Alanine transaminase

Short description: Mammalian protein

Alanine transaminase

Human alanine transaminase 2 homodimer bound to PLP. PDB: 3IHJ​

Identifiers
EC number| 2.6.1.2
CAS number| 9000-86-6
Databases
IntEnz| IntEnz view
BRENDA| BRENDA entry
ExPASy| NiceZyme view
KEGG| KEGG entry
MetaCyc| metabolic pathway
PRIAM| profile
PDB structures| RCSB PDB PDBe PDBsum
Gene Ontology| AmiGO  / QuickGO
| Search

PMC| articles
PubMed| articles
NCBI| proteins

Alanine aminotransferase (ALT or ALAT), formerly alanine transaminase (ALT),[1] and even earlier referred to as serum glutamate-pyruvate transaminase (GPT) or serum glutamic-pyruvic transaminase (SGPT), is a transaminase enzyme (EC 2.6.1.2) that was first characterized in the mid-1950s by Arthur Karmen and colleagues.[2] 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.[3]

The half-life of ALT in the circulation approximates 47 hours.[4] Aminotransferase is cleared by sinusoidal cells in the liver.[4]

## Contents

* 1 Function
* 2 Clinical significance
* 2.1 Elevated levels
* 2.2 Low ALT
* 3 See also
* 4 References
* 5 External links

## 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.[5]

L-alanine + α-ketoglutarate ⇌ pyruvate + 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.[6]

## Clinical significance

ALT is commonly measured clinically as part of liver function tests and is a component of the AST/ALT ratio.[7] When used in diagnostics, it is almost always measured in international units/liter (IU/L)[8] or μkat. While sources vary on specific reference range values for patients, 0-40 IU/L is the standard reference range for experimental studies.[7]

### 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[9]

|

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.{{citation needed|date=May 2020} 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.[10]

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),[11] anti-inflammatory drugs, antibiotics, cholesterol medications, some antipsychotics such as risperidone, and anticonvulsants.[12] Paracetamol (acetaminophen) may also elevate ALT levels.[13]

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 July 2003[update], 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.[14]

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.[1]

### 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.[15] In patients with inflammatory bowel disease, low ALT is associated with a more active disease.[16]

## See also

* Aspartate transaminase
* Liver function tests
* Fatty liver disease

## References

1. ↑ 1.0 1.1 "Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests". Clinical Chemistry 46 (12): 2027–49. December 2000. doi:10.1093/clinchem/46.12.2027. PMID 11106349.
2. ↑ "Transaminase activity in human blood". The Journal of Clinical Investigation 34 (1): 126–31. January 1955. doi:10.1172/JCI103055. PMID 13221663.
3. ↑ 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. doi:10.5114/amsad.2020.103028. ISSN 2451-0629. PMID 33644486. PMC 7885810. https://amsad.termedia.pl/The-significance-of-transaminase-ratio-AST-ALT-in-acute-myocardial-infarction,125739,0,2.html.
4. ↑ 4.0 4.1 "Liver enzyme alteration: a guide for clinicians". Canadian Medical Association Journal 172 (3): 367–79. February 2005. doi:10.1503/cmaj.1040752. PMID 15684121. "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.".
5. ↑ "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. doi:10.1002/hep.22657. PMID 19085960.
6. ↑ Vroon, David H.; Israili, Zafar (1990), Walker, H. Kenneth; Hall, W. Dallas; Hurst, J. Willis, eds., "Aminotransferases", Clinical Methods: The History, Physical, and Laboratory Examinations (Boston: Butterworths), ISBN 978-0-409-90077-4, PMID 21250265, https://www.ncbi.nlm.nih.gov/books/NBK425/, retrieved 2024-07-29
7. ↑ 7.0 7.1 "Liver Function Tests". Stat Pearls (Treasure Island (FL): StatPearls Publishing). July 2020. PMID 29494096.
8. ↑ "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. doi:10.1002/hep.23789. PMID 20658466.
9. ↑ "Alanine aminotransferase: analyte monograph". Association for Clinical Biochemistry and Laboratory Medicine. 2012. pp. 3–7. http://www.acb.org.uk/Nat Lab Med Hbk/ALT.pdf.
10. ↑ "Mildly elevated liver transaminase levels in the asymptomatic patient". American Family Physician 71 (6): 1105–10. March 2005. PMID 15791889. http://www.aafp.org/afp/20050315/1105.html.
11. ↑ "Pieter Dullemeijer, professor of animal morphology". Acta Morphologica Neerlando-Scandinavica 27 (1–2): 9–16. 2008. PMID 2683599.
12. ↑ 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" (in en). Mayo Clinic Proceedings 85 (2): 122–128. doi:10.4065/mcp.2009.0397. PMID 20118387.
13. ↑ "Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial". JAMA 296 (1): 87–93. July 2006. doi:10.1001/jama.296.1.87. PMID 16820551.
14. ↑ Van Ostrand, Darla. "Red Cross Donor Requirements". American Red Cross of Tompkins County. http://www.tompkins-redcross.org/donor_req.htm.
15. ↑ 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. doi:10.1093/gerona/glx126. PMID 28633440. PMC 6001897. https://academic.oup.com/biomedgerontology/article/73/7/925/3871170. Retrieved 2024-03-24.
16. ↑ 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" (in en). Journal of Clinical Medicine 13 (7): 1869. doi:10.3390/jcm13071869. ISSN 2077-0383. PMID 38610634.

