Glutamyl ribose 5-phosphate storage disease. A hereditary defect in the degradation of poly(ADP-ribosylated) proteins.
A patient with a lysosomal storage disease, progressive neurologic degeneration, and renal failure was found to have accumulated a low molecular weight ninhydrin and phenol-H2SO4 reactive compound. Amino acid analysis and gas chromatography-mass spectrometry identified a glutamic acid moiety. Direct insertion mass spectrometry proved the carbohydrate portion to be a sugar phosphate. NaB3H4 reduction and borate electrophoresis, paper chromatography, and enzymatic digestion indicated the presence of ribose 5-phosphate. Quantitative analysis of the intact compound indicated a 1:1:1 ratio for glutamic acid: ribose:phosphate. Brain was found to contain 0.96 mumol/g, wet weight, and kidney 0.60 mumol/g, wet weight, of glutamyl ribose 5-phosphate. This substance is the linkage region in ADP-ribosylation of histones and other proteins. It is suggested that the primary defect in this patient is a genetic abnormality of ADP-ribose protein hydrolase (Okayama, H., Honda, M., and Hayaishi, O. (1978) Proc. Natl. Acad. Sci. U. S .A. 75, 2254-2257).
D000596:Amino Acids / Q000032:analysis; D001894:Borohydrides; D001923:Brain Chemistry; D019757:Carbon-Oxygen Lyases; D002648:Child; D002854:Chromatography, Paper; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007668:Kidney / Q000032:analysis; D008190:Lyases / Q000172:deficiency*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000378:metabolism*; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D010428:Pentosephosphates / Q000378:metabolism*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D012267:Ribosemonophosphates / Q000378:metabolism*
D000596:Amino Acids; D001894:Borohydrides; D009702:Nucleoside Diphosphate Sugars; D010428:Pentosephosphates; D012267:Ribosemonophosphates; D011064:Poly Adenosine Diphosphate Ribose; C025364:sodium borohydride; C040262:glutamyl ribose 5-phosphate; D008190:Lyases; D019757:Carbon-Oxygen Lyases; C019621:ADP-ribose-histone hydrolase