Adenosine deaminase 1264968 224257399 2008-07-08T00:59:44Z ProteinBoxBot 3991663 Replaced protein Box Template with PBB Template for easy viewing. <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. --> {{PBB|geneid=100}} '''''Adenosine deaminase''''' (also known as '''ADA''') is an [[enzyme]] ({{EC number|3.5.4.4}}) involved in [[Purine#Metabolism|purine metabolism]]. It is needed for the breakdown of [[adenosine]] from food and for the turnover of [[nucleic acid]]s in tissues. ==Reactions== ADA irreversibly deaminates adenosine, converting it to the related [[nucleoside]] [[inosine]] by the removal of an [[amino]] group. <gallery> Image:A chemical structure.png|[[Adenosine]] Image:Inosine.svg|[[Inosine]] (observe missing nitrogen in upper left) </gallery> Inosine can then be deribosylated (removed from [[ribose]]) by another enzyme called [[purine nucleoside phosphorylase]] (PNP), converting it to [[hypoxanthine]]. ==Pathology== Mutations in the gene for adenosine deaminase causing it to not be expressed are one cause of [[severe combined immunodeficiency]] (SCID).<ref name="pmid17181544">{{cite journal |author=Sanchez JJ, Monaghan G, Børsting C, Norbury G, Morling N, Gaspar HB |title=Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry |journal=Ann. Hum. Genet. |volume=71 |issue=Pt 3 |pages=336–47 |year=2007 |pmid=17181544 |doi=10.1111/j.1469-1809.2006.00338.x}}</ref> [[Mutation]]s causing it to be overexpressed are one cause of [[hemolytic anemia]].<ref name="pmid3029177">{{cite journal |author=Chottiner EG, Cloft HJ, Tartaglia AP, Mitchell BS |title=Elevated adenosine deaminase activity and hereditary hemolytic anemia. Evidence for abnormal translational control of protein synthesis |journal=J. Clin. Invest. |volume=79 |issue=3 |pages=1001–5 |year=1987 |pmid=3029177 |doi=10.1172/JCI112866}}</ref> There is some evidence that a different allelle (ADA2) may lead to [[autism]].<ref name="pmid11121182">{{cite journal |author=Persico AM, Militerni R, Bravaccio C, ''et al'' |title=Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies |journal=Am. J. Med. Genet. |volume=96 |issue=6 |pages=784–90 |year=2000 |pmid=11121182 |doi=10.1002/1096-8628(20001204)96:6<784::AID-AJMG18>3.0.CO;2-7}}</ref> ==Isoforms== There are 2 [[isoforms]] of ADA: ADA1 and ADA2. * ADA1 is found in most body cells, particularly [[lymphocyte]]s and [[macrophage]]s, where it is present not only in the cytosol and nucleus but also as the ecto- form on the cell membrane attached to [[dipeptidyl peptidase-4]] (aka, CD26). * ADA2 was first identified in human spleen. It was subsequently found in other tissues including the macrophage where it co-exists with ADA1. The two isoforms regulate the ratio of adenosine to deoxyadenosine potentiating the killing of parasites. * {{Gene|ADAR}} is an RNA-specific ADA.<ref>{{cite journal |author=Keegan LP, Leroy A, Sproul D, O'Connell MA |title=Adenosine deaminases acting on RNA (ADARs): RNA-editing enzymes |journal=Genome Biol. |volume=5 |issue=2 |pages=209 |year=2004 |pmid=14759252 |doi=10.1186/gb-2004-5-2-209 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=395743}}</ref> * ADAT ({{Gene|ADAT1}}, {{Gene|ADAT2}}, {{Gene|ADAT3}}) is a [[tRNA]]-specific ADA, changing the tRNA to allow for a [[Wobble base pair|wobble base pairing]]. ==Clinical significance== ADA2 is the predominant form present in