Renin precursors

For example, in certain instances the activation involved reduction in molecular weight whereas in other instances there was no appreciable molecular weight change. Since the activation process of a renin precursor potentially can have a profound effect on the plasma renin activity, we initiated studies on high-molecular-weight forms of renin. 

In the context of this scheme, big-big renin I with a higher specific activity than big-big renin II may very well be another intermediate product of activation. Although big-big renin II is only 1/2,000 as active as the small renin, it is possible that a completely inactive renin precursor exists. 

Cyclooxygenase (COX) activity is responsible for the formation of prostaglandins from their arachidonic acid precursor. Two COX isoforms have been identified, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues, COX-2 is typically only found after induction by proinflammatory stimuli. However, a constitutively expressed and highly regulated COX-2 is found in the kidney, both in the renal medulla and in the renal cortex. Renal cortical COX-2 is located in the area ofthe juxtaglomerular apparatus, and prostaglandins formed by COX-2 regulate the expression and secretion of renin in response to a reduction in NaCl concentration at the macula densa. 

An efficient route for the synthesis of the Phe-Phe hydroxyethy-lene dipeptide isostere precursors utilized for the design of potential inhibitors of renin and HIV-protease was developed. The key step is the zinc-mediated stereoselective allylation of A-protected a-amino aldehydes in aqueous solution (Eq. 8.32).70 NaBF4/M (M = Zn or Sn) showed facilitating allylation of a variety of carbonyl compounds in water, and a-and y-addition products of crotylations could be alternatively obtained under the control of this novel mediator (Eq. 8.33).71... 

This multistep process is initiated by the enzyme renin. Angiotensinogen is a precursor peptide molecule released into the circulation from the liver. 

Renin [2] is an aspartate proteinase (see p. 176). It is formed by the kidneys as a precursor (prorenin), which is proteolytically activated into renin and released into the blood. In the blood plasma, renin acts on angiotensinogen, a plasma glycoprotein in... 

Natriuretic peptides are naturally occurring substances in the body that oppose the activity of the renin-angiotensin system. The natriuretic peptide family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). All three natriuretic peptides are synthesized from cleavage of a larger precursor polypeptide. In the ventricles and brain, the synthesis of BNP predominates ANP is synthesized by cardiac myocytes predominately in the atria and CNP is synthesized in the brain, blood vessels, and kidney. 

For many years, prorenin was considered to be an inactive precursor of renin, with no function of its own. Thus the observation noted above in the section on renin that prorenin circulates at high levels was surprising. Recently, however, a receptor that specifically binds prorenin has been identified. Since it also binds active renin, the receptor is referred to as the "(pro)renin" receptor. 

Angiotensinogen, which is secreted by the liver and circulates in the blood, is converted to the physiologically inactive decapeptide angiotensin I by cleavage of a Leu-Leu peptide bond by the 328-residue renin.d f Its precursor preprorenin is produced in the kidneys by the juxtaglomerular cells as well as in some other tissues and undergoes several... 

The ANF hormones, which derive from higher-molecular-weigth precursors (atriopeptigens), have diuretic properties, i.e. an administration of ANF in the rat increases diuresis and natriuresis (the release of Arg-vasopressin is inhibited) and at the same time the vessels are dilated, apparently by inhibition of catecholamines and angiotensin II. In addition, it has been shown that under volume loading the ANF peptides are released from the atria and develop their effects as hormones in renal, vascular, and other tissues. They can be considered as functional antagonists of the renin-angiotensin system. 

The renin-angiotensin system (RAS) controls blood pressure, blood volume and electrolytic balance. Two main enzymes influence the release of angiotensin II from its endogenous precursor, angiotensinogen renin and angiotensin-converting enzyme (ACE) (Fig. 6.1). 

The peptides are normally formed from a precursor molecule - angiotensinogen - an a2-globulin in the blood, by the action of a 340 amino acid glycoprotein called renin, which acts as an aspartyl protease enzyme (see renin inhibitors). Renin, and its precursor protein, are both stored in the juxtaglomerular cells of the kidney, and release is controlled by three different pathways within the kidney sensitive to Na -transport, blood vessel stretch and Pi-adrenoceptor activation, respectively. Overall, activation of the renin-angiotensin systems is hypertensive, but serves to increase renal perfusion. 

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