## External links

* Alanine+transaminase at the US National Library of Medicine Medical Subject Headings (MeSH)
* ALT: analyte monograph; The Association for Clinical Biochemistry and Laboratory Medicine
* Alanine aminotransferase (ALT) at Lab Tests Online

{{Navbox

| name = Glycolysis enzymes
| title = Metabolism: carbohydrate metabolism: [[Biology:Glycoglycolysis/gluconeogenesis enzymes
| state = autocollapse
| listclass = hlist

| group1 = Glycolysis

| list1 =

* Hexokinase (HK1, HK2, HK3, Glucokinase)→/Glucose 6-phosphatase←
* Glucose isomerase
* Phosphofructokinase 1 (Liver, Muscle, Platelet)→/Fructose 1,6-bisphosphatase←

* Fructose-bisphosphate aldolase (Aldolase A, B, C)
* Triosephosphate isomerase

* Glyceraldehyde 3-phosphate dehydrogenase
* Phosphoglycerate kinase
* Phosphoglycerate mutase
* Enolase
* Pyruvate kinase (PKLR, PKM2)

| group2 = Gluconeogenesis only

| list2 =

to oxaloacetate:|

* Pyruvate carboxylase
* Phosphoenolpyruvate carboxykinase

|

from lactate (Cori cycle):|

* Lactate dehydrogenase

from alanine (Alanine cycle):|

* Alanine transaminase

from glycerol:|

* Glycerol kinase
* Glycerol dehydrogenase

| group4 = Regulatory
| list4 =

* fructose 2,6-bisphosphatase
* PFKFB1, PFKFB2, PFKFB3, PFKFB4
* Bisphosphoglycerate mutase

* v
* t
* e

Metabolism: Protein metabolism, synthesis and catabolism enzymes

Essential amino acids are in Capitals

K→acetyl-CoA|

| LYSINE→|

* Saccharopine dehydrogenase
* Glutaryl-CoA dehydrogenase

|

LEUCINE→|

* 3-Hydroxybutyryl-CoA dehydrogenase
* Branched-chain amino acid aminotransferase
* Branched-chain alpha-keto acid dehydrogenase complex
* Enoyl-CoA hydratase
* HMG-CoA lyase
* HMG-CoA reductase
* Isovaleryl coenzyme A dehydrogenase
* α-Ketoisocaproate dioxygenase
* Leucine 2,3-aminomutase
* Methylcrotonyl-CoA carboxylase
* Methylglutaconyl-CoA hydratase

(See Template:Leucine metabolism in humans – this diagram does not include the pathway for β-leucine synthesis via leucine 2,3-aminomutase)

TRYPTOPHAN→|

* Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase
* Arylformamidase
* Kynureninase
* 3-hydroxyanthranilate oxidase
* Aminocarboxymuconate-semialdehyde decarboxylase
* Aminomuconate-semialdehyde dehydrogenase

