Alanine transaminase

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Alanine transaminase
Human alanine transaminase 2 PDB 3IHJ.png
Human alanine transaminase 2 homodimer bound to PLP. PDB: 3IHJ
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EC no. 2.6.1.2
CAS no. 9000-86-6
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Alanine transaminase (ALT) is a transaminase enzyme (EC 2.6.1.2). It is also called alanine aminotransferase (ALT or ALAT) and was formerly called serum glutamate-pyruvate transaminase 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 routinely measured clinically as biomarkers for liver health.[ citation needed ]

Contents

The half-life of ALT in the circulation approximates 47 hours. [2] Aminotransferase is cleared by sinusoidal cells in the liver. [2]

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. [3]

L-alanine + α-ketoglutaratepyruvate + L-glutamate
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.[ citation needed ]

Clinical significance

ALT is commonly measured clinically as part of liver function tests and is a component of the AST/ALT ratio. [4] When used in diagnostics, it is almost always measured in international units/liter (IU/L) [5] or μkat. While sources vary on specific reference range values for patients, 0-40 IU/L is the standard reference range for experimental studies. [4]

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 [6]
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 ] Elevated ALT may also be caused by dietary choline deficiency.[ citation needed ] 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. [7]

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

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, 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. [10]

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. [11]

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. [12] In patients with inflammatory bowel disease, low ALT is associated with a more active disease. [13]

See also

Related Research Articles

<span class="mw-page-title-main">Alanine</span> Α-amino acid that is used in the biosynthesis of proteins

Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side chain. Consequently it is classified as a nonpolar, aliphatic α-amino acid. Under biological conditions, it exists in its zwitterionic form with its amine group protonated (as −NH3+) and its carboxyl group deprotonated (as −CO2). It is non-essential to humans as it can be synthesized metabolically and does not need to be present in the diet. It is encoded by all codons starting with GC (GCU, GCC, GCA, and GCG).

<span class="mw-page-title-main">Clinical chemistry</span> Area of clinical pathology that is generally concerned with analysis of bodily fluids

Clinical chemistry is a division in medical laboratory sciences focusing on qualitative tests of important compounds, referred to as analytes or markers, in bodily fluids and tissues using analytical techniques and specialized instruments. This interdisciplinary field includes knowledge from medicine, biology, chemistry, biomedical engineering, informatics, and an applied form of biochemistry.

<span class="mw-page-title-main">Jaundice</span> Abnormal pigmentation symptom for disease of the liver

Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. The prevalence of jaundice in adults is rare, while jaundice in babies is common, with an estimated 80% affected during their first week of life. The most commonly associated symptoms of jaundice are itchiness, pale feces, and dark urine.

Liver function tests, also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin time (aPTT), albumin, bilirubin, and others. The liver transaminases aspartate transaminase and alanine transaminase are useful biomarkers of liver injury in a patient with some degree of intact liver function.

<span class="mw-page-title-main">Alcoholic liver disease</span> Medical condition

Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.

<span class="mw-page-title-main">Alcoholic hepatitis</span> Medical condition

Alcoholic hepatitis is hepatitis due to excessive intake of alcohol. Patients typically have a history of at least 10 years of heavy alcohol intake, typically 8–10 drinks per day. It is usually found in association with fatty liver, an early stage of alcoholic liver disease, and may contribute to the progression of fibrosis, leading to cirrhosis. Symptoms may present acutely after a large amount of alcoholic intake in a short time period, or after years of excess alcohol intake. Signs and symptoms of alcoholic hepatitis include jaundice, ascites, fatigue and hepatic encephalopathy. Mild cases are self-limiting, but severe cases have a high risk of death. Severity in alcoholic hepatitis is determined several clinical prediction models such as the Maddrey's Discriminant Function and the MELD score.

