View source for Alanine transaminase

{{Short description|Mammalian protein}}
{{Infobox enzyme
| EC_number = 2.6.1.2
| CAS_number = 9000-86-6
| GO_code = 0004021
| image =Human alanine transaminase 2 PDB 3IHJ.png
| caption =Human alanine transaminase 2 homodimer bound to PLP. {{PDB|3IHJ}}
|name=Alanine transaminase}}

'''Alanine aminotransferase''' ('''ALT''' or '''ALAT'''), formerly '''alanine transaminase''' ('''ALT'''),<ref name=":0" /> and even earlier referred to as '''serum glutamate-pyruvate transaminase''' ('''GPT''') or '''serum glutamic-pyruvic transaminase''' ('''SGPT'''), is a [[transaminase]] [[enzyme]] ({{EC number|2.6.1.2}}) that  was first characterized in the mid-1950s by Arthur Karmen and colleagues.<ref>{{cite journal | vauthors = Karmen A, Wroblewski F, Ladue JS | title = Transaminase activity in human blood | journal = The Journal of Clinical Investigation | volume = 34 | issue = 1 | pages = 126–31 | date = January 1955 | pmid = 13221663 | pmc = 438594 | doi = 10.1172/JCI103055 }}</ref> ALT is found in [[blood plasma|plasma]] and in various body tissues but is most common in the [[liver]]. It catalyzes the two parts of the [[alanine cycle]]. Serum ALT level, serum AST ([[aspartate transaminase]]) level, and their ratio ([[AST/ALT ratio]]) are routinely measured clinically as [[biomarker]]s for liver health.<ref>{{Cite journal |last1=Djakpo |first1=Dodji Kossi |last2=Wang |first2=Zhi Quan |last3=Shrestha |first3=Merina |date=2020-12-26 |title=The significance of transaminase ratio (AST/ALT) in acute myocardial infarction |url=https://amsad.termedia.pl/The-significance-of-transaminase-ratio-AST-ALT-in-acute-myocardial-infarction,125739,0,2.html |journal=Archives of Medical Science – Atherosclerotic Diseases |volume=5 |issue=1 |pages=279–283 |doi=10.5114/amsad.2020.103028 |pmid=33644486 |issn=2451-0629|pmc=7885810 }}</ref>

The [[biological half-life|half-life]] of ALT in the circulation approximates 47 hours.<ref name="Giannini pp. 367–379">{{cite journal | vauthors = Giannini EG, Testa R, Savarino V | title = Liver enzyme alteration: a guide for clinicians | journal = Canadian Medical Association Journal | volume = 172 | issue = 3 | pages = 367–79 | date = February 2005 | pmid = 15684121 | pmc = 545762 | doi = 10.1503/cmaj.1040752 | quote = Aminotransferase clearance is carried out within the liver by sinusoidal cells. The half-life in the circulation is about 47 hours for ALT, about 17 hours for total AST and, on average, 87 hours for mitochondrial AST. }}</ref> [[Aminotransferase]] is cleared by [[Liver sinusoidal endothelial cell|sinusoidal cell]]s in the liver.<ref name="Giannini pp. 367–379"/>

== Function ==
ALT catalyzes the transfer of an [[amino]] group from <small>L</small>-[[alanine]] to [[Alpha-Ketoglutaric acid|α-ketoglutarate]], the products of this reversible [[transamination]] reaction being [[pyruvate]] and <small>L</small>-[[glutamate]].<ref name="pmid19085960">{{cite journal | vauthors = Yang RZ, Park S, Reagan WJ, Goldstein R, Zhong S, Lawton M, Rajamohan F, Qian K, Liu L, Gong DW | title = Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity | journal = Hepatology | volume = 49 | issue = 2 | pages = 598–607 | date = February 2009 | pmid = 19085960 | pmc = 2917112 | doi = 10.1002/hep.22657 | url = }}</ref>

:<small>L</small>-alanine + α-ketoglutarate ⇌ pyruvate + <small>L</small>-glutamate
:[[File:Alanine transaminase.svg|class=skin-invert-image|thumb|500x500px|center]]

ALT (and all aminotransferases) require the coenzyme [[pyridoxal phosphate]], which is converted into pyridoxamine in the first phase of the reaction, when an amino acid is converted into a keto acid.<ref>{{Citation |last1=Vroon |first1=David H. |title=Aminotransferases |date=1990 |work=Clinical Methods: The History, Physical, and Laboratory Examinations |editor-last=Walker |editor-first=H. Kenneth |url=https://www.ncbi.nlm.nih.gov/books/NBK425/ |access-date=2024-07-29 |edition=3rd |place=Boston |publisher=Butterworths |isbn=978-0-409-90077-4 |pmid=21250265 |last2=Israili |first2=Zafar |editor2-last=Hall |editor2-first=W. Dallas |editor3-last=Hurst |editor3-first=J. Willis}}</ref>
{{Further|Prati criteria}}

