Human erythrocyte prolidase and prolidase deficiency

Area of Science:

• Biochemistry
• Enzymology
• Human Genetics

Background:

• Prolidase deficiency is a rare genetic disorder characterized by clinical symptoms and defects in prolidase enzyme activity.
• The enzyme prolidase (EC 3.4.13.9) plays a crucial role in the hydrolysis of iminodipeptides.

Observation:

• A patient with prolidase deficiency excreted significant amounts of iminopeptides, including aspartyl-proline, glutamyl-proline, and glycyl-proline.
• Human prolidase was purified from erythrocytes, revealing a molecular weight of 55,000 per subunit.
• The enzyme exhibited specific cleavage rates for various iminodipeptides, with glycyl-L-proline being the most efficiently cleaved substrate.

Findings:

• The substrate specificity of human prolidase provides an explanation for the accumulation of urinary iminopeptides in prolidase deficiency.
• Erythrocyte transfusion as enzyme replacement therapy temporarily increased prolidase activity to 35% of normal levels, with a half-life of 41 days.
• Despite the increase in enzyme activity, urinary peptide-bound proline levels did not significantly change post-transfusion.

Implications:

• Understanding prolidase substrate specificity aids in diagnosing and managing prolidase deficiency.
• Enzyme replacement therapy using erythrocyte transfusion has limited efficacy and duration for prolidase deficiency.
• Further research is needed to explore more effective therapeutic strategies for prolidase deficiency.