Renin
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| Renin | |
|---|---|
 Molecular structure of renin | |
| Symbol(s): | REN |
| Other names: | Angiotensinogenase |
| Genetic data | |
| Locus: | Chr. 1 q32 |
| Protein Structure/Function | |
| Protein length: | 406 (Amino Acids) |
| Molecular Weight: | 45060 (Da) |
| Functions: | Converts angiotensinogen to angiotensin I |
| Motifs: | SP motif |
| Alternative Products: | 2 known isoforms produced from alternative splicing |
| Other | |
| Taxa expressing: | Homo sapiens; homologs many metazoan taxa |
| Subcellular localization: | Extracellular |
| Biophysicochemical properties: | KM=1 µmol/L for angiotensinogen |
| Database Links | |
| EC number: | 3.4.23.15 |
| Entrez: | 5972 |
| OMIM: | 179820 |
| RefSeq: | NM_000537 |
| UniProt: | P00797 |
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Renin (pronounced "Ree-nin" or "Rē-nin" (IPA: /ˈriːnɨn/)), also known as angiotensinogenase, is a circulating enzyme that participates in the renin-angiotensin system that mediates extracellular volume, arterial vasoconstriction, and consequently mean arterial blood pressure. The enzyme is secreted by the kidneys from specialized juxtaglomerular cells in response to decreases in glomerular filtration rate (a consequence of low blood volume), diminished filtered sodium chloride and sympathetic nervous system innervation. The enzyme circulates in the blood stream and hydrolyzes angiotensinogen secreted from the liver into the peptide angiotensin I. Angiotensin I is further cleaved in the lungs by endothelial bound angiotensin converting enzyme (ACE) into angiotensin II, the final active peptide. [1][2] The normal concentration in adult human plasma is 1.98-24.6 ng/L in the upright position. [3]
Structure
The primary structure of renin precursor consists of 406 amino acids with a pre and a pro segment carrying 20 and 46 amino acids respectively. Mature renin contains 340 amino acids and has a mass of 37 kD. [4]
Function
Renin activates the renin-angiotensin system by cleaving angiotensinogen, produced by the liver, to yield angiotensin I, which is further converted into angiotensin II by ACE, the angiotensin-converting enzyme primarily within the capillaries of the lungs. Angiotensin II then constricts blood vessels, increases the secretion of ADH and aldosterone, and stimulates the hypothalamus to activate the thirst reflex, each leading to an increase in blood pressure.
Renin is secreted from juxtaglomerular cells (of the afferent arterioles), which are activated via signaling (the release of prostaglandins) from the macula densa, which respond to the rate of fluid flow through the distal tubule, by decreases in renal perfusion pressure (through stretch receptors in the vascular wall), and by nervous stimulation, mainly through beta-1 receptor activation. A drop in the rate of flow past the macula densa implies a drop in renal filtration pressure. Renin's primary function is therefore to eventually cause an increase in blood pressure, leading to restoration of perfusion pressure in the kidneys.
Renin can bind to ATP6AP2, which results in a fourfold increase in the conversion of angiotensinogen to angiotensin I over that shown by soluble renin. In addition, renin binding results in phosphorylation of serine and tyrosine residues of ATP6AP2.[5]
Gene
The gene for renin, REN, spans 12 kb of DNA and contains 8 introns.[6] It produces several mRNA that encode different REN isoforms.
Secretion
Human Renin is secreted by at least 2 cellular pathways: a constitutive pathway for the secretion of prorenin and a regulated pathway for the secretion of mature renin [7].
Clinical implications
An over-active renin-angiotension system leads to vasoconstriction and retention of sodium and water. These effects lead to hypertension. Therefore, renin inhibitors can be used for the treatment of hypertension.
Aliskiren, is a first-in-class oral renin inhibitor, developed by Novartis in conjunction with the biotech company Speedel. It was approved by the US Food and Drug Administration in 2007. It is an octanamide, is the first known representative of a new class of completely non-peptide, low-molecular weight, orally active transition-state renin inhibitors. Designed through the use of molecular modeling techniques, it is a potent and specific in vitro inhibitor of human renin (IC50 in the low nanomolar range), with a plasma half-life of ≈24 hours. Tekturna has good water solubility and low lipophilicity and is resistant to biodegradation by peptidases in the intestine, blood circulation, and the liver. It was approved by the United States FDA on 6 March 2007, and for use in Europe on 27 August 2007. Its trade name is Tekturna in the USA, and Rasilez in the UK.
See also
References
- ↑ Fujino T, Nakagawa N, Yuhki K, Hara A, Yamada T, Takayama K, Kuriyama S, Hosoki Y, Takahata O, Taniguchi T, Fukuzawa J, Hasebe N, Kikuchi K, Narumiya S and Ushikubi F. (2004) Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP. J. Clin. Invest. 114:805-812. Full Text
- ↑ Brenner & Rector's The Kidney, 7th ed., Saunders, 2004. pp.2118-2119.Full Text with MDConsult subscription
- ↑ Hamilton Regional Laboratory Medicine Program - Laboratory Reference Centre Manual. Renin Direct
- ↑ Cloning and sequence analysis of cDNA for human renin precursor. ; PubMed Free text
- ↑ Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. 2002 Jun; PubMed Free text
- ↑ Human renin gene: structure and sequence analysis. 1984 Aug; PubMed Free text
- ↑ Different secretory pathways of renin from mouse cells transfected with the human renin gene. 1988 Mar 5; PubMed Free text (PDF - 1.3MB)
External links
Proteases: aspartic acid proteases (EC 3.4.23) | |
|---|---|
| Vertebrate | Pepsin · Chymosin · Renin · Signal peptide peptidase · Beta secretase |
| Pathogenic | Plasmepsin · HIV-1 protease |
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Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
