Prolidase deficiency

Prolidase Deficiency (PD) is a rare autosomal recessive disease associated to elevated plasma and urine imidodipeptides and characterized by defective wound healing, untractable skin lesions, various degree of mental retardation and recurrent infections. Bone and joint abnormalities were referred occasionally and included the signs and symptoms of prolidase deficiency, but were not deeply investigated in PD patients, due to the more devastating effect of the other peculiar PD outcomes.


PD is caused by mutation in PEPD gene encoding for prolidase, a cytosolic manganese dependent exopeptidase, the only enzyme in vertebrates able to hydrolyze the tertiary amide bond present in iminodipeptides containing proline or hydroxyproline at their C-terminal end. Thus prolidase is involved in the very last stage of the catabolism of endogenous as well as dairy proteins, especially of those proteins particularly rich in iminopeptides, such as collagens. It has an important role in proline recycling both for proteins synthesis and cellular growth and prolidase activity was reported to affect both type I collagen synthesis and degradation. Since collagen I is the main component of the bone organic extracellular matrix a role of prolidase in skeletal development could be expected.