Alpha 1-antitrypsine 207997 30758992 2008-06-18T13:45:44Z POMPIERS 62265 /* Rôle dans les maladies */ {{ébauche|médecine}} [[Image:A1AT.png|200px|right|Alpha 1-antitrypsin]] L''''alpha 1-antitrypsine''' ou '''α<sub>1</sub>-antitrypsine''' ('''A1AT''') est un [[inhibiteur de la sérine protéase ]] (serpin). Elle protège les tissus contre des [[enzyme]]s produites par des cellules inflammatoires, particulièrement l'[[élastase]]. On la trouve dans le [[sang]] humain à des taux de 1,5 à 3,5 [[gramme]]s/[[litre]]. ==Fonction== L'alpha-1 antitrypsine est une [[protéine]] sécrétée par le [[foie]]. Elle est présente dans le sang , pour aller vers les poumons, pour s'opposer à l'action d'une enzyme, qu'est l'[[élastase]]. Cette enzyme-là est libérée par les [[leucocyte]]d en cas d'infection , par exemple. ==Rôle dans les maladies== * élévation de sa clairance lors d'une diarrhée motrice d'origine exsudative * Un déficit peut causer de l'emphysème en de rares cas : Quand il y a déficit en alpha-1 antitrypsine , l'action de l'élastase n'est plus inhibée, elle détruit le tissu pulmonaire sans en être empéchée , tout cela entraînant la formation d'un [[emphysème pulmonaire]]. <!-- Disorders of the enzyme include [[alpha 1-antitrypsin deficiency]], a [[hereditary disorder]] in which lack of alpha 1-antitrypsin leads to uninhibited tissue breakdown during [[inflammation]]. This causes [[emphysema|pulmonary emphysema]] and leads to [[cirrhosis|liver cirrhosis]] in severe cases. A remarkable form of ''Pi'', termed ''Pi''<sub>Pittsburgh</sub>, functions as an [[antithrombin]] (a related [[serine protease inhibitor|serpin]]), due to a mutation ([[Methionine|Met]]358[[Arginine|Arg]]). One patient with this abnormality has been described; he died of a lethal [[bleeding]] diathesis. This disorder proves the point that the serine protease inhibitors have a closely related structure. --> ==Nomenclature== <!-- The [[enzyme]] is called "antitrypsin" because of its ability to [[covalent]]ly bind and irreversibly inactivate the enzyme [[trypsin]]. (Trypsin, a type of [[peptidase]], is a digestive enzyme active in the [[duodenum]] and elsewhere.) The term "alpha 1" refers to the enzyme's behaviour on [[protein electrophoresis]]. On electrophoresis, the protein component of the blood is separated by [[electric current]]. There are several "clusters", the first being [[albumin]], the second being the ''alpha'', the third ''beta'' and the fourth ''gamma'' ([[immunoglobulin]]s). The non-albumin proteins are referred to as [[globulin]]s. The ''alpha'' region can be further divided into two sub-regions, termed "1" and "2". Alpha 1-antitrypsin is the main [[enzyme]] of the [[alpha-globulin]] 1 region. Another name used is ''alpha-1 proteinase inhibitor'' (α<sub>1</sub>-PI). --> ==Génétique== <!-- The [[gene]] is located on the long arm of the fourteenth [[chromosome]] (14q32.1). Over 80 different versions of α<sub>1</sub>-antitrypsin have been described in various populations. North-West [[Europe]]ans are most at risk for carrying a deviant form of A1AT. --> ==Analyse== <!-- As [[protein]] [[electrophoresis]] is imprecise, A1AT is analysed by [[electrofocusing]] (isoelectric focusing analysis), where the protein is passed along a [[pH]] gradient. Normal A1AT is termed "M", as it is neutral and does not run very far. Other variants are less functional, and are termed A-L and N-Z, dependent on whether they run more proximal or more distal to the M band. The presence of deviant bands on [[electrofocusing]] can signify the presence of [[alpha 1-antitrypsin deficiency]]. As every person has two [[allele|copies]] of the A1AT [[gene]], a [[heterozygote]] (with two different copies of the gene), will have two different bands showing on electrofocusing. In [[blood test]] results, the [[electrofocusing]] results are notated as in PiMM, where Pi stands for [[protease inhibitor (biology)|protease inhibitor]] and "MM" is the banding pattern of that patient. ''Alpha 1-antitrypsin'' levels depend on the [[phenotype]], as deviant forms are excreted inefficiently by the [[liver]] and [[polymer]]ise in the [[endoplasmic reticulum]] : * PiMM: 100% (normal) * PiMS: 80% * PiSS: 60% * PiMZ: 60% * PiSZ: 40% * PiZZ: 10-15% (severe [[alpha 1-antitrypsin deficiency]]) The non-M [[allele]]s are all the product of [[mutation]]s in the "normal" ([[wild type]]) M variant. * PiZ is caused by a [[glutamate]] to [[lysine]] mutation on position 342. * PiS is caused by a [[glutamate]] to [[valine]] mutation on position 264. * Other, rarer forms have been described; in all, there are over 80 variants. --> ==Usage thérapeutique== <!-- [[Recombinant]] alpha 1-antitrypsin is not yet commercially available, but is under investigation as a therapeutic modality in congenital deficiency. Therapeutic concentrates are prepared from the [[blood plasma]] of blood donors. --> ==Historique== <!-- The possibility of [[allele|allelic]] variants of A1AD leading to disease was first investigated by Dr U. Axelsson and Dr C.B. Laurell in 1965. --> ==Sources== * U. Axelsson, CB Laurell, « Hereditary variants of serum alpha-1-antitrypsin », dans ''Am. J. Hum. Genet.'' 17 (1965), 466-472. PMID 4158556. * DL DeMeo, EK Silverman, « α1-Antitrypsin deficiency; 2: Genetic aspects of α1-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk », dans ''Thorax'', 59 (2004), 259–264 {{lire en ligne|doi=10.1136/thx.2003.006502|langue=en}}. * PG Gettins, « Serpin Structure, Mechanism, and Function », dans ''Chem. Rev.'', 102 (2002), 4751-4803 {{lire en ligne|doi=10.1021/cr010170+|langue=en}}. ==Liens externes== * Swiss-Prot [http://ca.expasy.org/cgi-bin/niceprot.pl?P01009 P01009] {{Portail médecine}} [[Catégorie:enzyme]] [[de:Α-1-Antitrypsin]] [[en:Alpha 1-antitrypsin]] [[es:Alfa 1-antitripsina]] [[he:אנטיטריפסין אלפא-1]] [[nl:Alfa 1-antitrypsine]] [[nn:Α₁-antitrypsin]] [[pl:Alfa1-antytrypsyna]] [[tr:AAT]]