<span class="mw-page-title-main">Aspartate transaminase</span> Enzyme involved in amino acid metabolism

Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or (serum) glutamic oxaloacetic transaminase, is a pyridoxal phosphate (PLP)-dependent transaminase enzyme that was first described by Arthur Karmen and colleagues in 1954. AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in amino acid metabolism. AST is found in the liver, heart, skeletal muscle, kidneys, brain, red blood cells and gall bladder. Serum AST level, serum ALT level, and their ratio are commonly measured clinically as biomarkers for liver health. The tests are part of blood panels.

<span class="mw-page-title-main">Transaminase</span> Class of enzymes

Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins.

<span class="mw-page-title-main">Cahill cycle</span> Metabolic pathway for transport of energy into and removal of ammonia from muscles

The Cahill cycle, also known as the alanine cycle or glucose-alanine cycle, is the series of reactions in which amino groups and carbons from muscle are transported to the liver. It is quite similar to the Cori cycle in the cycling of nutrients between skeletal muscle and the liver. When muscles degrade amino acids for energy needs, the resulting nitrogen is transaminated to pyruvate to form alanine. This is performed by the enzyme alanine transaminase (ALT), which converts L-glutamate and pyruvate into α-ketoglutarate and L-alanine. The resulting L-alanine is shuttled to the liver where the nitrogen enters the urea cycle and the pyruvate is used to make glucose.

Carbohydrate-deficient transferrin is a laboratory test used to help detect heavy ethanol consumption.

In medicine, the presence of elevated transaminases, commonly the transaminases alanine transaminase (ALT) and aspartate transaminase (AST), may be an indicator of liver dysfunction. Other terms include transaminasemia, transaminitis, and elevatedliver enzymes. Normal ranges for both ALT and AST vary by gender, age, and geography and are roughly 8-40 U/L. Mild transaminesemia refers to levels up to 250 U/L. Drug-induced increases such as that found with the use of anti-tuberculosis agents such as isoniazid are limited typically to below 100 U/L for either ALT or AST. Muscle sources of the enzymes, such as intense exercise, are unrelated to liver function and can markedly increase AST and ALT. Cirrhosis of the liver or fulminant liver failure secondary to hepatitis commonly reach values for both ALT and AST in the >1000 U/L range; however, many people with liver disease have normal transaminases. Elevated transaminases that persist less than six months are termed "acute" in nature, and those values that persist for six months or more are termed "chronic" in nature.

<span class="mw-page-title-main">4-aminobutyrate transaminase</span> Class of enzymes

In enzymology, 4-aminobutyrate transaminase, also called GABA transaminase or 4-aminobutyrate aminotransferase, or GABA-T, is an enzyme that catalyzes the chemical reaction:

<span class="mw-page-title-main">Alanine—glyoxylate transaminase</span>

In enzymology, an alanine-glyoxylate transaminase is an enzyme that catalyzes the chemical reaction

In enzymology, a D-amino-acid transaminase is an enzyme that catalyzes the chemical reaction:

<span class="mw-page-title-main">GOT2</span> Mitochondrial enzyme involved in amino acid metabolism

Aspartate aminotransferase, mitochondrial is an enzyme that in humans is encoded by the GOT2 gene. Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and inner-membrane mitochondrial forms, GOT1 and GOT2, respectively. GOT plays a role in amino acid metabolism and the urea and Kreb's cycle. Also, GOT2 is a major participant in the malate-aspartate shuttle, which is a passage from the cytosol to the mitochondria. The two enzymes are homodimeric and show close homology. GOT2 has been seen to have a role in cell proliferation, especially in terms of tumor growth.

<span class="mw-page-title-main">GOT1</span> Cytoplasmic enzyme involved in amino acid metabolism

Aspartate aminotransferase, cytoplasmic is an enzyme that in humans is encoded by the GOT1 gene.

Glutaminolysis (glutamine + -lysis) is a series of biochemical reactions by which the amino acid glutamine is lysed to glutamate, aspartate, CO2, pyruvate, lactate, alanine and citrate.

