WordNet

any of several complex proteins that are produced by cells and act as catalysts in specific biochemical reactions
any of several vasoconstrictor substances (trade name Hypertensin) that cause narrowing of blood vessels (同)angiotonin, Hypertensin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/18 10:36:24」(JST)

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Angiotensin-converting enzyme (EC 3.4.15.1), or "ACE" indirectly increases blood pressure by causing blood vessels to constrict. It does that by converting angiotensin I to angiotensin II, which constricts the vessels. For this reason, drugs known as ACE inhibitors are used to lower blood pressure.

ACE is also known by the following names: dipeptidyl carboxypeptidase I, peptidase P, dipeptide hydrolase, peptidyl dipeptidase, angiotensin converting enzyme, kininase II, angiotensin I-converting enzyme, carboxycathepsin, dipeptidyl carboxypeptidase, "hypertensin converting enzyme" peptidyl dipeptidase I, peptidyl-dipeptide hydrolase, peptidyldipeptide hydrolase, endothelial cell peptidyl dipeptidase, peptidyl dipeptidase-4, PDH, peptidyl dipeptide hydrolase, and DCP.

ACE, angiotensin I and angiotensin II are part of the renin-angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. ACE is secreted in the lungs and kidneys by cells in the endothelium (inner layer) of blood vessels.^[1]

Functions

Schematic diagram of the renin–angiotensin–aldosterone system

Anatomical diagram of the renin-angiotensin system, showing the 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 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.^[5]

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).^[6]

Genetics and C and N domains function

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, whereas the germinal is expressed only in sperm. Brain tissue has ACE enzyme, which takes part in local RAAS and converts Aβ42 (which aggregates into plaques) to Aβ40 (which is thought to be less toxic) forms of beta amyloid. The latter is predominantly a function of N domain portion on the ACE enzyme. ACE inhibitors that cross the blood–brain barrier and have preferentially select N terminal activity may, therefore, cause accumulation of Aβ42 and progression of dementia.^{[citation needed]}

Pathology

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.
Serum levels are decreased in renal disease, obstructive pulmonary disease, and hypothyroidism.

Influence on athletic performance

ACE gene is a I/D polymorphism leading to the presence(I) or absence (D) the carriers of the ACE insertion allele of an alu repeat in intron 16 of the gene.^[7] With the insertion, observed higher maximum oxygen uptake (VO2max), increase in training, and increased muscle when paired with individuals carrying the deletion allele.
Individuals with the insertion are associated with long distance and endurance events. This is seen in studies that suggest that it is due to lower levels of angiotensin II. The deletion of the Alu increases angiotensin II that in turn increases the vasoconstriction of blood vessels. This is observed in short distance events and seen mostly in swimmers.^[8]

References

^ Kierszenbaum, Abraham L. (2007). Histology and cell biology: an introduction to pathology. Mosby Elsevier. ISBN 0-323-04527-8.
^ Page 866-867 (Integration of Salt and Water Balance) and 1059 (The Adrenal Gland) in: Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3.
^ Zhang R, Xu X, Chen T, Li L, Rao P (May 2000). "An assay for angiotensin-converting enzyme using capillary zone electrophoresis". Anal. Biochem. 280 (2): 286–90. doi:10.1006/abio.2000.4535. PMID 10790312.
^ Imig JD (March 2004). "ACE Inhibition and Bradykinin-Mediated Renal Vascular Responses: EDHF Involvement". Hypertension 43 (3): 533–5. doi:10.1161/01.HYP.0000118054.86193.ce. PMID 14757781.
^ Klabunde RE. "ACE-inhibitors". Cardiovascular Pharmacology Concepts. cvpharmacology.com. Retrieved 2009-03-26.
^ Boron and Boulpaed Medical Physiology 2nd edition Updated
^ Wang P, Fedoruk MN, Rupert JL (2008). "Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents?". Sports Med 38 (12): 1065–79. doi:10.2165/00007256-200838120-00008. PMID 19026021.
^ Costa AM, Silva AJ, Garrido ND, Louro H, de Oliveira RJ, Breitenfeld L (August 2009). "Association between ACE D allele and elite short distance swimming". Eur. J. Appl. Physiol. 106 (6): 785–90. doi:10.1007/s00421-009-1080-z. PMID 19458960.

External links

Proteopedia Angiotensin-converting_enzyme - the Angiotensin-Converting Enzyme Structure in Interactive 3D
Angiotensin Converting Enzyme at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 肺サルコイドーシスの臨床症状および診断 clinical manifestations and diagnosis of pulmonary sarcoidosis
2. アンギオテンシン変換酵素阻害剤とアンギオテンシン受容体拮抗剤との相違 differences between angiotensin converting enzyme inhibitors and receptor blockers
3. 急性心筋梗塞におけるアンギオテンシン変換酵素阻害剤：作用機序 angiotensin converting enzyme inhibitors in acute myocardial infarction mechanisms of action
4. アンギオテンシン変換酵素阻害剤およびアンギオテンシンII受容体拮抗剤の主な副作用 major side effects of angiotensin converting enzyme inhibitors and angiotensin ii receptor blockers
5. 心不全におけるアンギオテンシン変換酵素阻害剤およびアンギオテンシン受容体拮抗剤：作用機序 angiotensin converting enzyme inhibitors and receptor blockers in heart failure mechanisms of action

English Journal

Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress.