human [[blood plasma]] and is increased in many diseases, particularly those associated with the immune system: for example [[rheumatoid arthritis]], [[psoriasis]] and [[sarcoidosis]]. The plasma AD2 isoform is also increased in most cancers. Total plasma ADA can be measured using [[high performance liquid chromatography]], enzymatic or colorimetric techniques. Perhaps the simplest system is the measurement of the [[ammonia]] released from adenosine when broken down to inosine. After incubation of plasma with a buffered solution of adenosine the ammonia is reacted with a [[Berthelot reagent]] to form a blue colour which is proportionate to the amount of enzyme activity. To measure ADA2, [[EHNA|erythro-9-(2-hydroxy-3-nonyl) adenine]] (EHNA) is added prior to incubation so as to inhibit the enzymatic acivity of ADA1. It is the absence of ADA1 that causes SCID. ==See also== * [[Adenosine deaminase deficiency]] * [[ADAR]], a human gene encoding a RNA-specific adenosine deaminase ==References== {{reflist}} ==Further reading== {{refbegin | 2}} {{PBB_Further_reading | citations = *{{cite journal | author=da Cunha JG |title=[Adenosine deaminase. A pluridisciplinary enzyme] |journal=Acta médica portuguesa |volume=4 |issue= 6 |pages= 315–23 |year= 1992 |pmid= 1807098 |doi= }} *{{cite journal | author=Franco R, Casadó V, Ciruela F, ''et al.'' |title=Cell surface adenosine deaminase: much more than an ectoenzyme |journal=Prog. Neurobiol. |volume=52 |issue= 4 |pages= 283–94 |year= 1997 |pmid= 9247966 |doi=10.1016/S0301-0082(97)00013-0 }} *{{cite journal | author=Valenzuela A, Blanco J, Callebaut C, ''et al.'' |title=HIV-1 envelope gp120 and viral particles block adenosine deaminase binding to human CD26 |journal=Adv. Exp. Med. Biol. |volume=421 |issue= |pages= 185–92 |year= 1997 |pmid= 9330696 |doi= }} *{{cite journal | author=Moriwaki Y, Yamamoto T, Higashino K |title=Enzymes involved in purine metabolism--a review of histochemical localization and functional implications |journal=Histol. Histopathol. |volume=14 |issue= 4 |pages= 1321–40 |year= 1999 |pmid= 10506947 |doi= }} *{{cite journal | author=Hirschhorn R |title=Identification of two new missense mutations (R156C and S291L) in two ADA- SCID patients unusual for response to therapy with partial exchange transfusions |journal=Hum. Mutat. |volume=1 |issue= 2 |pages= 166–8 |year= 1993 |pmid= 1284479 |doi= 10.1002/humu.1380010214 }} *{{cite journal | author=Berkvens TM, van Ormondt H, Gerritsen EJ, ''et al.'' |title=Identical 3250-bp deletion between two AluI repeats in the ADA genes of unrelated ADA-SCID patients |journal=Genomics |volume=7 |issue= 4 |pages= 486–90 |year= 1990 |pmid= 1696926 |doi=10.1016/0888-7543(90)90190-6 }} *{{cite journal | author=Aran JM, Colomer D, Matutes E, ''et al.'' |title=Presence of adenosine deaminase on the surface of mononuclear blood cells: immunochemical localization using light and electron microscopy |journal=J. Histochem. Cytochem. |volume=39 |issue= 8 |pages= 1001–8 |year= 1991 |pmid= 1856451 |doi= }} *{{cite journal | author=Bielat K, Tritsch GL |title=Ecto-enzyme activity of human erythrocyte adenosine deaminase |journal=Mol. Cell. Biochem. |volume=86 |issue= 2 |pages= 135–42 |year= 1989 |pmid= 2770711 |doi=10.1007/BF00222613 }} *{{cite journal | author=Hirschhorn R, Tzall S, Ellenbogen A, Orkin SH |title=Identification of a point