Alanine transaminase: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
(consistent citation formatting)
Line 29: Line 29:
}}
}}


'''Alanine transaminase''' ('''ALT''') is a [[transaminase]] [[enzyme]] ({{EC number|2.6.1.2}}).  It is also called '''alanine aminotransferase''' ('''ALAT''') and was formerly called serum glutamate-pyruvate transaminase (SGPT) or serum glutamic-pyruvic transaminase (SGPT) and 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 = Jan 1955 | pmid = 13221663 | doi = 10.1172/JCI103055 | pmc=438594}}</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 commonly measured clinically as [[biomarker]]s for liver health. The tests are part of [[blood test|blood panels]].
'''Alanine transaminase''' ('''ALT''') is a [[transaminase]] [[enzyme]] ({{EC number|2.6.1.2}}).  It is also called '''alanine aminotransferase''' ('''ALAT''') and was formerly called serum glutamate-pyruvate transaminase (SGPT) or serum glutamic-pyruvic transaminase (SGPT) and 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 commonly measured clinically as [[biomarker]]s for liver health. The tests are part of [[blood test|blood panels]].


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


:[[glutamate|L-glutamate]] + [[pyruvate]] &#8652; [[alpha-ketoglutaric acid|α-ketoglutarate]] + [[alanine|L-alanine]]
:[[alanine|L-alanine]] + [[alpha-ketoglutaric acid|α-ketoglutarate]] &#8652; [[pyruvate]] + [[glutamate|L-glutamate]]
[[Image:Alanine amino transférase.png|thumb|none|600px|Alanine transaminase]]
[[File:Alanine transaminase.png|thumb|none|600px]]


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.
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==
==Clinical significance==
ALT is commonly measured clinically as a part of a diagnostic evaluation of [[Liver function tests|hepatocellular injury]], to determine liver health.  When used in diagnostics, it is almost always measured in international units/liter (IU/L)<ref name=Wang2012>{{cite journal | vauthors = Wang CS, Chang TT, Yao WJ, Wang ST, Chou P | title = Impact of increasing alanine aminotransferase levels within normal range on incident diabetes | journal = Journal of the Formosan Medical Association = Taiwan Yi Zhi | volume = 111 | issue = 4 | pages = 201–8 | date = April 2012 | pmid = 22526208 | doi = 10.1016/j.jfma.2011.04.004 }}</ref><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 }}</ref> or µkat.  While sources vary on specific reference range values for patients, 10-40 IU/L is the standard reference range for experimental studies.<ref name=Wang2012 /> Alanine transaminase shows a marked [[diurnal variation]].{{citation needed|date=June 2013}}
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, Minter DA | title = Liver Function Tests | journal = Stat Pearls | date = January 2018 | pmid = 29494096 }}</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 }}</ref> or 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/>
 
The [[AST/ALT ratio|ratio of ALT to AST (aspartate aminotransferase)]] also has clinical significance.


===Elevated levels===
===Elevated levels===
Line 48: Line 46:
{| class="wikitable"
{| class="wikitable"
  |-
  |-
  |'''Patient type'''||Reference ranges<ref>{{cite web|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|accessdate=7 October 2013}}</ref>   
  |'''Patient type'''||Reference ranges<ref>{{cite web|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}}</ref>   
  |-
  |-
  | Female ||  ≤ 34 IU/L
  | Female ||  ≤ 34 IU/L
  |-
  |-
  | Male ||  ≤ 52 IU/L
  | Male ||  ≤ 45 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.<ref>Paul T. Giboney M.D., [http://www.aafp.org/afp/20050315/1105.html Mildly Elevated Liver Transaminase Levels in the Asymptomatic Patient], ''American Family Physician''.</ref>
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.<ref>Paul T. Giboney M.D., [http://www.aafp.org/afp/20050315/1105.html Mildly Elevated Liver Transaminase Levels in the Asymptomatic Patient], ''American Family Physician''.</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 ([[Lovaza]]),<ref>{{cite journal | pmc = 2683599 | title = Omega-3-acid Ethyl Esters (Lovaza) For Severe Hypertriglyceridemia | journal = Pharmacy and Therapeutics | date = 2008 | volume = 33 | issue = 5 | pages = 271–303 | vauthors = Koski RR }}</ref> anti-inflammatory drugs, antibiotics, cholesterol medications, some antipsychotics such as risperidone, and anticonvulsants.{{Citation needed|date=August 2011}}.  [[Paracetamol]] (also known as 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 }}</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 ([[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 | pmc = 2683599 }}</ref> anti-inflammatory drugs, antibiotics, cholesterol medications, some antipsychotics such as risperidone, and anticonvulsants.{{Citation needed|date=August 2011}} [[Paracetamol]] (also known as 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 }}</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 USA 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 by contacting the donor-counseling department of their regional Red Cross organization.<ref>[http://www.tompkins-redcross.org/donor_req.htm Red Cross Donor Requirements]</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 USA 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 by contacting the donor-counseling department of their regional Red Cross organization.<ref>{{Cite web |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 |dead-url=yes |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>Clin Chem 2000;46:2027-2049</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>Clin Chem 2000;46:2027-2049</ref>