Clarke NE1, Belyaev ND1, Lambert DW2, Turner AJ1.Author information 1*School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.2†Integrated Biosciences, School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, U.K.AbstractACE2 (angiotensin-converting enzyme 2) counterbalances the actions of ACE (angiotensin-converting enzyme) by metabolizing its catalytic product, the vasoactive and fibrogenic peptide AngII (angiotensin II), into Ang-(1-7) [angiotensin-(1-7)]. Enhanced ACE2 expression may be protective in diabetes, cardiovascular disease and cancer. However, relatively little is known about the specific physiological factors regulating ACE2 expression. In the present paper, we show, by Western blotting and qPCR (quantitative real-time PCR), that ACE2 expression is increased under conditions of cell stress, including hypoxic conditions, IL (interleukin)-1β treatment and treatment with the AMP mimic AICAR (5-amino-4-imidazolecarboxamide riboside). The NAD+-dependent deacetylase SIRT1 (silent information regulator T1) was found to be up-regulated after AICAR treatment but, conversely, was down-regulated after IL-1β treatment. ChIP analysis demonstrated that SIRT1 bound to the ACE2 promoter and that binding was increased after AICAR treatment, but decreased after IL-1β treatment. Inhibition of SIRT1 activity ablated the AICAR-induced increase in ACE2. In conclusion, we have established that the expression of the ACE2 transcript is controlled by the activity of SIRT1 under conditions of energy stress.
Clinical science (London, England : 1979).Clin Sci (Lond).2014 Apr 11;126(7):507-16. doi: 10.1042/CS20130291.
ACE2 (angiotensin-converting enzyme 2) counterbalances the actions of ACE (angiotensin-converting enzyme) by metabolizing its catalytic product, the vasoactive and fibrogenic peptide AngII (angiotensin II), into Ang-(1-7) [angiotensin-(1-7)]. Enhanced ACE2 expression may be protective in diabetes, c
PMID 24147777

Role of angiotensin-converting enzyme 2 (ACE2) in diabetic cardiovascular complications.

Patel VB, Parajuli N, Oudit GY.AbstractDiabetes mellitus results in severe cardiovascular complications, and heart disease and failure remain the major causes of death in patients with diabetes. Given the increasing global tide of obesity and diabetes, the clinical burden of diabetes-induced cardiovascular disease is reaching epidemic proportions. Therefore urgent actions are needed to stem the tide of diabetes which entails new prevention and treatment tools. Clinical and pharmacological studies have demonstrated that AngII (angiotensin II), the major effector peptide of the RAS (renin-angiotensin system), is a critical promoter of insulin resistance and diabetes mellitus. The role of RAS and AngII has been implicated in the progression of diabetic cardiovascular complications and AT1R (AngII type 1 receptor) blockers and ACE (angiotensin-converting enzyme) inhibitors have shown clinical benefits. ACE2, the recently discovered homologue of ACE, is a monocarboxypeptidase which converts AngII into Ang-(1-7) [angiotensin-(1-7)] which, by virtue of its actions on the MasR (Mas receptor), opposes the effects of AngII. In animal models of diabetes, an early increase in ACE2 expression and activity occurs, whereas ACE2 mRNA and protein levels have been found to decrease in older STZ (streptozotocin)-induced diabetic rats. Using the Akita mouse model of Type 1 diabetes, we have recently shown that loss of ACE2 disrupts the balance of the RAS in a diabetic state and leads to AngII/AT1R-dependent systolic dysfunction and impaired vascular function. In the present review, we will discuss the role of the RAS in the pathophysiology and treatment of diabetes and its complications with particular emphasis on potential benefits of the ACE2/Ang-(1-7)/MasR axis activation.
Clinical science (London, England : 1979).Clin Sci (Lond).2014 Apr 1;126(7):471-82. doi: 10.1042/CS20130344.
Diabetes mellitus results in severe cardiovascular complications, and heart disease and failure remain the major causes of death in patients with diabetes. Given the increasing global tide of obesity and diabetes, the clinical burden of diabetes-induced cardiovascular disease is reaching epidemic pr
PMID 24329564

Novel angiotensin I-converting enzyme inhibitory peptides derived from edible mushroom Agaricus bisporus (J.E. Lange) Imbach identified by LC-MS/MS.

