylate aminotransferase-1 and glyoxylate reductase, the enzymes involving glyoxylate (precursor for oxalate) metabolism, have been related to primary hyperoxalurias. Some studies suggest that other enzymes such as glycolate oxidase and alanine glyoxylate aminotransferase-2 might be associated with primary hyperoxaluria as well, but evidence of a definitive link is not strong between the clinical cases and gene mutations. There are still some idiopathic hyperoxalurias, which require a further study for the etiologies. Some aminotransferases, particularly kynurenine aminotransferases, can convert glyoxylate to glycine. Based on biochemical and structural characteristics, expression level, subcellular localization of some aminotransferases, a number of them appear able to catalyze the transamination of glyoxylate to glycine more efficiently than alanine glyoxylate aminotransferase-1. The aim of this minireview is to explore other undermining causes of primary hyperoxaluria and stimulate research toward achieving a comprehensive understanding of underlying mechanisms leading to the disease. Herein, we reviewed all aminotransferases in the liver for their functions in glyoxylate metabolism. Particularly, kynurenine aminotransferase-I and III were carefully discussed regarding their biochemical and structural characteristics, cellular localization, and enzyme inhibition. Kynurenine aminotransferase-III is, so far, the most efficient putative mitochondrial enzyme to transaminate glyoxylate to glycine in mammalian livers, might be an interesting enzyme to look over in hyperoxaluria etiology of primary hyperoxaluria and should be carefully investigated for its involvement in oxalate metabolism.
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PMID:Metabolism of Oxalate in Humans: A Potential Role Kynurenine Aminotransferase/Glutamine Transaminase/Cysteine Conjugate Beta-lyase Plays in Hyperoxaluria. 3090 3