mutation resulting in a heat-labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency |journal=J. Clin. Invest. |volume=83 |issue= 2 |pages= 497–501 |year= 1989 |pmid= 2783588 |doi=10.1172/JCI113909 }} *{{cite journal | author=Murray JL, Perez-Soler R, Bywaters D, Hersh EM |title=Decreased adenosine deaminase (ADA) and 5'nucleotidase (5NT) activity in peripheral blood T cells in Hodgkin disease |journal=Am. J. Hematol. |volume=21 |issue= 1 |pages= 57–66 |year= 1986 |pmid= 3010705 |doi=10.1002/ajh.2830210108 }} *{{cite journal | author=Wiginton DA, Kaplan DJ, States JC, ''et al.'' |title=Complete sequence and structure of the gene for human adenosine deaminase |journal=Biochemistry |volume=25 |issue= 25 |pages= 8234–44 |year= 1987 |pmid= 3028473 |doi=10.1021/bi00373a017 }} *{{cite journal | author=Akeson AL, Wiginton DA, Dusing MR, ''et al.'' |title=Mutant human adenosine deaminase alleles and their expression by transfection into fibroblasts |journal=J. Biol. Chem. |volume=263 |issue= 31 |pages= 16291–6 |year= 1988 |pmid= 3182793 |doi= }} *{{cite journal | author=Glader BE, Backer K |title=Elevated red cell adenosine deaminase activity: a marker of disordered erythropoiesis in Diamond-Blackfan anaemia and other haematologic diseases |journal=Br. J. Haematol. |volume=68 |issue= 2 |pages= 165–8 |year= 1988 |pmid= 3348976 |doi=10.1111/j.1365-2141.1988.tb06184.x }} *{{cite journal | author=Petersen MB, Tranebjaerg L, Tommerup N, ''et al.'' |title=New assignment of the adenosine deaminase gene locus to chromosome 20q13 X 11 by study of a patient with interstitial deletion 20q |journal=J. Med. Genet. |volume=24 |issue= 2 |pages= 93–6 |year= 1987 |pmid= 3560174 |doi= }} *{{cite journal | author=Orkin SH, Goff SC, Kelley WN, Daddona PE |title=Transient expression of human adenosine deaminase cDNAs: identification of a nonfunctional clone resulting from a single amino acid substitution |journal=Mol. Cell. Biol. |volume=5 |issue= 4 |pages= 762–7 |year= 1985 |pmid= 3838797 |doi= }} *{{cite journal | author=Valerio D, Duyvesteyn MG, Dekker BM, ''et al.'' |title=Adenosine deaminase: characterization and expression of a gene with a remarkable promoter |journal=EMBO J. |volume=4 |issue= 2 |pages= 437–43 |year= 1985 |pmid= 3839456 |doi= }} *{{cite journal | author=Bonthron DT, Markham AF, Ginsburg D, Orkin SH |title=Identification of a point mutation in the adenosine deaminase gene responsible for immunodeficiency |journal=J. Clin. Invest. |volume=76 |issue= 2 |pages= 894–7 |year= 1985 |pmid= 3839802 |doi=10.1172/JCI112050 }} *{{cite journal | author=Daddona PE, Shewach DS, Kelley WN, ''et al.'' |title=Human adenosine deaminase. cDNA and complete primary amino acid sequence |journal=J. Biol. Chem. |volume=259 |issue= 19 |pages= 12101–6 |year= 1984 |pmid= 6090454 |doi= }} *{{cite journal | author=Valerio D, Duyvesteyn MG, Meera Khan P, ''et al.'' |title=Isolation of cDNA clones for human adenosine deaminase |journal=Gene |volume=25 |issue= 2-3 |pages= 231–40 |year= 1984 |pmid= 6198240 |doi=10.1016/0378-1119(83)90227-5 }} }} {{refend}} [[Category:EC 3.5.4]] {{hydrolase-stub}} {{Carbon-nitrogen non-peptide hydrolases}} {{Nucleotide metabolism}} [[ja:アデノシンデアミナーゼ]] [[pt:Adenosina deaminase]] {{PBB_Controls | update_page = yes | require_manual_inspection = no | update_protein_box = yes | update_summary = no | update_citations = yes }}