Abstract
Summary: Biochemical studies on human prolidase (EC 3.4.13.9) and prolidase deficiency are described. The urine sample from a 32-year-old female with prolidase deficiency was examined. Diagnosis was based on clinical features and defects of prolidase in her erythrocytes. She excreted massive amounts of iminopeptides, where three major peptides were identified; aspartyl-proline, glutamyl-proline and glycyl-proline. The prolidase was purified approximately 10,000-fold from the normal human erythrocytes through an eight step procedure. The purified enzyme consisted of two identical subunits of which the molecular weight was calculated to be 55,000. The relative cleavage rates of the enzyme for glycyl-L-proline, L-alanyl-L-proline, L-leucyl-L-proline, L-prolyl-L-proline, and glycyl-hydroxy-L-proline were 100%, 53%, 27%, 31% and 2%, respectively. The relative substrate specificity of the enzyme offers a reasonable explanation for the presence of a higher level of urinary imidodipeptides in a patient with prolidase deficiency. An attempt at erythrocyte transfusion was performed, aimed at enzyme replacement therapy. After the transfusion (erythrocytes from 800 ml of whole blood), the prolidase activity of the peripheral erythrocyte was elevated to approximately 35% of the normal values and gradually decresed (half-life, 41 days). During this period urinary peptide-bound proline was monitored, but no significant change was observed.
Speculation: The prolidase activity of transfused erythrocytes is relatively stable; however, intracellular enzyme activity has no effect on net proline loss and skin lesions. Enzyme replacement may be a possible attempt at therapy of the disease, but other forms of replacement should be tried.
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Endo, F., Matsuda, I., Ogata, A. et al. Human Erythrocyte Prolidase and Prolidase Deficiency. Pediatr Res 16, 227–231 (1982). https://doi.org/10.1203/00006450-198203000-00013
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DOI: https://doi.org/10.1203/00006450-198203000-00013
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