THE ENZYMATIC DEFECT IN TYPE II HYPERPROLINEMIA: ABSENCE OF Δ-PYRROLINE-5-CARBOXYLIC ACID DEHYDROGENASE ACTIVITY

Abstract

Type II hyperprolinemia is characterized by hyperprolinemia, iminoglycinuria and urinary excretion of o-aminobenzaldehyde (OAB) reactive material, presumably Δ1-pyrroline-5-carboxylic acid (PCA). We now report the first demonstration of the enzymatic defect responsible for this syndrome. The patient is an eleven year old female with 15x elevated plasma proline values, iminoglycinuria, and OAB reactive material in her urine. We compared the enzymes of proline metabolism in the fibroblasts of the patient with those in 3 normal fibroblast lines. All cells were grown in Eagles' MEM. PCA dehydrogenase was measured by recovering product glutamate-14C formed from precursor PCA-14C (7.2 × 10−6M). The reaction mixture also included NAD (3.7 × 10−4%) and 10-50 μgrams of fibroblast protein. Sonicates of the patient's fibroblasts had no detectable PCA dehydrogenase activity while sonicates from control fibroblast lines produced 34 ± 2 n moles/hour/mg protein. This value represents a 10x increase over the reaction blank. The activities of ornithine-δ-transaminase and PCA reductase were normal in sonicates of the patient's cells. These results demonstrate that the enzymatic defect in Type II hyperprolinemia is an absent or defective PCA dehydrogenase. This block in the proline catabolic pathway results in accumulation of PCA which is excreted or converted to proline by PCA reductase.