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    Topic review

    CPT1A Gene

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    Submitted by: Vicky Zhou
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    carnitine palmitoyltransferase 1A

    1. Normal Function

    The CPT1A gene provides instructions for making an enzyme called carnitine palmitoyltransferase 1A, which is found in the liver. This enzyme is essential for fatty acid oxidation, a multistep process that breaks down (metabolizes) fats and converts them into energy. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids cannot enter mitochondria unless they are attached to a substance known as carnitine. Carnitine palmitoyltransferase 1A connects carnitine to long-chain fatty acids so they can cross the inner membrane of mitochondria. Once these fatty acids are inside mitochondria, carnitine is removed and they can be metabolized to produce energy. During periods of fasting, long-chain fatty acids are an important energy source for the liver and other tissues.

    2. Health Conditions Related to Genetic Changes

    2.1. Carnitine Palmitoyltransferase I Deficiency

    More than 20 mutations in the CPT1A gene have been found to cause carnitine palmitoyltransferase I (CPT I) deficiency. Most of these mutations change single protein building blocks (amino acids) within carnitine palmitoyltransferase 1A. Mutations in the CPT1A gene severely reduce or eliminate the activity of this enzyme. Without enough of this enzyme, carnitine is not attached to long-chain fatty acids. As a result, these fatty acids cannot enter mitochondria and be converted into energy. Reduced energy production can lead to some of the features of CPT I deficiency, such as low blood sugar (hypoglycemia) and low levels of the products of fat breakdown (hypoketosis). Fatty acids may also build up in cells and damage the liver, heart, and brain. This abnormal buildup causes the other signs and symptoms of the disorder.

    2.2. Other Disorders

    CPT1A gene mutations appear to increase the risk of a serious liver disorder that can develop in women during pregnancy. This disorder, called acute fatty liver of pregnancy, begins with abdominal pain and can rapidly progress to liver failure. Signs of acute fatty liver of pregnancy include an abnormal accumulation of fat in the liver, hypoglycemia, increased levels of ammonia in the blood (hyperammonemia), and abnormalities in liver enzymes. A small percentage of women who have a mutation in one copy of the CPT1A gene in each cell and are carrying a fetus with mutations in both copies of the CPT1A gene develop this maternal liver disease. Little is known about the relationship between CPT1A gene mutations and liver problems in the mother during pregnancy.

    3. Other Names for This Gene

    • carnitine palmitoyltransferase 1A (liver)
    • carnitine palmitoyltransferase I, liver
    • CPT1
    • CPT1-L
    • CPT1A_HUMAN
    • L-CPT1

    This entry is adapted from https://medlineplus.gov/genetics/gene/cpt1a

    References

    1. Akkaoui M, Cohen I, Esnous C, Lenoir V, Sournac M, Girard J, Prip-Buus C.Modulation of the hepatic malonyl-CoA-carnitine palmitoyltransferase 1Apartnership creates a metabolic switch allowing oxidation of de novo fatty acids.Biochem J. 2009 May 27;420(3):429-38. doi: 10.1042/BJ20081932.
    2. Bennett MJ, Boriack RL, Narayan S, Rutledge SL, Raff ML. Novel mutations inCPT 1A define molecular heterogeneity of hepatic carnitine palmitoyltransferase Ideficiency. Mol Genet Metab. 2004 May;82(1):59-63.
    3. Bennett MJ, Santani AB. Carnitine Palmitoyltransferase 1A Deficiency. 2005 Jul27 [updated 2016 Mar 17]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, BeanLJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA):University of Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1527/
    4. Bonnefont JP, Djouadi F, Prip-Buus C, Gobin S, Munnich A, Bastin J. Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects. MolAspects Med. 2004 Oct-Dec;25(5-6):495-520. Review.
    5. Brown NF, Mullur RS, Subramanian I, Esser V, Bennett MJ, Saudubray JM,Feigenbaum AS, Kobari JA, Macleod PM, McGarry JD, Cohen JC. Molecularcharacterization of L-CPT I deficiency in six patients: insights into function ofthe native enzyme. J Lipid Res. 2001 Jul;42(7):1134-42.
    6. Gobin S, Bonnefont JP, Prip-Buus C, Mugnier C, Ferrec M, Demaugre F, SaudubrayJM, Rostane H, Djouadi F, Wilcox W, Cederbaum S, Haas R, Nyhan WL, Green A, Gray G, Girard J, Thuillier L. Organization of the human liver carnitinepalmitoyltransferase 1 gene ( CPT1A) and identification of novel mutations inhypoketotic hypoglycaemia. Hum Genet. 2002 Aug;111(2):179-89.
    7. Gobin S, Thuillier L, Jogl G, Faye A, Tong L, Chi M, Bonnefont JP, Girard J,Prip-Buus C. Functional and structural basis of carnitine palmitoyltransferase 1Adeficiency. J Biol Chem. 2003 Dec 12;278(50):50428-34.
    8. Longo N, Amat di San Filippo C, Pasquali M. Disorders of carnitine transportand the carnitine cycle. Am J Med Genet C Semin Med Genet. 2006 May15;142C(2):77-85. Review.
    9. Prasad C, Johnson JP, Bonnefont JP, Dilling LA, Innes AM, Haworth JC, BeischelL, Thuillier L, Prip-Buus C, Singal R, Thompson JR, Prasad AN, Buist N, GreenbergCR. Hepatic carnitine palmitoyl transferase 1 (CPT1 A) deficiency in NorthAmerican Hutterites (Canadian and American): evidence for a founder effect andresults of a pilot study on a DNA-based newborn screening program. Mol GenetMetab. 2001 May;73(1):55-63.
    10. Ramsay RR, Zammit VA. Carnitine acyltransferases and their influence on CoApools in health and disease. Mol Aspects Med. 2004 Oct-Dec;25(5-6):475-93.Review.
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