Differences in the kinetic rate constants of normal and high molecular weight renin substrate from term pregnancy human plasma.

Shionoiri, Hiroshi; Gotoh, Eiji; Kaneko, Yoshihiro; Eggena, Peter; Sambhi, Mohinder P.

doi:10.1507/endocrj1954.30.731

Cited by 7 publications

(2 citation statements)

References 22 publications

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“…Conflicting evidence on the effect of oestrogens on the Km has been obtained with non-autologous assays. Reduced (McDonald, Cohen, Lucas & Conn, 1977), unchanged (Gould, DeWolf, Goodman et al 1980), or even increased (Shionoiri, Gotoh, Kaneko et al 1983) affinity of the renin-angiotensinogen reaction has been reported.…”

Section: Resultsmentioning

confidence: 99%

The renin-angiotensinogen reaction during pregnancy and oral contraception: estimation of kinetic parameters by an autologous plasma renin assay

Daniels¹,

Eisen²,

Slater³

1987

Journal of Endocrinology

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A method has been developed which allows estimation of the kinetic parameters of the plasma renin-angiotensinogen reaction from data obtained by autologous renin assays at several plasma dilutions. The quantitative aspects of the renin-angiotensin system were examined in 28 plasma samples from 23 healthy, normotensive pregnant women. They were compared with 20 women who were not pregnant, of whom 12 were taking oral contraceptives and eight were not. In the first 3 months of pregnancy, there was a sharp increase in plasma renin activity and concentration. Plasma angiotensinogen rose steadily throughout pregnancy. The higher concentrations of renin and angiotensinogen would lead to an increase in angiotensin formation with potentially adverse consequences. However, this increase may be reduced by the fall in the affinity between renin and angiotensinogen which is suggested by the present observation that the Michaelis-Menten constant (Km) attained values five to six times higher than those seen in women not taking oral contraceptives. The smaller increases in plasma renin and angiotensinogen induced by oral contraceptives were less effectively compensated by lower affinity. Circumstantial evidence is provided which suggests that the observed high Km values may be due to oestrogen/pregnancy-induced synthesis of an angiotensinogen with a lower affinity for renin.

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Section: Resultsmentioning

confidence: 99%

The renin-angiotensinogen reaction during pregnancy and oral contraception: estimation of kinetic parameters by an autologous plasma renin assay

Daniels¹,

Eisen²,

Slater³

1987

Journal of Endocrinology

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show abstract

“…The second area of contention concerns the ability of AGT polymers to act as a substrate for renin. Early work on HMrA isolated from plasma concludes that it is recognized by renin [22,23]. However, later work with purified recombinant protein suggests that AGT aggregates are not recognized by renin, possibly due to the presence of intermolecular disulfide bridges [21].…”

Section: Introductionmentioning

confidence: 99%

Polymerization of human angiotensinogen: insights into its structural mechanism and functional significance

Stanley

Serpell

Stein

2006

Biochemical Journal

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In the present study, we have investigated the in vitro polymerization of human plasma AGT (angiotensinogen), a non-inhibitory member of the serpin (SERine Protease INhibitor) family. Polymerization of AGT is thought to contribute to a high molecular mass form of the protein in plasma that is increased in pregnancy and pregnancy-associated hypertension. The results of the present study demonstrate that the polymerization of AGT occurs through a novel mechanism which is primarily dependent on non-covalent linkages, while additional disulfide linkages formed after prolonged incubation are not essential for either formation or stability of polymers. We present the first analyses of AGT polymers by electron microscopy, CD spectroscopy, stability assays and sensitivity to proteinases and we conclude that their structure differs from the 'loop-sheet' polymers typical of inhibitory serpins. Histidine residues within the unique N-terminal extension of AGT appear to influence polymer formation, although polymer formation can still take place after their removal by renin. At a functional level, we show that AGT polymers are not substrates for renin, so polymerization of AGT in plasma would predictably lead to decreased formation of AngI (angiotensin I) with blood pressure lowering. Polymerization may therefore be an appropriate response to hypertension. The ability of AGT to protect its renin cleavage site through polymerization may explain why the AngI decapeptide has remained linked to the large and apparently inactive serpin body throughout evolution.

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Reduced Activation and Affinity of Renin during Pregnancy and Oral Contraception: Determination of Kinetic Parameters by a Fully Autologous Plasma Renin Assay

Cr¹,

Eisen²,

Slater³

1986

Kinins IV

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Differences in the kinetic rate constants of normal and high molecular weight renin substrate from term pregnancy human plasma.

Abstract: We have previously reported

Cited by 7 publications

References 22 publications

The renin-angiotensinogen reaction during pregnancy and oral contraception: estimation of kinetic parameters by an autologous plasma renin assay

The renin-angiotensinogen reaction during pregnancy and oral contraception: estimation of kinetic parameters by an autologous plasma renin assay

Polymerization of human angiotensinogen: insights into its structural mechanism and functional significance

Reduced Activation and Affinity of Renin during Pregnancy and Oral Contraception: Determination of Kinetic Parameters by a Fully Autologous Plasma Renin Assay

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