Lau CC, Abdullah N, Shuib AS, Aminudin N.Author information Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.AbstractAngiotensin I-converting enzyme (ACE) inhibitors derived from foods are valuable auxiliaries to agents such as captopril. Eight highly functional ACE inhibitory peptides from the mushroom, Agaricus bisporus, were identified by LC-MS/MS. Among these peptides, the most potent ACE inhibitory activity was exhibited by AHEPVK, RIGLF and PSSNK with IC₅₀ values of 63, 116 and 129 μM, respectively. These peptides exhibited high ACE inhibitory activity after gastrointestinal digestion. Lineweaver-Burk plots suggested that AHEPVK and RIGLF act as competitive inhibitors against ACE, whereas PSSNK acts as a non-competitive inhibitor. Mushrooms can be a good component of dietary supplement due to their readily available source and, in addition, they rarely cause food allergy. Compared to ACE inhibitory peptides isolated from other edible mushrooms, AHEPVK, RIGLF and PSSNK have lower IC₅₀ values. Therefore, these peptides may serve as an ideal ingredient in the production of antihypertensive supplements.
Food chemistry.Food Chem.2014 Apr 1;148:396-401. doi: 10.1016/j.foodchem.2013.10.053. Epub 2013 Oct 24.
Angiotensin I-converting enzyme (ACE) inhibitors derived from foods are valuable auxiliaries to agents such as captopril. Eight highly functional ACE inhibitory peptides from the mushroom, Agaricus bisporus, were identified by LC-MS/MS. Among these peptides, the most potent ACE inhibitory activity w
PMID 24262574

Japanese Journal

糖尿病の降圧はRAS阻害薬を使うべき? (特集循環器治療の"常識"と"非常識")

循環器内科 = Cardioangiology 78(6), 568-572, 2015-12
NAID 40020691183

レニン-アンジオテンシン-アルドステロン系を阻害する薬物 : ACE阻害薬とAT₁受容体拮抗薬の特徴

日本獣医腎泌尿器学会誌 8(1), 60-65, 2015-11
NAID 40020657678

今月の症例 ACE阻害薬による血管性浮腫が疑われた舌腫脹の1例

日本内科学会雑誌 104(7), 1460-1463, 2015-07-10
NAID 40020541130

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リンク元	「アンジオテンシン変換酵素」
拡張検索	「angiotensin-converting enzyme」「angiotensin converting enzyme inhibitor」
関連記事	「angiotensin」

「アンジオテンシン変換酵素」

Angiotensin I converting enzyme
	Rendering of ACE from PDB 1O86
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1O86, 1O8A, 1UZE, 1UZF, 2C6F, 2C6N, 2IUL, 2IUX, 2OC2, 2XY9, 2XYD, 2YDM, 3BKK, 3BKL, 3L3N, 3NXQ, 4APH, 4APJ, 4BXK, 4BZR, 4BZS, 4C2N, 4C2O, 4C2P, 4C2Q, 4C2R, 4CA5, 4CA6
Identifiers
Symbols	ACE ; ACE1; CD143; DCP; DCP1; ICH; MVCD3
External IDs	OMIM: 106180 MGI: 87874 HomoloGene: 37351 ChEMBL: 1808 GeneCards: ACE Gene
EC number	3.4.15.1
Gene ontology
Molecular function	• actin binding; • endopeptidase activity; • carboxypeptidase activity; • protein binding; • drug binding; • metallopeptidase activity; • exopeptidase activity; • tripeptidyl-peptidase activity; • peptidyl-dipeptidase activity; • zinc ion binding; • chloride ion binding; • mitogen-activated protein kinase kinase binding; • bradykinin receptor binding; • mitogen-activated protein kinase binding;
Cellular component	• extracellular region; • extracellular space; • lysosome; • endosome; • plasma membrane; • external side of plasma membrane; • integral component of membrane; • extracellular exosome;
Biological process	• kidney development; • blood vessel remodeling; • angiotensin maturation; • angiotensin catabolic process in blood; • regulation of renal output by angiotensin; • neutrophil mediated immunity; • antigen processing and presentation of peptide antigen via MHC class I; • regulation of systemic arterial blood pressure by renin-angiotensin; • spermatogenesis; • regulation of blood pressure; • regulation of smooth muscle cell migration; • regulation of vasoconstriction; • mononuclear cell proliferation; • regulation of vasodilation; • hormone catabolic process; • peptide catabolic process; • cellular protein metabolic process; • beta-amyloid metabolic process; • arachidonic acid secretion; • heart contraction; • regulation of angiotensin metabolic process; • hematopoietic stem cell differentiation; • positive regulation of protein tyrosine kinase activity; • cell proliferation in bone marrow; • positive regulation of peptidyl-tyrosine autophosphorylation; • regulation of hematopoietic stem cell proliferation; • negative regulation of gap junction assembly; • positive regulation of peptidyl-cysteine S-nitrosylation;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

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Angiotensin-converting enzyme
Identifiers
EC number	3.4.15.1
CAS number	9015-82-1
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
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PMC	articles
PubMed	articles
NCBI	proteins