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.
ACE converts the hormone angiotensin I to the active vasoconstrictor angiotensin II.
Therefore, ACE indirectly increases blood pressure by causing blood vessels to constrict.
Inhibitors of ACE are widely used as pharmaceutical drugs for treatment of cardiovascular diseases.
Chromosome 17.
ACE is located mainly in the capillaries of the lungs but can also be found in endothelial and kidney epithelial cells.
ACE functions in the degradation of bradykinin, substance P and amyloid beta-proteinIt hydrolyzes peptides by the removal of a dipeptide from the C-terminus.
It converts the inactive decapeptide angiotensin I to the octapeptide angiotensin II by removing the dipeptide His-Leu.
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.
ACE that generates a vasoconstrictor (ANG II) also disposes of vasodilators, bradykinin.
ACE is a zinc metalloproteinase.
The zinc ion is essential to its activity, and ACE can be inhibited by metal-chelating agents.
Lisinopril is a competitive inhibitor to ACE, since it has a similar structure to angiotensin I and binds to the active site of ACE.
The ACE gene, ACE, encodes two isozymes.
The somatic isozyme is expressed in many tissues: mainly in the lung, including vascular endothelial cells, epithelial kidney cells, and testicular Leydig cells.
The germinal isoenzyme is expressed only in sperm.
Brain tissue has ACE enzyme, which takes part in local RAS and converts Aβ42, which aggregates into plaques, to Aβ40, thought to be a less toxic form of beta amyloid.
ACE inhibitors that cross the blood brain barrier and have preferentially selected may therefore cause accumulation of Aβ42 and progression of dementia.
ACE inhibitors are widely used in the treatment of conditions such as high blood pressure, heart failure, diabetic nephropathy, and type 2 diabetes mellitus.
ACE inhibitors inhibit ACE competitively, decreasing 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.
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.
Alzheimer patients usually show higher ACE levels in their brain.
It is possible ACE inhibitors that are able to pass the blood-brain-barrier (BBB) and 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.
It is suggested 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.
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 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, miliary tuberculosis, and some patients with extensive plaque psoriasis.
Serum ACE levels are decreased in renal disease, obstructive pulmonary disease, and hypothyroidism.
The angiotensin converting enzyme gene has more than 160 polymorphisms.
Different genotypes of angiotensin converting enzyme can lead to varying influence on athletic performance.
The DD genotype is associated with higher plasma levels of the ACE protein, the DI genotype with intermediate levels, and II with lower levels.
During physical exercise, there are higher levels of the ACE for D-allele carriers, hence higher capacity to produce angiotensin II, the blood pressure will increase sooner than for I-allele carriers, resulting in a lower maximal heart rate and lower maximum oxygen uptake (VO2max).
D-allele carriers have a 10% increased risk of cardiovascular diseases.
The D-allele is associated with a greater increase in left ventricular growth in response to training compared to the I-allele.
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 I allele is found with increased frequency in elite runners, rowers and cyclists.
Short distance swimmers show an increased frequency of the D-allele, since their discipline relies more on strength than endurance.