Alanine transaminase explained

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Go Code:0004021
Alanine transaminase

Alanine transaminase (ALT), also known as alanine aminotransferase (ALT or ALAT), formerly serum glutamate-pyruvate transaminase (GPT) or serum glutamic-pyruvic transaminase (SGPT), is a transaminase enzyme that was first characterized in the mid-1950s by Arthur Karmen and colleagues.[1] ALT is found in 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 biomarkers for liver health.[2]

The half-life of ALT in the circulation approximates 47 hours.[3] Aminotransferase is cleared by sinusoidal cells in the liver.[3]

Function

ALT catalyzes the transfer of an amino group from L-alanine to α-ketoglutarate, the products of this reversible transamination reaction being pyruvate and L-glutamate.[4]

L-alanine + α-ketoglutaratepyruvate + L-glutamate

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.

Clinical significance

ALT is commonly measured clinically as part of liver function tests and is a component of the AST/ALT ratio.[5] When used in diagnostics, it is almost always measured in international units/liter (IU/L)[6] or μkat. While sources vary on specific reference range values for patients, 0-40 IU/L is the standard reference range for experimental studies.[5]

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:

- Patient typeReference ranges[7]
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. Elevated ALT may also be caused by dietary choline deficiency. 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.[8]

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 (Lovaza),[9] anti-inflammatory drugs, antibiotics, cholesterol medications, some antipsychotics such as risperidone, and anticonvulsants.[10] Paracetamol (acetaminophen) may also elevate ALT levels.[11]

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., 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.[12]

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.[13]

Low ALT

Low plasma ALT can be a marker of low muscle mass and is associated with frailty, sarcopenia, disability, as well as increased mortality in the elderly population.[14] In patients with inflammatory bowel disease, low ALT is associated with a more active disease.[15]

See also

External links

Notes and References

  1. Karmen A, Wroblewski F, Ladue JS . Transaminase activity in human blood . The Journal of Clinical Investigation . 34 . 1 . 126–31 . January 1955 . 13221663 . 438594 . 10.1172/JCI103055 .
  2. Djakpo . Dodji Kossi . Wang . Zhi Quan . Shrestha . Merina . 2020-12-26 . The significance of transaminase ratio (AST/ALT) in acute myocardial infarction . Archives of Medical Science – Atherosclerotic Diseases . 5 . 1 . 279–283 . 10.5114/amsad.2020.103028 . 2451-0629. 7885810 .
  3. Giannini EG, Testa R, Savarino V . Liver enzyme alteration: a guide for clinicians . Canadian Medical Association Journal . 172 . 3 . 367–79 . February 2005 . 15684121 . 545762 . 10.1503/cmaj.1040752 . 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. .
  4. Yang RZ, Park S, Reagan WJ, Goldstein R, Zhong S, Lawton M, Rajamohan F, Qian K, Liu L, Gong DW . Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity . Hepatology . 49 . 2 . 598–607 . February 2009 . 19085960 . 2917112 . 10.1002/hep.22657 .
  5. Lala V, Goyal A, Bansal P, Minter D . Liver Function Tests . Stat Pearls . July 2020 . 29494096 . Treasure Island (FL) . StatPearls Publishing .
  6. Ghouri N, Preiss D, Sattar N . Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease: a narrative review and clinical perspective of prospective data . Hepatology . 52 . 3 . 1156–61 . September 2010 . 20658466 . 10.1002/hep.23789 . 5141849 . free .
  7. Web site: Marshall W . Alanine aminotransferase: analyte monograph . Association for Clinical Biochemistry and Laboratory Medicine . 7 October 2013 . 2012 . 3–7 . 8 August 2014 . https://web.archive.org/web/20140808041835/http://www.acb.org.uk/Nat%20Lab%20Med%20Hbk/ALT.pdf . dead .
  8. Giboney PT . Mildly elevated liver transaminase levels in the asymptomatic patient . American Family Physician . 71 . 6 . 1105–10 . March 2005 . 15791889 .
  9. Dubbeldam JL, de Jongh HJ, Osse JW . Pieter Dullemeijer, professor of animal morphology . Acta Morphologica Neerlando-Scandinavica . 27 . 1–2 . 9–16 . 2008 . 2683599 .
  10. Bays . Harold E. . McKenney . James . Maki . Kevin C. . Doyle . Ralph T. . Carter . Roderick N. . Stein . Evan . 2010-02-01 . Effects of Prescription Omega-3-Acid Ethyl Esters on Non—High-Density Lipoprotein Cholesterol When Coadministered With Escalating Doses of Atorvastatin . Mayo Clinic Proceedings . en . 85 . 2 . 122–128 . 10.4065/mcp.2009.0397. 2813819 .
  11. Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, Harris SC . Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial . JAMA . 296 . 1 . 87–93 . July 2006 . 16820551 . 10.1001/jama.296.1.87 .
  12. Web site: Darla . Van Ostrand . vanc . American Red Cross of Tompkins County . Red Cross Donor Requirements . 1 August 2005 . https://web.archive.org/web/20051103142555/http://www.tompkins-redcross.org/donor_req.htm . 3 November 2005 . dead . dmy-all .
  13. Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB . Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests . Clinical Chemistry . 46 . 12 . 2027–49 . December 2000 . 10.1093/clinchem/46.12.2027 . 11106349 . free .
  14. Vespasiani-Gentilucci . Umberto . De Vincentis . Antonio . Ferrucci . Luigi . Bandinelli . Stefania . Incalzi . Raffaele Antonelli . Picardi . Antonio . 2017-06-17 . Low Alanine Aminotransferase Levels in the Elderly Population: Frailty, Disability, Sarcopenia, and Reduced Survival . The Journals of Gerontology . 73 . 7 . 925–930 . 10.1093/gerona/glx126 . 28633440 . 6001897 . 2024-03-24.
  15. Shafrir . Asher . Katz . Lior H. . Shauly-Aharonov . Michal . Zinger . Adar . Safadi . Rifaat . Stokar . Joshua . Kalisky . Itay . 2024-03-24 . Low ALT Is Associated with IBD and Disease Activity: Results from a Nationwide Study . Journal of Clinical Medicine . en . 13 . 7 . 1869 . 10.3390/jcm13071869 . free . 2077-0383. 11012492 .