PHENYLALANINE→tyrosine→|

* (see below)

| G→pyruvate
→citrate|

| glycine→serine→|

* Serine hydroxymethyltransferase
* Serine dehydratase

* glycine→creatine: Guanidinoacetate N-methyltransferase
* Creatine kinase

|

alanine→|

* Alanine transaminase

cysteine→|

* D-cysteine desulfhydrase

threonine→|

* L-threonine dehydrogenase

G→glutamate→
α-ketoglutarate|

| HISTIDINE→|

* Histidine ammonia-lyase
* Urocanate hydratase
* Formiminotransferase cyclodeaminase

|

proline→|

* Proline oxidase
* Pyrroline-5-carboxylate reductase
* 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1
* PYCR1

arginine→|

* Ornithine aminotransferase
* Ornithine decarboxylase
* Agmatinase

→alpha-ketoglutarate→TCA|

* Glutamate dehydrogenase

Other|

* cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase
* Glutathione synthetase
* Gamma-glutamyl transpeptidase

* glutamate→glutamine: Glutamine synthetase
* Glutaminase

G→propionyl-CoA→
succinyl-CoA|

| VALINE→|

* Branched-chain amino acid aminotransferase
* Branched-chain alpha-keto acid dehydrogenase complex
* Enoyl-CoA hydratase
* 3-hydroxyisobutyryl-CoA hydrolase
* 3-hydroxyisobutyrate dehydrogenase
* Methylmalonate semialdehyde dehydrogenase

|

ISOLEUCINE→|

* Branched-chain amino acid aminotransferase
* Branched-chain alpha-keto acid dehydrogenase complex
* 3-hydroxy-2-methylbutyryl-CoA dehydrogenase

METHIONINE→|

* generation of homocysteine: Methionine adenosyltransferase
* Adenosylhomocysteinase

* regeneration of methionine: Methionine synthase/Homocysteine methyltransferase
* Betaine-homocysteine methyltransferase

* conversion to cysteine: Cystathionine beta synthase
* Cystathionine gamma-lyase

THREONINE→|

* Threonine aldolase

→succinyl-CoA→TCA|

* Propionyl-CoA carboxylase
* Methylmalonyl CoA epimerase
* Methylmalonyl-CoA mutase

G→fumarate|

| PHENYLALANINE→tyrosine→|

* Phenylalanine hydroxylase
* Tyrosine aminotransferase
* 4-Hydroxyphenylpyruvate dioxygenase
* Homogentisate 1,2-dioxygenase
* Fumarylacetoacetate hydrolase

* tyrosine→melanin: Tyrosinase

|

G→oxaloacetate|

| asparagine→aspartate→|

* Asparaginase/Asparagine synthetase
* Aspartate transaminase

|

* v
* t
* e

Common for blood tests (CPT 82000–84999)

Electrolytes|

* Sodium
* Potassium
* Chloride
* Calcium
* Renal function
* Creatinine
* Urea
* BUN-to-creatinine ratio
* Plasma osmolality
* Serum osmolal gap

Acid-base|

* Anion gap
* Arterial blood gas
* Base excess
* Bicarbonate
* CO2 content

Iron tests|

* Ferritin
* Serum iron
* Transferrin saturation
* Total iron-binding capacity
* Transferrin
* Transferrin receptor

Hormones|

* ACTH stimulation test
* Thyroid function tests
* Thyroid-stimulating hormone

Metabolism|

* Blood lipids

Cardiovascular|

* Cardiac marker
* Troponin test
* CPK-MB test
* Lactate dehydrogenase
* Myoglobin
* Glycogen phosphorylase isoenzyme BB

Liver function tests|

* Proteins
* Human serum albumin
* Serum total protein
* ALP
* transaminases
* ALT
* AST
* AST/ALT ratio
* Bilirubin
* Unconjugated
* Conjugated

Pancreas|

* Amylase
* Lipase
* Pancreatic lipase

* v
* t
* e

Transferase: nitrogenous groups (EC 2.6)

2.6.1: Transaminases|

* Aspartate transaminase
* GOT1
* GOT2
* Alanine transaminase
* GABA transaminase
* Tyrosine aminotransferase
* Kynurenine—oxoglutarate transaminase
* Ornithine aminotransferase
* Branched-chain amino acid aminotransferase
* Alanine—glyoxylate transaminase
* AGXT

