Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The activity of alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44) has been measured in the unfractionated livers of 20 patients with primary hyperoxaluria type 1 (PH1), three patients with other forms of primary hyperoxaluria and one PH1 heterozygote. The subcellular distribution of AGT activity was examined in four of the PH1 livers and in the liver of the PH1 heterozygote. 2. The mean AGT activity in the unfractionated PH1 livers was 12.6% of the mean control value. The activities of other aminotransferases and the peroxisomal marker enzymes were normal. When corrected for cross-over from glutamate:glyoxylate aminotransferase (GGT; EC 2.6.1.4), the mean AGT activity in the PH1 livers was reduced to 3.3% of the control values. 3. The livers from a patient with primary hyperoxaluria type 2 (D-glycerate dehydrogenase deficiency) and one with an undefined form of primary hyperoxaluria (possibly oxalate hyperabsorption) had normal AGT levels. The livers of a very mild PH1-type variant and a PH1 heterozygote had intermediate levels of AGT activity. 4. Subcellular fractionation of four PH1 livers by sucrose gradient isopycnic centrifugation demonstrated a complete absence of peroxisomal AGT activity. The subcellular distribution of the residual AGT activity was very similar to that of GGT activity (i.e. mainly cytosolic with a small amount mitochondrial). There were no alterations in the subcellular distributions of any of the peroxisomal marker enzymes. The subcellular distribution of AGT activity in the PH1 heterozygote liver was similar to that of the control (i.e. mainly peroxisomal).
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PMID:Further studies on the activity and subcellular distribution of alanine:glyoxylate aminotransferase in the livers of patients with primary hyperoxaluria type 1. 341 63

Urolithiasis is uncommon in adolescence and rare in early childhood. In pediatric populations, congenital urinary tract anomalies associated with stasis and infection, idiopathic urolithiasis (adolescents), and nephrocalcinosis (premature infants) account for the majority of urolithiasis patients. Inborn errors of metabolism, such as the primary hyperoxalurias, are rare causes of urolithiasis in childhood. We report six children (mean age at symptom onset 1.3 years; range 0.32-4.1 years) with moderate hyperoxaluria (mean 1.10 +/- 0.58 mmoL/1.73m2 per day; range 0.69-2.19 mmoL/1.73m2 per day). Urolithiasis was present in four. Stones from two children were comprised of calcium oxalate dihydrate. Calcium oxalate crystalluria was seen in two of the patients. Findings included a mean urine calcium concentration of 6.61 +/- 2.28 mg/kg per day, urine citrate of 925.5 +/- 291.29 mg/g of creatinine per day, and mean renal clearance of 99.83 +/- 23.27 mL/min. All children were born full term, none was receiving diuretics, and none had recurrent urinary tract infections. Secondary causes of hyperoxaluria, including dietary oxalate excess, pyridoxine deficiency, and malabsorption, were excluded. Urine glycolate and glycerate were normal in all patients. In one hyperoxaluric member of each sibship, hepatic alanine-glyoxylate aminotransferase and D-glycerate dehydrogenase/glyoxylate reductase activity were normal. The clinical and biochemical features of these children are unlike those in previously recognized hyperoxaluric states. Thus, our description of a separate hyperoxaluric entity, referred to as unclassified hyperoxaluria.
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PMID:Hyperoxaluria and urolithiasis in young children: an atypical presentation. 1060 14

Failure to detoxify the intermediary metabolite glyoxylate in human hepatocytes underlies the metabolic pathology of two potentially lethal hereditary calcium oxalate kidney stone diseases, PH (primary hyperoxaluria) types 1 and 2. In order to define more clearly the roles of enzymes involved in the metabolism of glyoxylate, we have established singly, doubly and triply transformed CHO (Chinese-hamster ovary) cell lines, expressing all combinations of normal human AGT (alanine:glyoxylate aminotransferase; the enzyme deficient in PH1), GR/HPR (glyoxylate/hydroxypyruvate reductase; the enzyme deficient in PH2), and GO (glycolate oxidase). We have embarked on the preliminary metabolic analysis of these transformants by studying the indirect toxicity of glycolate as a simple measure of the net intracellular production of glyoxylate. Our results show that glycolate is toxic only to those cells expressing GO and that this toxicity is diminished when AGT and/or GR/HPR are expressed in addition to GO. This finding indicates that we have been able to reconstruct the glycolate-->glyoxylate, glyoxylate-->glycine, and glyoxylate-->glycolate metabolic pathways, catalysed by GO, AGT, and GR/HPR respectively, in cells that do not normally express them. These results are compatible with the findings in PH1 and PH2, in which AGT and GR/HPR deficiencies lead to increased oxalate synthesis, due to the failure to detoxify its immediate precursor glyoxylate. These CHO cell transformants have a potential use as a cell-based bioassay for screening small molecules that stabilize AGT or GR/HPR and might have use in the treatment of PH1 or PH2.
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PMID:Reconstruction of human hepatocyte glyoxylate metabolic pathways in stably transformed Chinese-hamster ovary cells. 1630 82

In the present paper we report the oral findings of a patient who was diagnosed with hyperoxaluria. Hyperoxalurias can basically be classified as primary and secondary, with the first being inborn errors of metabolism and the second a result of excessive oxalate intake. Primary hyperoxalurias form a rare group of metabolic diseases that are inherited in the autosomal recessive fashion. The affected genes code for specific hepatic enzymes that are involved in glyoxylate metabolism and their deficiency results in overproduction of oxalate. Two different types are described: Primary hyperoxaluria type I results from a deficiency of peroxisomal enzyme alanine-glyoxylate aminotransferase and the more rare type II from a deficiency of cytosolic enzyme D-glycerate dehydrogenase. Since oxalate is primarily excreted through the kidneys, abnormally high concentration of oxalate in the urine occurs. This can in turn result in recurrent kidney stones and parenchymal renal damage and end-stage renal disease (ESRD). Inability to further excrete oxalate through the kidneys leads to its deposition in various organs (oxalosis). Several oral findings have been described in patients with oxalosis, most important of whose are bone resorption in the jaws, external root resorption and rapidly progressive dental mobility, as well as dental pain associated with deposition of oxalate in the dentine and the pulp.
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PMID:Oral findings associated with primary hyperoxaluria type I. 2241 69