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Renin

Renin, also known as angiotensinogenase, is an aspartyl protease and belongs to the protein family peptidase A1. Aspartyl proteases are endopeptidases that typically use two aspartate residues in the active site in a reduction-oxidation reaction with water to specifically cleave peptide substrates. Mature renin circulates in the blood and contains 406 amino acid residues and has a mass of approximately 37 kDa. The function of renin is to cleave the angiotensin I precursor, angiotensinogen, to produce angiotensin I.

Renin is secreted by the kidneys. The kidneys act both directly and indirectly to regulate arterial blood pressure and provide the major long term mechanism of blood pressure and control. The direct mechanism changes blood volume independently of hormones. When blood pressure and blood volume increase the kidneys can not filter all of the liquids and thus liquids are lost in the urine to decrease blood pressure and blood volume.

The indirect mechanism, or the renin-angiotensin system (RAS), controls blood volume and blood pressure through renin and two forms of angiotensin. Renin is involved in the first step of a cascade that eventually produces angiotensin II. The specialized granular cells of the juxtaglomerular apparatus secrete renin when stimulated by the macula densa when blood pressure or blood volume decreases. Renin circulating in the blood stream cleaves a small 10 residue portion of plasma protein angiotensinogen that is secreted by the liver. Cleavage of angiotensinogen produces the inactive precursor angiotensin I that is converted to angiotensin II by angiotensin-converting enzyme primarily in the lungs. Angiotensin II increases blood pressure in three ways.

• Angiotensin II constricts blood vessels by influencing smooth muscle tissue. The heart pumps faster to overcome the constricted arteries and blood pressure rises.
• Angiotensin II stimulates the adrenal cortex to secrete aldosterone that causes renal adsorption of sodium. when sodium moves into the blood stream water follows to increase the blood volume.
• Angiotensin II causes the posterior pituitary gland to release vasopressin, also known as antidiuretic hormone, to induce water reabsorption.

Additionally, angiotensin II triggers the sensation of thirst.

The release of renin into the blood stream ultimately raises blood pressure. The kidneys restore and maintain blood pressure homeostasis by regulating blood volume through the action of renin. Although blood volume varies with age, body size, and sex, renal mechanisms usually maintain it to 5 liters.

Renin has been identified in many eukaryotic organisms including; humans, mice, marmosets, monkeys, chimpanzees, macaques, dogs, rats, frogs, and zebrafish. The function of renin in all organisms is similar, but the sequence and peptide length vary slightly.