Revision as of 20:06, 22 November 2018

glutamic-pyruvate transaminase1
Identifiers
SymbolGPT
Entrez2875
HUGO4552
OMIM138200
RefSeqNM_005309
UniProtP24298
Other data
EC number2.6.1.2
LocusChr. 8 q24.2-qter
Alanine transaminase
Identifiers
EC number2.6.1.2
CAS number9000-86-6
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

Alanine transaminase (ALT) is a transaminase enzyme (EC 2.6.1.2). It is also called alanine aminotransferase (ALAT) and was formerly called serum glutamate-pyruvate transaminase (SGPT) or serum glutamic-pyruvic transaminase (SGPT) and 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 commonly measured clinically as biomarkers for liver health. The tests are part of blood panels.

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.

L-alanine + α-ketoglutarate ⇌ pyruvate + L-glutamate
File:Alanine transaminase.png

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.[2] When used in diagnostics, it is almost always measured in international units/liter (IU/L)[3] or µkat. While sources vary on specific reference range values for patients, 0-40 IU/L is the standard reference range for experimental studies.[2]

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 type Reference ranges[4]
Female ≤ 34 IU/L
Male ≤ 45 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.[5]

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),[6] anti-inflammatory drugs, antibiotics, cholesterol medications, some antipsychotics such as risperidone, and anticonvulsants.[citation needed] Paracetamol (also known as acetaminophen) may also elevate ALT levels.[7]

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 USA 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 July 2003, donors previously disqualified for elevated ALT levels and no other reason may be reinstated as donors by contacting the donor-counseling department of their regional Red Cross organization.[8]

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.[9]

See also

References

  1. ↑ Karmen A, Wroblewski F, Ladue JS (January 1955). "Transaminase activity in human blood". The Journal of Clinical Investigation. 34 (1): 126–31. doi:10.1172/JCI103055. PMC 438594. PMID 13221663.
  2. ↑ 2.0 2.1 Lala V, Minter DA (January 2018). "Liver Function Tests". Stat Pearls. PMID 29494096.
  3. ↑ Ghouri N, Preiss D, Sattar N (September 2010). "Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease: a narrative review and clinical perspective of prospective data". Hepatology. 52 (3): 1156–61. doi:10.1002/hep.23789. PMID 20658466.
  4. ↑ "Alanine aminotransferase: analyte monograph" (PDF). Association for Clinical Biochemistry and Laboratory Medicine. Retrieved 7 October 2013.
  5. ↑ Paul T. Giboney M.D., Mildly Elevated Liver Transaminase Levels in the Asymptomatic Patient, American Family Physician.
  6. ↑ Dubbeldam JL, de Jongh HJ, Osse JW (2008). "Pieter Dullemeijer, professor of animal morphology". Acta Morphologica Neerlando-Scandinavica. 27 (1–2): 9–16. PMC 2683599.
  7. ↑ Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, Harris SC (July 2006). "Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial". Jama. 296 (1): 87–93. doi:10.1001/jama.296.1.87. PMID 16820551.
  8. ↑ "Red Cross Donor Requirements". Archived from the original on 3 November 2005. Retrieved 1 August 2005.
  9. ↑ Clin Chem 2000;46:2027-2049

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Alanine_transaminase&oldid=1523468"