hydroxylysine and Metabolism--Inborn-Errors

Topics: Amino Acid Sequence; Amino Acids; Aminopropionitrile; Animals; Chemical Phenomena; Chemistry; Collagen; Copper; Desmosine; Elastin; Humans; Hydroxylysine; Lysine; Metabolism, Inborn Errors; Nutrition Disorders; Nutritional Physiological Phenomena; Penicillamine; Protein-Lysine 6-Oxidase; Tropocollagen

An abnormal ninhydrin positive compound was observed in the urine of two unrelated patients with neurological abnormalities. The compound was isolated by cation exchange followed by preparative paper chromatography and finally purified via cation exchange column chromatography. Its identification as O-phosphohydroxylysine resulted from FAB mass spectrometry and NMR spectroscopy. Chemical synthesis confirmed the structure. It was tentatively postulated that these patients had a defect of the metabolism of hydroxylysine, viz., a deficiency of the enzyme O-phosphohydroxylysine phospholyase.

Topics: Adolescent; Child; Chromatography, Thin Layer; Electrophoresis; Female; Humans; Hydrolysis; Hydroxylysine; Magnetic Resonance Spectroscopy; Male; Metabolism, Inborn Errors

A patient with protein-losing gastroenteropathy and egg allergy has been shown to have a previously unrecognized organic aciduria, D-2-hydroxyglutaric aciduria. The observations made are consistent with an inherited metabolic disorder in the catabolism of 5-aminolaevulinate possibly due to deficient activity of a specific D-2-hydroxyglutarate dehydrogenase.

Topics: Aminolevulinic Acid; Asthma; Child, Preschool; Chromatography, Gas; Chromatography, Ion Exchange; Food Hypersensitivity; Glutarates; Humans; Hydroxylysine; Male; Metabolism, Inborn Errors; Protein-Losing Enteropathies; Syndrome

Cell culture studies were performed on members of a family in which two sisters, ages 9 and 12, have a similar disorder characterized clinically by severe scoliosis, joint laxity and recurrent dislocations, hyperextensible skin, and thin scars. The skin collagen from the sisters was markedly deficient in hydroxylysine, but other amino acids were present in normal amounts. Hydroxylysine in collagen from fascia and bone was reduced to a lesser extent. Since the most likely explanation for the hydroxylysine deficiency was a reduction in enzymatic hydroxylation of lysine residues in protocollagen, we measured the activity of lysyl-protocollagen hydroxylase in crude lysates of cultured skin fibroblasts. Enzyme activities in the two affected children were 14 and 10% of controls, whereas the activity was about 60% of normal in the mother, a pattern most consistent with autosomal recessive inheritance. The mutant enzyme demonstrated the same cofactor requirements as that from normal cells. Deficiency of lysyl-protocollagen hydroxylase is the first inborn error of human collagen metabolism to be defined at the biochemical level.

Topics: Adolescent; Adult; Amino Acids; Cells, Cultured; Child; Collagen; Consanguinity; Ehlers-Danlos Syndrome; Female; Fibroblasts; Humans; Hydrogen-Ion Concentration; Hydroxylysine; L-Lactate Dehydrogenase; Lysine; Male; Metabolism, Inborn Errors; Methyltransferases; Mixed Function Oxygenases; Procollagen-Proline Dioxygenase; Proline; Protein Precursors; Serine; Skin; Time Factors

Topics: Amino Acids; Child, Preschool; Chromatography, Paper; Collagen; Diet Therapy; Female; Humans; Hydroxylysine; Hydroxyproline; Kidney; Lysine; Metabolism, Inborn Errors; Stereoisomerism