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Pathway Description
Carnitine Palmitoyl Transferase Deficiency II
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-09-15
Carnitine palmitoyltransferase II deficiency, which is also known as CPT II deficiency, is an inherited inborn error of metabolism (IEM) of fatty acid oxidation leading to muscle weakness. It is the most common inherited disorder of lipid metabolism affecting the skeletal muscle of adults. It is an autosomal recessive disorder associated with a mutation in the enzyme carnitine palmitoyltransferase II. Carnitine palmitoyltransferase II (CPT2) is a peripheral inner mitochondrial membrane protein found in all tissues that oxidize fatty acids. It catalyzes the transesterification of palmitoylcarnitine back into palmitoyl-CoA which is a substrate for beta-oxidation inside the mitochondrial matrix. CPT2 is responsible for the formation of acylcarnitines by catalyzing the transfer of the acyl group of a long-chain fatty acyl-CoA from CoA to carnitine. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. Deficiencies or mutations in the CPT2 gene lead to disorders of long-chain fatty acid oxidation. There are three forms of CPT II deficiency: (1) lethal neonatal form, (2) severe infantile hepatocardiomuscular form, and (3) the myopathic form. More than 300 CPT II deficiency cases have been described with the myopathic form being the most common (myopathic form: 86%, severe infantile form: 8%, neonatal form: 6% of cases). The myopathic form is usually mild and can manifest from infancy to adulthood. The infantile and neonatal forms are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia, cardiomyopathy, seizures, and early death. The adult-onset myopathic form is characterized by exercise-induced muscle pain and weakness, sometimes associated with myoglobinuria. The most common cause of hereditary myoglobinuria is the myopathic form of CPT II deficiency and affects men more than women.
References
Carnitine Palmitoyl Transferase Deficiency II References
Wieser T: Carnitine Palmitoyltransferase II Deficiency
Pubmed: 20301431
Ellis JM, Hasek LY, Yurovich EJ, Harris KL, Goergen CJ: Mouse Carnitine Palmitoyltransferase 2 (CPT2) is required to sustain cardiac function. The Faseb Journal. 2016 Apr 01;30:684.8-684.8. doi: 10.1096/fasebj.30.1_supplement.684.8.
Fatty Acid Metabolism References
Woeltje KF, Esser V, Weis BC, Sen A, Cox WF, McPhaul MJ, Slaughter CA, Foster DW, McGarry JD: Cloning, sequencing, and expression of a cDNA encoding rat liver mitochondrial carnitine palmitoyltransferase II. J Biol Chem. 1990 Jun 25;265(18):10720-5.
Pubmed: 2355018
de Vries Y, Arvidson DN, Waterham HR, Cregg JM, Woldegiorgis G: Functional characterization of mitochondrial carnitine palmitoyltransferases I and II expressed in the yeast Pichia pastoris. Biochemistry. 1997 Apr 29;36(17):5285-92. doi: 10.1021/bi962875p.
Pubmed: 9136891
Brown NF, Esser V, Gonzalez AD, Evans CT, Slaughter CA, Foster DW, McGarry JD: Mitochondrial import and processing of rat liver carnitine palmitoyltransferase II defines the amino terminus of the mature protein. Possibility of differential modification of the rat and human isoforms. J Biol Chem. 1991 Aug 15;266(23):15446-9.
Pubmed: 1869564
Minami-Ishii N, Taketani S, Osumi T, Hashimoto T: Molecular cloning and sequence analysis of the cDNA for rat mitochondrial enoyl-CoA hydratase. Structural and evolutionary relationships linked to the bifunctional enzyme of the peroxisomal beta-oxidation system. Eur J Biochem. 1989 Oct 20;185(1):73-8. doi: 10.1111/j.1432-1033.1989.tb15083.x.
Pubmed: 2806264
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Pubmed: 15489334
Muller-Newen G, Janssen U, Stoffel W: Enoyl-CoA hydratase and isomerase form a superfamily with a common active-site glutamate residue. Eur J Biochem. 1995 Feb 15;228(1):68-73. doi: 10.1111/j.1432-1033.1995.tb20230.x.
Pubmed: 7883013
Kamijo T, Aoyama T, Miyazaki J, Hashimoto T: Molecular cloning of the cDNAs for the subunits of rat mitochondrial fatty acid beta-oxidation multienzyme complex. Structural and functional relationships to other mitochondrial and peroxisomal beta-oxidation enzymes. J Biol Chem. 1993 Dec 15;268(35):26452-60.
Pubmed: 8253773
Uchida Y, Izai K, Orii T, Hashimoto T: Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. II. Purification and properties of enoyl-coenzyme A (CoA) hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein. J Biol Chem. 1992 Jan 15;267(2):1034-41.
Pubmed: 1730633
Arakawa H, Takiguchi M, Amaya Y, Nagata S, Hayashi H, Mori M: cDNA-derived amino acid sequence of rat mitochondrial 3-oxoacyl-CoA thiolase with no transient presequence: structural relationship with peroxisomal isozyme. EMBO J. 1987 May;6(5):1361-6.
Pubmed: 3038520
Yamashita H, Itsuki A, Kimoto M, Hiemori M, Tsuji H: Acetate generation in rat liver mitochondria; acetyl-CoA hydrolase activity is demonstrated by 3-ketoacyl-CoA thiolase. Biochim Biophys Acta. 2006 Jan;1761(1):17-23. doi: 10.1016/j.bbalip.2006.01.001. Epub 2006 Jan 30.
Pubmed: 16476568
Esser V, Britton CH, Weis BC, Foster DW, McGarry JD: Cloning, sequencing, and expression of a cDNA encoding rat liver carnitine palmitoyltransferase I. Direct evidence that a single polypeptide is involved in inhibitor interaction and catalytic function. J Biol Chem. 1993 Mar 15;268(8):5817-22.
Pubmed: 8449948
Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, Hashimoto T, Yamamoto T: Structure and regulation of rat long-chain acyl-CoA synthetase. J Biol Chem. 1990 May 25;265(15):8681-5.
Pubmed: 2341402
Distler AM, Kerner J, Hoppel CL: Post-translational modifications of rat liver mitochondrial outer membrane proteins identified by mass spectrometry. Biochim Biophys Acta. 2007 May;1774(5):628-36. doi: 10.1016/j.bbapap.2007.03.012. Epub 2007 Mar 28.
Pubmed: 17478130
Iijima H, Fujino T, Minekura H, Suzuki H, Kang MJ, Yamamoto T: Biochemical studies of two rat acyl-CoA synthetases, ACS1 and ACS2. Eur J Biochem. 1996 Dec 1;242(2):186-90. doi: 10.1111/j.1432-1033.1996.0186r.x.
Pubmed: 8973631
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000541
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