Angiotensin-converting enzyme

Angiotensin I converting enzyme (peptidyl-dipeptidase A) 1
Available structures
1o86, 1o8a, 1uze, 1uzf, 2c6f, 2c6n, 2iul, 2iux, 2oc2
Identifiers
Symbols	ACE; ACE1; CD143; DCP; DCP1; MGC26566
External IDs	OMIM: 106180 MGI: 87874 HomoloGene: 37351
Gene ontology Molecular function • carboxypeptidase activity • peptidyl-dipeptidase A activity • zinc ion binding • hydrolase activity, acting on glycosyl bonds • chloride ion binding • metal ion binding Cellular component • membrane fraction • soluble fraction • plasma membrane • membrane • integral to membrane Biological process • proteolysis • metabolic process • blood pressure regulation
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1636	11421
Ensembl	ENSG00000159640	ENSMUSG00000020681
UniProt	P12821	Q3TU20
RefSeq	NM_000789 (mRNA)	NM_009598 (mRNA)
	NP_000780 (protein)	NP_033728 (protein)
Location	Chr 17: 58.91 - 58.94 Mb	Chr 11: 105.78 - 105.81 Mb
PubMed search	[1]	[2]

Angiotensin I-converting enzyme (ACE, EC 3.4.15.1), an exopeptidase, is a circulating enzyme that participates in the body's renin-angiotensin system (RAS), which mediates extracellular volume (i.e. that of the blood plasma, lymph and interstitial fluid), and arterial vasoconstriction. It is secreted by pulmonary and renal endothelial cells and catalyzes the conversion of decapeptide angiotensin I to octapeptide angiotensin II.^[1]

Functions

Schematic diagram of the renin-angiotensin-aldosterone system

Anatomical diagram of the renin-angiotensin system, showing role of ACE at the lungs.^[2]

It has two primary functions:

• ACE catalyses the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor in a substrate concentration dependent manner.^[3]
• ACE degrades bradykinin, a potent vasodilator, and other vasoactive peptides,^[4]

These two actions make ACE inhibition a goal in the treatment of conditions such as high blood pressure, heart failure, diabetic nephropathy, and type 2 diabetes mellitus. Inhibition of ACE (by ACE inhibitors) results in the decreased formation of angiotensin II and decreased metabolism of bradykinin, leading to systematic dilation of the arteries and veins and a decrease in arterial blood pressure. In addition, inhibiting angiotension 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.^[5]

Genetics & C and N Domains With Important Functional Difference

The ACE gene, ACE, encodes 2 isozymes. The somatic isozyme is expressed in many tissues, mainly in the lung, including vascular endothelial cells, epithelial kidney cells, and testicular Leydig cells, whereas the germinal is expressed only in sperm. Brain has ACE enzyme which takes part in local RAAS and converts Aβ42 ( plaquogenic ) to Aβ40( more soluble and removal ) forms of Beta amyloid ; latter is prdominentally a function of N domain portion on the ACE enzyme; Inhibition of ACE with ACE Inhibitors, especially Blood Brain Barrier crossing and with preferentially select N terminal activity would cause accumulation of Aβ42 which is plaquogenic causing progression of dementia; preferential C domain active BBB crossing ACE would likely have less of this latter effect.

See also

• Renin-angiotensin system
• ACE inhibitors

References

Further reading

v • d • e PDB Gallery 1o86: CRYSTAL STRUCTURE OF HUMAN ANGIOTENSIN CONVERTING ENZYME IN COMPLEX WITH LISINOPRIL.   1o8a: CRYSTAL STRUCTURE OF HUMAN ANGIOTENSIN CONVERTING ENZYME (NATIVE).   1uze: COMPLEX OF THE ANTI-HYPERTENSIVE DRUG ENALAPRILAT AND THE HUMAN TESTICULAR ANGIOTENSIN I-CONVERTING ENZYME   1uzf: COMPLEX OF THE ANTI-HYPERTENSIVE DRUG CAPTOPRIL AN THE HUMAN TESTICULAR ANGIOTENSIN I-CONVERTING ENZYME   2c6f: STRUCTURE OF HUMAN SOMATIC ANGIONTENSIN-I CONVERTING ENZYME N DOMAIN   2c6n: STRUCTURE OF HUMAN SOMATIC ANGIONTENSIN-I CONVERTING ENZYME N DOMAIN WITH LISINOPRIL   2iul: HUMAN TACE G13 MUTANT   2iux: HUMAN TACE MUTANT G1234   2oc2: Structure of testis ACE with RXPA380

External links

• MeSH Angiotensin+Converting+Enzyme