کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1904919 1534680 2012 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Primary hyperoxalurias: Disorders of glyoxylate detoxification
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Primary hyperoxalurias: Disorders of glyoxylate detoxification
چکیده انگلیسی

Glyoxylate detoxification is an important function of human peroxisomes. Glyoxylate is a highly reactive molecule, generated in the intermediary metabolism of glycine, hydroxyproline and glycolate mainly. Glyoxylate accumulation in the cytosol is readily transformed by lactate dehydrogenase into oxalate, a dicarboxylic acid that cannot be metabolized by mammals and forms tissue-damaging calcium oxalate crystals. Alanine-glyoxylate aminotransferase, a peroxisomal enzyme in humans, converts glyoxylate into glycine, playing a central role in glyoxylate detoxification. Cytosolic and mitochondrial glyoxylate reductase also contributes to limit oxalate production from glyoxylate. Mitochondrial hydroxyoxoglutarate aldolase is an important enzyme of hydroxyproline metabolism. Genetic defect of any of these enzymes of glyoxylate metabolism results in primary hyperoxalurias, severe human diseases in which toxic levels of oxalate are produced by the liver, resulting in progressive renal damage. Significant advances in the pathophysiology of primary hyperoxalurias have led to better diagnosis and treatment of these patients, but current treatment relies mainly on organ transplantation. It is reasonable to expect that recent advances in the understanding of the molecular mechanisms of disease will result into better targeted therapeutic options in the future. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of peroxisomes in Health and Disease.


► Errors of glyoxylate detoxification result in primary hyperoxalurias.
► Molecular genetics of primary hyperoxalurias are reviewed.
► Main clinical aspects of primary hyperoxalurias are summarized.
► Prospects for molecular therapies are discussed.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1822, Issue 9, September 2012, Pages 1453–1464
نویسندگان
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