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Original Article

Kinetic Analysis of the Reaction of Human Renin with Human High and Low Molecular Weight Angiotensinogen

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Pages 327-338 | Published online: 07 Jul 2009
 

Abstract

Objective: In addition to the usual predominant form of plasma angioten-sinogen (low molecular weight angiotensinogen) (LMrA) that has been well characterized, a high molecular weight form of angiotensinogen (HMrA) occurs in appreciable quantities in plasma of pregnant women and is the predominant form of angiotensinogen in the placenta and amniotic fluid. One half of women who have pregnancy-induced hypertension exhibit significantly elevated plasma HMrA levels. The present study is designed to determine if HMrA is a good substrate for human renin.

Methods: The pH profile, a Km to V for the reaction of human renin with LMrA and HMrA. was determined.

Results: The pH profiles for HMrA and LMrA were distinctly different. The experimentally determined kinetic parameters show that at pH 5.9, renin would hydrolyze both substrates at equal rates in an equimolar mixture of the two substrates at any concentration of substrate. At pH 7.3 LMrA would be consumed 1.9 times faster than HMrA.

Conclusions: HMrA is a good substrate for human renin. HMrA should be considered a significant component of the renin-angiotensin system at those sites where it occurs in an appreciable concentration. Since the concentration of LMrA in plasma is slightly lower than the Km for the reaction of human rennin with LMrA, the concentration of LMrA is a rate-limiting factor in the production of angiotensin I and angiotensin II.

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