The AST/ALT ratio or De Ritis ratio is the ratio between the concentrations of two enzymes, aspartate transaminase (AST) and alanine transaminase, aka alanine aminotransferase (ALT), in the blood of a human or animal. It is used as one of several liver function tests, and measured with a blood test. It is sometimes useful in medical diagnosis for elevated transaminases to differentiate between causes of liver damage, or hepatotoxicity.

Dicarboxylic aminoaciduria is a rare form of aminoaciduria which is an autosomal recessive disorder of urinary glutamate and aspartate due to genetic errors related to transport of these amino acids. Mutations resulting in a lack of expression of the SLC1A1 gene, a member of the solute carrier family, are found to cause development of dicarboxylic aminoaciduria in humans. SLC1A1 encodes for EAAT3 which is found in the neurons, intestine, kidney, lung, and heart. EAAT3 is part of a family of high affinity glutamate transporters which transport both glutamate and aspartate across the plasma membrane.

Hepatic artery thrombosis occurs when a blood clot forms in the artery that provides blood flow to the liver. Hepatic artery thrombosis may occur as a complication after liver transplantation, and represents the most common complication of liver transplantation. Smoking tobacco increases the risk of hepatic artery thrombosis in people who have undergone liver transplantation.

References

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  2. 1 2 Giannini EG, Testa R, Savarino V (February 2005). "Liver enzyme alteration: a guide for clinicians". Canadian Medical Association Journal. 172 (3): 367–79. doi:10.1503/cmaj.1040752. PMC   545762 . 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.
  3. Yang RZ, Park S, Reagan WJ, Goldstein R, Zhong S, Lawton M, Rajamohan F, Qian K, Liu L, Gong DW (February 2009). "Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity". Hepatology (Baltimore, Md.). 49 (2): 598–607. doi:10.1002/hep.22657. PMC   2917112 . PMID   19085960.
  4. 1 2 Lala V, Goyal A, Bansal P, Minter D (July 2020). "Liver Function Tests". Stat Pearls. Treasure Island (FL): StatPearls Publishing. PMID   29494096.
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  6. Marshall W (2012). "Alanine aminotransferase: analyte monograph" (PDF). Association for Clinical Biochemistry and Laboratory Medicine. pp. 3–7. Archived from the original (PDF) on 8 August 2014. Retrieved 7 October 2013.
  7. Giboney PT (March 2005). "Mildly elevated liver transaminase levels in the asymptomatic patient". American Family Physician. 71 (6): 1105–10. PMID   15791889.
  8. Dubbeldam JL, de Jongh HJ, Osse JW (2008). "Pieter Dullemeijer, professor of animal morphology". Acta Morphologica Neerlando-Scandinavica. 27 (1–2): 9–16. PMID   2683599.
  9. 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.
  10. Van Ostrand D. "Red Cross Donor Requirements". American Red Cross of Tompkins County. Archived from the original on 3 November 2005. Retrieved 1 August 2005.
  11. Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB (December 2000). "Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests". Clinical Chemistry. 46 (12): 2027–49. doi: 10.1093/clinchem/46.12.2027 . PMID   11106349.
  12. Vespasiani-Gentilucci, Umberto; De Vincentis, Antonio; Ferrucci, Luigi; Bandinelli, Stefania; Incalzi, Raffaele Antonelli; Picardi, Antonio (17 June 2017). "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. PMC   6001897 . PMID   28633440 . Retrieved 24 March 2024.
  13. Shafrir, Asher; Katz, Lior H.; Shauly-Aharonov, Michal; Zinger, Adar; Safadi, Rifaat; Stokar, Joshua; Kalisky, Itay (24 March 2024). "Low ALT Is Associated with IBD and Disease Activity: Results from a Nationwide Study". Journal of Clinical Medicine. 13 (7): 1869. doi: 10.3390/jcm13071869 . ISSN   2077-0383. PMC   11012492 .