==Clinical significance==
ALT is commonly measured clinically as part of [[liver function tests]] and is a component of the [[AST/ALT ratio]].<ref name=Statliver>{{cite journal | vauthors = Lala V, Goyal A, Bansal P, Minter D | title = Liver Function Tests | journal = Stat Pearls | date = July 2020 | pmid = 29494096 | location = Treasure Island (FL) | publisher = StatPearls Publishing }}</ref>  When used in diagnostics, it is almost always measured in international units/liter (IU/L)<ref name=Ghouri2010>{{cite journal | vauthors = Ghouri N, Preiss D, Sattar N | title = Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease: a narrative review and clinical perspective of prospective data | journal = Hepatology | volume = 52 | issue = 3 | pages = 1156–61 | date = September 2010 | pmid = 20658466 | doi = 10.1002/hep.23789 | s2cid = 5141849 | doi-access = free }}</ref> or [[Katal|μkat]].  While sources vary on specific reference range values for patients, 0-40 IU/L is the standard reference range for experimental studies.<ref name=Statliver/>

===Elevated levels===
Test results should always be interpreted using the [[reference range]] from the laboratory that produced the result. However typical reference intervals for ALT are:
{| class="wikitable"
 |-
 |'''Patient type'''||Reference ranges<ref>{{cite web | vauthors = Marshall W | title = Alanine aminotransferase: analyte monograph | url = http://www.acb.org.uk/Nat%20Lab%20Med%20Hbk/ALT.pdf | work = Association for Clinical Biochemistry and Laboratory Medicine | access-date = 7 October 2013 | date = 2012 | pages = 3–7 | archive-date = 8 August 2014 | archive-url = https://web.archive.org/web/20140808041835/http://www.acb.org.uk/Nat%20Lab%20Med%20Hbk/ALT.pdf | url-status = dead }}</ref>

|-
 | Male ||  ≤ 45 IU/L
|-
 | Female ||  ≤ 34 IU/L

|}

Significantly elevated levels of ALT (SGPT) often suggest the existence of other medical problems such as viral [[hepatitis]], [[diabetes]], [[congestive heart failure]], liver damage, [[bile duct]] problems, [[infectious mononucleosis]], or [[myopathy]], so ALT is commonly used as a way of screening for liver problems.{{citation needed|date=May 2020}} Elevated ALT may also be caused by dietary [[choline]] deficiency.{{citation needed|date=May 2020}} However, elevated levels of ALT do not automatically mean that medical problems exist. Fluctuation of ALT levels is normal over the course of the day, and they can also increase in response to strenuous physical exercise.<ref name="pmid15791889">{{cite journal | vauthors = Giboney PT | title = Mildly elevated liver transaminase levels in the asymptomatic patient | journal = American Family Physician | volume = 71 | issue = 6 | pages = 1105–10 | date = March 2005 | pmid = 15791889 | url = http://www.aafp.org/afp/20050315/1105.html }}</ref>

When elevated ALT levels are found in the blood, the possible underlying causes can be further narrowed down by measuring other enzymes. For example, elevated ALT levels due to [[hepatocyte]] damage can be distinguished from bile duct problems by measuring [[alkaline phosphatase]]. Also, myopathy-related elevations in ALT should be suspected when the aspartate transaminase (AST) is greater than ALT; the possibility of muscle disease causing elevations in liver tests can be further explored by measuring muscle enzymes, including [[creatine kinase]]. Many drugs may elevate ALT levels, including [[zileuton]], [[Omega-3-acid ethyl esters|omega−3-acid ethyl esters]] (Lovaza),<ref>{{cite journal | vauthors = Dubbeldam JL, de Jongh HJ, Osse JW | title = Pieter Dullemeijer, professor of animal morphology | journal = Acta Morphologica Neerlando-Scandinavica | volume = 27 | issue = 1–2 | pages = 9–16 | date = 2008 | pmid = 2683599 }}</ref> anti-inflammatory drugs, antibiotics, cholesterol medications, some antipsychotics such as risperidone, and anticonvulsants.<ref>{{Cite journal |last1=Bays |first1=Harold E. |last2=McKenney |first2=James |last3=Maki |first3=Kevin C. |last4=Doyle |first4=Ralph T. |last5=Carter |first5=Roderick N. |last6=Stein |first6=Evan |date=2010-02-01 |title=Effects of Prescription Omega-3-Acid Ethyl Esters on Non—High-Density Lipoprotein Cholesterol When Coadministered With Escalating Doses of Atorvastatin |journal=Mayo Clinic Proceedings |language=en |volume=85 |issue=2 |pages=122–128 |doi=10.4065/mcp.2009.0397|pmid=20118387 |pmc=2813819 }}</ref> [[Paracetamol]] (acetaminophen) may also elevate ALT levels.<ref name="pmid16820551">{{cite journal | vauthors = Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, Harris SC | title = Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial | journal = JAMA | volume = 296 | issue = 1 | pages = 87–93 | date = July 2006 | pmid = 16820551 | doi = 10.1001/jama.296.1.87 | doi-access =  }}</ref>

