Адам ағзасындағы ангиотензин түрлендіргіш ферменті

Mammalian protein found in humans

Angiotensin converting enzyme , or ACE, is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasoconstrictor angiotensin II. Therefore, ACE indirectly increases blood pressure by causing blood vessels to constrict. ACE inhibitors are widely used as pharmaceutical drugs for treatment of cardiovascular diseases. Other lesser known functions of ACE are degradation of bradykinin, substance P and amyloid beta protein.

ACE hydrolyzes peptides by the removal of a dipeptide from the C terminus. Likewise it converts the inactive decapeptide angiotensin I to the octapeptide angiotensin II by removing the dipeptide His Leu. ACE is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. Angiotensin II is a potent vasoconstrictor in a substrate concentration dependent manner. Angiotensin II binds to the type 1 angiotensin II receptor (AT1), which sets off a number of actions that result in vasoconstriction and therefore increased blood pressure. ACE is also part of the kinin–kallikrein system where it degrades bradykinin, a potent vasodilator, and other vasoactive peptides. Kininase II is the same as angiotensin converting enzyme. Thus, the same enzyme (ACE) that generates a vasoconstrictor (ANG II) also disposes of vasodilators (bradykinin). The zinc center catalyses the peptide hydrolysis. Reflecting the critical role of zinc, ACE can be inhibited by metal chelating agents. [[File:ACE in complex with inhibitor lisinopril. png|thumb|center|400px|ACE in complex with inhibitor lisinopril, zinc cation shown in grey, chloride anions in yellow. Based on PyMOL rendering of PDB 1o86. The picture shows that lisinopril is a competitive inhibitor, since it and angiotensin I are similar structurally. Both bind to the active site of ACE. The structure of the ACE lisinopril complex was confirmed by X ray crystallography. The function of the chloride ion is very complex and is highly debated. The anion activation by chloride is a characteristic feature of ACE. It was experimentally determined that the activation of hydrolysis by chloride is highly dependent on the substrate. While it increases hydrolysis rates for e. g. Hip His Leu it inhibits hydrolysis of other substrates like Hip Ala Pro. That results in the decreased formation of angiotensin II and decreased metabolism of bradykinin, which leads to systematic dilation of the arteries and veins and a decrease in arterial blood pressure. In addition, inhibiting angiotensin II formation diminishes angiotensin II mediated aldosterone secretion from the adrenal cortex, leading to a decrease in water and sodium reabsorption and a reduction in extracellular volume. ACE's effect on Alzheimer's disease is still highly debated. Alzheimer patients usually show higher ACE levels in their brain. Some studies suggest that ACE inhibitors that are able to pass the blood brain barrier (BBB) could enhance the activity of major amyloid beta peptide degrading enzymes like neprilysin in the brain resulting in a slower development of Alzheimer's disease. More recent research suggests that ACE inhibitors can reduce risk of Alzheimer's disease in the absence of apolipoprotein E4 alleles (ApoE4), but will have no effect in ApoE4 carriers. Another more recent hypothesis is that higher levels of ACE can prevent Alzheimer's. It is assumed that ACE can degrade beta amyloid in brain blood vessels and therefore help prevent the progression of the disease. A negative correlation between the ACE1 D allele frequency and the prevalence and mortality of COVID 19 has been established.

Elevated levels of ACE are also found in sarcoidosis, and are used in diagnosing and monitoring this disease. Elevated levels of ACE are also found in leprosy, hyperthyroidism, acute hepatitis, primary biliary cirrhosis, diabetes mellitus, multiple myeloma, osteoarthritis, amyloidosis, Gaucher disease, pneumoconiosis, histoplasmosis and miliary tuberculosis. It is also noted in some patients with extensive plaque psoriasis. Serum levels are decreased in renal disease, obstructive pulmonary disease, and hypothyroidism.

The angiotensin converting enzyme gene has more than 160 polymorphisms described as of 2018. Studies have shown that different genotypes of angiotensin converting enzyme can lead to varying influence on athletic performance. The rs1799752 I/D polymorphism consists of either an insertion (I) or absence (D) of a 287 base pair alanine sequence in intron 16 of the gene. On the other hand, I allele carriers usually show an increased maximal heart rate due to lower ACE levels, higher maximum oxygen uptake and therefore show an enhanced endurance performance.

The enzyme was reported by Leonard T. Skeggs Jr. in 1956. The crystal structure of human testis ACE was solved in the year 2002 by R. Natesh, S. Schwager & E. Sturrock in the lab of K. Ravi Acharya. It is located mainly in the capillaries of the lungs but can also be found in endothelial and kidney epithelial cells.