RENNIN

Description

Renin is the rate-limiting enzyme for the initiation of the cascade of the renin-angiotensin system. Plasma renin activity is a marker for hypertension. This is a drug target for hypertension and renal disease. In the late 18th century, renin was discovered based on the observation that the injection of saline extracts from fresh rabbit kidneys into other rabbits increased arterial blood pressure.

The Uses of RENNIN

Rennin is a milk coagulant that is an enzyme obtained from the abo- masum portion of the stomach of suckling mammals. it is most active at ph 3.8. one part purified rennin will coagulate more than five million parts of milk. the commercial extract of rennin is termed rennet. it is used to coagulate milk in making cheese, junket, and custard. see rennet.

Definition

An enzyme secreted by cellslining the stomach in mammals thatis responsible for clotting milk. Itacts on a soluble milk protein (caseinogen),which it converts to theinsoluble form casein. This ensuresthat milk remains in the stomachlong enough to be acted on by protein-digesting enzymes.

Biological Functions

Renin is an enzyme that is synthesized and stored in the renal juxtaglomerular apparatus and that catalyzes the formation of a decapeptide, angiotensin I, from a plasma protein substrate. Renin has a narrow substrate specificity that is limited to a single peptide bond in angiotensinogen, a precursor of angiotensin I. Renin is considered to control the rate-limiting step in the ultimate production of angiotensin II. Control of renin secretion by the juxtaglomerular apparatus is important in determining the plasma renin concentration.
Three generally accepted mechanisms are involved in the regulation of renin secretion. The first depends on renal afferent arterioles that act as stretch receptors or baroreceptors. Increased intravascular pressure and increased volume in the afferent arteriole inhibits the release of renin. The second mechanism is the result of changes in the amount of filtered sodium that reaches the macula densa of the distal tubule. Plasma renin activity correlates inversely with dietary sodium intake. The third renin secretory control mechanism is neurogenic and involves the dense sympathetic innervation of the juxtaglomerular cells in the afferent arteriole; renin release is increased following activation of 1-adrenoceptors by the neurotransmitter norepinephrine.
Angiotensin II, the primary end product of the renin–angiotensin system, acts on the juxtaglomerular cells to inhibit the release of renin; this process is therefore a negative feedback mechanism. The half-life of renin in the circulation is 10 to 30 minutes, with inactivation occurring primarily in the liver. Small amounts of renin are eliminated by the kidneys. Pure human renin has been used to develop specific inhibitors of the enzyme. Low-molecular-weight orally effective renin inhibitors are under development.

Clinical Use

Renin inhibitors can be used for the treatment of hypertension. In current medical practice, PRA is the indicator of RAS overactivity and is more commonly treated using either ACE blockers and/or AT1 blockers rather than a direct oral renin inhibitor. ACE inhibitors and/or AT1 blockers are also part of the standard treatment after a heart attack. The diagnosis of kidney cancer includes a juxtaglomerular cell tumor (reninoma), Wilms’ tumor, and renal cell carcinoma, all of which may produce renin and lead to hypertension in patients.

Structure and conformation

Renin is a highly specific endopeptidase whose only known function is to generate angiotensin I (Ang I) from angiotensinogen (AGT), initiating a cascade of reactions that produces elevated blood pressure and increased sodium retention by the kidney. REN1 is a protein coding gene with 406 aa residues in humans; it forms an aspartyl protease.