For years, the [[American Red Cross]] used ALT testing as part of the battery of tests to ensure the safety of its blood supply by deferring donors with elevated ALT levels. The intent was to identify donors potentially infected with hepatitis C because no specific test for that disease was available at the time. Prior to July 1992, widespread blood donation testing in the US for hepatitis C was not carried out by major blood banks. With the introduction of second-generation [[ELISA]] antibody tests for [[hepatitis C]], the Red Cross changed the ALT policy. {{As of|2003|07}}, donors previously disqualified for elevated ALT levels and no other reason may be reinstated as donors when they contact the donor-counseling department of their regional Red Cross organization.<ref>{{cite web | first = Darla | last = Van Ostrand | name-list-style = vanc | work = American Red Cross of Tompkins County |url= http://www.tompkins-redcross.org/donor_req.htm |title=Red Cross Donor Requirements |access-date=1 August 2005 |archive-url=https://web.archive.org/web/20051103142555/http://www.tompkins-redcross.org/donor_req.htm |archive-date=3 November 2005 |url-status=dead |df=dmy-all }}</ref>

In 2000, the American Association for Clinical Chemistry determined that the appropriate terminology for AST and ALT are aspartate aminotransferase and alanine aminotransferase. The term transaminase is outdated and no longer used in liver disease.<ref name=":0">{{cite journal | vauthors = Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB | title = Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests | journal = Clinical Chemistry | volume = 46 | issue = 12 | pages = 2027–49 | date = December 2000 | doi = 10.1093/clinchem/46.12.2027 | pmid = 11106349 | doi-access = free }}</ref>

=== Low ALT ===
Low plasma ALT can be a marker of low [[Skeletal muscle|muscle mass]] and is associated with [[Frailty syndrome|frailty]], [[sarcopenia]], [[disability]], as well as increased mortality in the elderly population.<ref>{{Cite journal |last1=Vespasiani-Gentilucci |first1=Umberto  |last2=De Vincentis |first2=Antonio |last3=Ferrucci |first3=Luigi |last4=Bandinelli |first4=Stefania |last5=Incalzi |first5=Raffaele Antonelli |last6=Picardi |first6=Antonio |date=2017-06-17 |url=https://academic.oup.com/biomedgerontology/article/73/7/925/3871170 |title=Low Alanine Aminotransferase Levels in the Elderly Population: Frailty, Disability, Sarcopenia, and Reduced Survival |journal=The Journals of Gerontology |volume=73 |issue=7 |pages=925–930 |doi=10.1093/gerona/glx126 |pmid=28633440 |pmc=6001897 |access-date=2024-03-24}}</ref> In patients with [[inflammatory bowel disease]], low ALT is associated with a more active disease.<ref>{{Cite journal |last1=Shafrir |first1=Asher |last2=Katz |first2=Lior H. |last3=Shauly-Aharonov |first3=Michal |last4=Zinger |first4=Adar |last5=Safadi |first5=Rifaat |last6=Stokar |first6=Joshua |last7=Kalisky |first7=Itay |date=2024-03-24 |title=Low ALT Is Associated with IBD and Disease Activity: Results from a Nationwide Study |journal=Journal of Clinical Medicine |language=en |volume=13 |issue=7 |pages=1869 |doi=10.3390/jcm13071869 |doi-access=free |pmid=38610634 |issn=2077-0383|pmc=11012492 }}</ref>

== See also ==
* [[Aspartate transaminase]]
* [[Liver function tests]]
* [[Fatty liver disease]]

== References ==
{{reflist|33em}}

== External links ==
* {{MeshName|Alanine+transaminase}}
* [http://www.acb.org.uk/Nat%20Lab%20Med%20Hbk/ALT.pdf ALT: analyte monograph; The Association for Clinical Biochemistry and Laboratory Medicine] {{Webarchive|url=https://web.archive.org/web/20140808041835/http://www.acb.org.uk/Nat%20Lab%20Med%20Hbk/ALT.pdf |date=8 August 2014 }}
* [http://labtestsonline.org/understanding/analytes/alt/tab/test Alanine aminotransferase (ALT) at Lab Tests Online]

{{Glycolysis enzymes}}
{{Amino acid metabolism enzymes}}
{{Blood tests}}
{{Nitrogenous transferases}}
{{Enzymes}}
{{Glutamate metabolism and transport modulators}}
{{Portal bar|Biology|border=no}}

{{Use dmy dates|date=April 2017}}

{{DEFAULTSORT:Alanine Transaminase}}
[[Category:Biomarkers]]
[[Category:Liver function tests]]
[[Category:Enzymes]]
[[Category:EC 2.6.1]]
[[Category:Hepatology]]
[[Category:Glutamate (neurotransmitter)]]