prorenin

Prorenin is the inactive precursor of the enzyme renin, a protease that initiates the renin-angiotensin system by cleaving angiotensinogen to angiotensin I. Prorenin is produced mainly by juxtaglomerular cells of the kidney and is secreted into the circulation together with renin. The prorenin pool provides a reservoir that can be activated to renin as needed, and prorenin is also produced locally in various tissues, including the placenta.

Biogenesis and activation: Prorenin is synthesized as a larger zymogen with an N-terminal prosegment that inhibits the active site. In the secretory pathway, proteolytic removal of the prosegment yields active renin; nevertheless, a portion of prorenin is released in its pro-form. In some circumstances, prorenin can be activated non-proteolytically upon binding to receptors or within specific cellular environments, increasing local renin activity without peptide cleavage. The circulating prorenin/renin ratio varies with age, hormonal state, and disease.

Prorenin receptor interactions: The prorenin receptor (PRR) binds prorenin with high affinity and can induce a conformational change that increases catalytic efficiency and also activates intracellular signaling pathways, such as MAP kinases, independently of angiotensin II. This signaling can contribute to tissue remodeling and fibrosis in experimental models.

Clinical relevance: Circulating prorenin levels are sometimes measured to assess renin-angiotensin system status in research and certain clinical contexts. Prorenin concentrations vary with age, hormonal state, and disease. Placental prorenin is a major contributor to circulating prorenin during pregnancy. Elevated prorenin has been reported in diabetes and chronic kidney disease, though its exact diagnostic value remains an area of study.