Biochemical studies on Lowe's syndrome.
Lowe's syndrome (oculo-cerebro-renal syndrome) has been studied biochemically. The disease was characterized by proteinuria, sialic aciduria and the excretion of undersulfated chondroitin sulfate A due mainly to malfunction of renal tubules. However, cultured skin fibroblasts from patients were found also to produce markedly undersulfated glycosaminoglycans. The undersulfation was caused by depressed sulfation rather than by increased desulfation. Subsequent studies have revealed that degradation of active sulfate (adenosine 3'-phosphate 5'-phosphosulfate, PAPS) was markedly elevated in the cells from patients whereas PAPS biosynthesis or sulfate transfer of sulfate from PAPS to glycosaminoglycan acceptors were normal. The enzyme involved in PAPS degradation was then identified as a nucleotide pyrophosphatase which is capable of degrading various nucleotides. The level of the enzyme activity in patients' cells was about ten times higher than that in normal cells and the level in heterozygotes were intermediate between patients and normal individuals. It was suggested that Lowe's syndrome is caused by elevation of biosynthesis of a nucleotide pyrophosphatase having a capacity to degrade PAPS due to a defect in regulating the enzyme synthesis.
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007223:Infant; D008297:Male; D009800:Oculocerebrorenal Syndrome / Q000378:metabolism*; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism; D011507:Proteinuria / Q000378:metabolism; D011755:Pyrophosphatases / Q000378:metabolism; D015499:Renal Tubular Transport, Inborn Errors / Q000378:metabolism*; D012794:Sialic Acids / Q000652:urine; D012867:Skin / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism
D006025:Glycosaminoglycans; D012794:Sialic Acids; D013431:Sulfates; D010724:Phosphoadenosine Phosphosulfate; D011755:Pyrophosphatases; C021899:nucleotide pyrophosphatase