Enzymes renin

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

Although the kidneys are not considered endocrine glands per se, they are involved in hormone production. Erythropoietin is a peptide hormone that stimulates red blood cell production in bone marrow. Its primary source is the kidneys. Erythropoietin is secreted in response to renal hypoxia. Chronic renal disease may impair the secretion of erythropoietin, leading to development of anemia. The kidneys also produce enzymes. The enzyme renin is part of the renin-angiotensin-aldosterone system. As will be discussed, these substances play an important role in the regulation of plasma volume and therefore blood pressure. Other renal enzymes are needed for the conversion of vitamin D into its active form, 1,25-d i hyd ro xyv itamin D3, which is involved with calcium balance. 

The natural blood globulin, angiotensinogen, Is converted by the proteolytic kidney enzyme, renin, to the decapeptide angiotensin 1. This substance is not a pressor agent but is cleaved by plasma converting enzyme to the powerful vasoconstrictor angiotensin II, an octapeptide. 

In addition to their involvement in excretion and metabolism, the kidneys also have endocrine functions. They produce the hormones erythropoietin and calcitriol and play a decisive part in producing the hormone angiotensin II by releasing the enzyme renin. Renal prostaglandins (see p. 390) have a local effect on Na resorption. 

The peptide hormone angiotensin II is not synthesized in a hormonal gland, but in the blood. The kidneys take part in this process by releasing the enzyme renin. 

The three protein pressor substances are renin, a prolonged pressor substance found in shock, and vasoexcitor material. Apparently they are different substances. Renin is the best understood (10). Its reaction with a globulin substrate to form hypertensin or angiotonin suggests that it is a proteolytic enzyme. Renin has been considerably concentrated, but has not been purified. The stimulus for its release by the kidney is a reduction of renal blood flow just how this comes about is unknown. 

A second peptide is pepsitensin, formed by peptic digestion of the substrate of renin (13). It represents an interesting type reaction similar to that of renin. Because two proteolytic enzymes, renin and pepsin, act on a protein to produce vasoconstrictor substances, the substrate must have peculiar structural properties conducive to formation of these substances when broken down. The pharmacology of pepsitensin has not been ex-... 

Despite its being far upsteam in the pathway shown in Scheme 2.2, the enzyme renin has recently emerged as a viable target for hypertension drugs. Aliskiren (Tekturna, 2.14) is a renin inhibitor and was approved by the U.S. Food and Drug Administration (FDA) in... 

Characterization of HIV-1 protease as a member of the aspartic acid protease family provided the rationale for most of the efforts to design inhibitors (Kohl et al, 1988 Krausslich et al., 1988 Navia et al., 1989 Pearl and Taylor, 1987). Previous efforts to develop therapeutically useful inhibitors of the mechanistically related enzyme renin had demonstrated that potent inhibitors could be prepared by replacing the scissile amide bond of a substrate analogue with a nonhydrolyzable isostere to mimic the tetrahedral intermediate or transition state involved in amide hydrolysis (Greenlee, 1990). Although several dipeptide isosteres have been used to successfully generate highly potent HIV-1 protease inhibitors, a relatively small number have resulted in compounds that reached clinical development. 

Angiotensin 11 is an octapeptide derived from biologically inactive decapeptide angiotensin 1, which comes from angiotensino-gen through the cleavage by the kidney enzyme renin. It is... 

The release of the primaiy mineralocorticoid aldosterone depends only slightly on ACTH. Aldosterone is an active part of the angiotensin-ienin-blood pressure cycle that controls blood volume. A decrease in blood volume. stimulates the kidneys to. secrete the enzyme renin. Renin, in turn, con-terts angiotensinogen to angiotensin, which stimulates the adrenal cortex to release aldosterone. Aldosterone then causes the kidneys to retain sodium, and blood volume increases. When the blood volume has increased sufTicicntly. renin production decreases, until blocxl volume drops again. 

Aspartyl proteases Bacteria, human Hypertension converting enzyme Renin 83,84,292 ... 

One of the newest and potentially most interesting areas for chemotherapy is the inhibition of proteases. This is of intense pharmaceutical interest for the management of high blood pressure and of viral diseases. The difficulty with this approach lies in the fact that the proteases use common mechanisms in the mammalian host and microorganisms. Nevertheless, specificity of inhibition has been achieved for the mammalian enzyme renin for the control of high blood pressure and for the protease used for replication of the human immunodeficiency virus which causes AIDS. For this reason, there is reason to be encouraged that inhibition of proteases in parasitic organisms will be an effective means of chemotherapy. 

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