title: Type II hyperprolinemia. Delta1-pyrroline-5-carboxylic acid dehydrogenase deficiency in cultured skin fibroblasts and circulating lymphocytes.
abstract: Type II hyperprolinemia is an inherited abnormality in amino acid metabolism characterized by elevated plasma proline concentrations, iminoglycinuria, and the urinary excretion of delta1-pyrroline compounds. To define the enzymologic defect of this biochemical disorder, we developed a specific, sensitive radioisotopic assay for the proline degradative enzyme delta1-pyrroline-5-carboxylic acid dehydrogenase. Using this assay, we have shown an absence of delta1-pyrroline-5-carboxylic acid dehydrogenase activity in the cultured fibroblasts from three patients with type II hyperprolinemia. We confirmed this result on cultured cells by demonstrating a similar absence of delta1-pyrroline-5-carboxylic acid dehydrogenase activity in extracts prepared from the peripheral leukocytes of these patients. Additionally, we found significantly decreased levels of delta1-pyrroline-5-carboxylic acid dehydrogenase activity in the leukocyte extracts from five obligate heterozygotes for type II hyperprolinemia. We also demonstrated a reduction in leukocyte delta1-pyrroline-5-carboxylic acid dehydrogenase activity in three successive generations of a family. These results prove that an absence of delta1-pyrroline-5-carboxylic acid dehydrogenase is the enzymologic defect in type II hyperprolinemia and that this defect is inherited in an autosomal recessive fashion.
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D002264:Carboxylic Acids; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D010375:Pedigree; D011392:Proline / Q000097:blood*; D011758:Pyrroles; D012867:Skin / Q000473:pathology*
chemical_list: D002264:Carboxylic Acids; D011758:Pyrroles; D011392:Proline; D010088:Oxidoreductases