2.6.3: Oximinotransferases|

* Oximinotransferase

2.6.99: Other|

* Pyridoxine 5'-phosphate synthase

* v
* t
* e

Enzymes

Activity|

* Active site
* Binding site
* Catalytic triad
* Oxyanion hole
* Enzyme promiscuity
* Catalytically perfect enzyme
* Coenzyme
* Cofactor
* Enzyme catalysis

Regulation|

* Allosteric regulation
* Cooperativity
* Enzyme inhibitor
* Enzyme activator

Classification|

* EC number
* Enzyme superfamily
* Enzyme family
* List of enzymes

Kinetics|

* Enzyme kinetics
* Eadie–Hofstee diagram
* Hanes–Woolf plot
* Lineweaver–Burk plot
* Michaelis–Menten kinetics

Types|

* EC1 Oxidoreductases (list)
* EC2 Transferases (list)
* EC3 Hydrolases (list)
* EC4 Lyases (list)
* EC5 Isomerases (list)
* EC6 Ligases (list)
* EC7 Translocases (list)

* v
* t
* e

Glutamate metabolism and transport modulators

Transporter|

| EAATs|

* Amphetamine
* Aspartic acid (aspartate)
* cis-ACBD
* DHKA
* Glutamic acid (glutamate)
* HIP-A
* HIP-B
* Kainic acid
* L-(-)-threo-3-Hydroxyaspartic acid
* L-αAA
* L-CCG-III ((2S,3S,4R)-CCG)
* L-Serine-O-sulphate (SOS)
* L-trans-2,4-PDC
* MPDC
* Maslinic acid
* SYM-2081
* TBOA
* TFB-TBOA
* Theanine
* threo-3-Methylglutamic acid
* UCPH-101
* WAY-213,613

|

vGluTs|

* 4-Methylene-L-glutamate
* 6-(4'-Phenylstyryl)-QDC
* 6-Biphenyl-4-yl-QDC
* 7-CKA
* Acid red 114
* Amido black 10B (naphthol blue black)
* Bafilomycin A1
* Benzopurpurin 4B
* Bumetamide
* Chicago sky blue 6B
* Aspartic acid (aspartate)
* DIDS
* Direct blue 71
* Erythro-4-methyl-L-glutamic acid
* Evans blue
* Furosemide
* Glutamic acid (glutamate)
* Kynurenic acid
* Nigericin
* NPPB (N144)
* Ponceau SS
* Reactive blue 2
* Rose bengal
* SITS
* trans-ACDP
* Trypan blue
* Valinomycin
* Xanthurenic acid

Enzyme|

| GAH|

* BPTES
* CB-839
* DON

|

AST|

* 2-Amino-3-butenoic acid
* AAOA
* AMB
* β-DL-Methylene-aspartate
* Hydrazinosuccinate

ALT|

* β-Chloro-L-alanine
* L-Cycloserine
* Propargylglycine

GDH|

* AAOA
* Bithionol
* Chloroquine
* EGCG
* GTP
* GW5074
* Hexachlorophene
* Hydroxylamine
* Palmitoyl-CoA
* Pyridoxal phosphate

GS|

* 2-Aminoadipic acid
* JFD01307SC
* Methionine sulfoximine
* Phosphinothricin (glufosinate)

GAD|

* 3-Mercaptopropionic acid
* AAOA
* L-Allylglycine
* Semicarbazide

See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Metabotropic glutamate receptor modulators • GABA metabolism and transport modulators

0.00

(0 votes)

Original source: https://en.wikipedia.org/wiki/Alanine transaminase. Read more

|

Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Alanine_transaminase&oldid=4016699"
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[EAATs]: Excitatory amino acid transporters
*[vGluTs]: Vesicular glutamate transporters
*[GAH]: Glutamine aminohydrolase (glutaminase)
*[AST]: Aspartate aminotransferase
*[ALT]: Alanine aminotransferase
*[GDH]: Glutamate dehydrogenase
*[GS]: Glutamine synthetase
*[GAD]: Glutamate decarboxylase