4apj

Structural highlights

Disease

[ACE_HUMAN] Genetic variations in ACE may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.^[1] Defects in ACE are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).^[2] Genetic variations in ACE are associated with susceptibility to microvascular complications of diabetes type 3 (MVCD3) [MIM:612624]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Defects in ACE are a cause of susceptibility to intracerebral hemorrhage (ICH) [MIM:614519]. A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke.^[3]

Function

[ACE_HUMAN] Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. [BNP_GLOBL] Blomhotin: inhibits the rabbit lung angiotensin-converting enzyme (ACE) with an IC(50) of 15 uM. Bradykinin-potentiating peptide A: causes no contraction of the rat gastric fundus smooth muscle even at high concentrations. Bradykinin-potentiating peptide B: inhibits the activity of the angiotensin-converting enzyme (ACE) by a preferential interaction with its C-domain. Also potentiates the hypotensive effects of bradykinin. Inhibits the rabbit lung ACE with an IC(50) of 1.1 uM. Bradykinin-potentiating peptide C: inhibits the activity of the angiotensin-converting enzyme (ACE) by interacting with the same potency to its C- and N-domains (PubMed:11994001). Inhibits the rabbit lung angiotensin-converting enzyme (ACE) with an IC(50) of 7.1 uM.^[4] Leu3-blomhotin: inhibits the rabbit lung angiotensin-converting enzyme (ACE) with an IC(50) of 46 uM. Synthetic Leu3-blomhotin contracts the rat gastric fundus smooth muscle in a rapid and transient manner. Bradykinin-potentiating peptide Ahb1: potentiates the bradykinin in vivo. Bradykinin-potentiating peptide Ahb2: does not show any bradykinin-potentiating effects. C-type natriuretic peptide: exhibits hypotensive and vasodepressor activity. Acts by activating natriuretic receptors (NPR1 and/or NPR2 and/or NPR3) (By similarity).

See Also

• Angiotensin-Converting Enzyme

References

1. ↑ Casas JP, Hingorani AD, Bautista LE, Sharma P. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch Neurol. 2004 Nov;61(11):1652-61. PMID:15534175 doi:61/11/1652
2. ↑ Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, Bouton JM, Feuillet F, Makni S, Ben Amar H, Laube G, Delezoide AL, Bouvier R, Dijoud F, Ollagnon-Roman E, Roume J, Joubert M, Antignac C, Gubler MC. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet. 2005 Sep;37(9):964-8. Epub 2005 Aug 14. PMID:16116425 doi:ng1623
3. ↑ Slowik A, Turaj W, Dziedzic T, Haefele A, Pera J, Malecki MT, Glodzik-Sobanska L, Szermer P, Figlewicz DA, Szczudlik A. DD genotype of ACE gene is a risk factor for intracerebral hemorrhage. Neurology. 2004 Jul 27;63(2):359-61. PMID:15277638
4. ↑ Cotton J, Hayashi MA, Cuniasse P, Vazeux G, Ianzer D, De Camargo AC, Dive V. Selective inhibition of the C-domain of angiotensin I converting enzyme by bradykinin potentiating peptides. Biochemistry. 2002 May 14;41(19):6065-71. PMID:11994001
5. ↑ Masuyer G, Schwager SL, Sturrock ED, Isaac RE, Acharya KR. Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptides. Sci Rep. 2012;2:717. doi: 10.1038/srep00717. Epub 2012 Oct 9. PMID:23056909 doi:http://dx.doi.org/10.1038/srep00717