Angiotensin-converting enzyme function

Angiotensin converting enzyme (ACE) plays a central role in cardiovascular hemostasis. Its major function is the generation of angiotensin (ANG) II from ANGI and the degradation of bradykinin. Both peptides have profound impact on the cardiovascular system and beyond. ACE inhibitors are used to decrease blood pressure in hypertensive patients, to improve cardiac function, and to reduce work load of the heart in patients with cardiac failure. 

The family of apelin peptides is derived from a single gene, activate a single G-protein-coupled receptor and are substrates for the angiotensin converting enzyme-2 (ACE2). Apelins regulate cardiovascular function and fluid homeostasis. The apelin receptor also functions as a co-receptor for infection of CD4-positive cells by human immunodeficiency vims ( HIV). 

ACE-I, angiotensin-converting enzyme inhibitors ARB, angiotensin-receptor blockers AZA, azathioprine CMV, cytomegalovirus CPK, creatinine phos-phokinase CSA, cyclosporine HMG-CoA, 3-hydroxy 3-methylglutaryl coenzyme A reductase K+, potassium LFTs, liver function tests Rl, renal insufficiency SCr, serum creatinine SRL, sirolimus TAC, tacrolimus TMP-SMX, trimethoprim-sulfamethoxazole. 

Tian B, Meng QC, Chen Y-F, Krege JH, Smithies O, Oparil S. Blood pressures and cardiovascular homeostasis in mice having reduced or absent angiotensin-converting enzyme gene function. Hypertension 1997 30[part I] 128—133. 

Angiotensin converting enzymes- inhibitors (ACE-inhibitors) are a group of drugs that are very potent in dilating the blood vessels and through this mechanism lower the blood pressure. Therefore they can also improve heart function in patients with heart failure. In some cases they are also used for preventing renal failure in persons with hypertension and/or diabetes. Paradoxically, this later use of ACE-inhibitors... 

There have been sustained efforts in recent years to use the carrier systems of the brush-border membrane of intestinal mucosa to increase absorption of orally administered drugs [29] [30]. One system of particular interest is the intestinal peptide carrier (hPEPTl) whose physiological function is the absorption of di- and tripeptides and whose xenobiotic substrates include /3-lactam antibiotics, renin inhibitors, and angiotensin-converting enzyme (ACE) inhibitors [31]. 

Angiotensin converting enzyme (ACE) is an important enzyme for the regulation of blood pressure, ft exists in two forms the somatic form has 1277 amino acids, while the sperm cell form has 701 amino acids. The somatic form consists of two domains the carboxy-terminal (C) domain and the amino-terminal (N) domain. The sperm cell form consists of only the C domain. Studies have shown that the C domain is the dominant angiotensin converting site for controlling blood pressure and cardiovascular functions. 

Much of the recent work on the use of anodic amide oxidation reactions has focused on the utility of these reactions for functionalizing amino acids and for synthesizing peptide mimetics [13]. For example, in work related to the cyclization strategy outlined in Scheme 3, the anodic amide oxidation reaction has been used to construct a pair of angiotensin-converting enzyme inhibitors [14]. The retrosynthetic analysis for this route is outlined in Scheme 4. In this work, the anodic oxidation reaction was used to functionalize either a proline or a pipercolic add derivative and then the resulting methoxylated amide used to construct the bicyclic core of the desired inhibitor. A similar approach has recently been utilized to construct 6,5-bicyclic lactam building blocks for... 

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor and ACE inhibitors should be avoided during pregnancy. ACE inhibitors may adversely affect fetal and neonatal blood pressure control and renal function. They may also cause neonatal skull defects. 

Angiotensin-converting enzyme inhibitors should be used with caution in patients taking diuretics because of an enhanced hypotensive effect. Angiotensin-converting enzyme inhibitors should also be used with caution in patients with renal impairment. Renal function needs to be monitored in patients with renovascular disease. 

Some patients seem to have an inherent genetic susceptibility to restenosis following coronary stent implantation. Research has shown that patients homozygous for the deletion D) allele of angiotensin converting enzyme ACE) gene polymorphism lack functional enzyme and are at increased risk. These patients have ele-... 

The heritability of essential hypertension is estimated to be about 30%. Mutations in several genes have been linked to various rare causes of hypertension. Functional variations of the genes for angiotensinogen, angiotensin-converting enzyme (ACE), the 2 adrenoceptor, and a adducin (a cytoskeletal protein) appear to contribute to some cases of essential hypertension. 

E. M., Gallop, M. A. (1995) Combinatorial organic synthesis of highly functionalized pyrrolidines identification of a potent angiotensin converting enzyme inhibitor from a mercaptoacyl proline library. J Am Chem Soc 117, 7029-7030. 

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