Valle D, Goodman S I, Applegarth D A, Shih V E, Phang J M
J Clin Invest. 1976 Sep;58(3):598-603. doi: 10.1172/JCI108506.
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.
II型高脯氨酸血症是一种氨基酸代谢的遗传性异常，其特征为血浆脯氨酸浓度升高、亚氨基甘氨酸尿症以及δ1-吡咯啉化合物的尿排泄。为了确定这种生化紊乱的酶学缺陷，我们开发了一种针对脯氨酸降解酶δ1-吡咯啉-5-羧酸脱氢酶的特异性、灵敏的放射性同位素测定法。使用该测定法，我们发现三名II型高脯氨酸血症患者的培养成纤维细胞中缺乏δ1-吡咯啉-5-羧酸脱氢酶活性。我们通过证明这些患者外周血白细胞提取物中同样缺乏δ1-吡咯啉-5-羧酸脱氢酶活性，在培养细胞上证实了这一结果。此外，我们发现五名II型高脯氨酸血症的 obligate 杂合子的白细胞提取物中δ1-吡咯啉-5-羧酸脱氢酶活性显著降低。我们还在一个家族的连续三代中证明了白细胞δ1-吡咯啉-5-羧酸脱氢酶活性降低。这些结果证明，缺乏δ1-吡咯啉-5-羧酸脱氢酶是II型高脯氨酸血症的酶学缺陷，并且这种缺陷以常染色体隐性方式遗传。
