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Pathway Description
3-Hydroxy-3-methylglutaryl-CoA Lyase Deficiency
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-08-30
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (3-Hydroxy-3-methylglutaric acidemia; Leucine metabolism, defect in, HMG-CoA lyase deficiency) is an autosomal recessive disease caused by a mutation in the HMGCL gene which codes for hydroxymethylglutaryl-CoA lyase. A deficiency in this enzyme results in accumulation of 3-hydroxymethylglutaric acid, 3-hydroxyisovaleric acid, 3-methylcrotonylglycine and 3-methylglutaconic acid (cis and trans form), and methylglutaric acid in urine; and ammonia in blood. Symptoms include cardiomyopathy, dehydration, hypotonia, lactic acidosis, and pancreatitis. Treatment includes a low-fat, low-protein, high-carbohydrate diet.
References
3-Hydroxy-3-methylglutaryl-CoA Lyase Deficiency References
Barash V, Mandel H, Sella S, Geiger R: 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: biochemical studies and family investigation of four generations. J Inherit Metab Dis. 1990;13(2):156-64.
Pubmed: 2116546
Wang SP, Marth JD, Oligny LL, Vachon M, Robert MF, Ashmarina L, Mitchell GA: 3-Hydroxy-3-methylglutaryl-CoA lyase (HL): gene targeting causes prenatal lethality in HL-deficient mice. Hum Mol Genet. 1998 Dec;7(13):2057-62.
Pubmed: 9817922
Valine, Leucine, and Isoleucine Degradation References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
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Pubmed: 16141072
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Pubmed: 15489334
Ballif BA, Carey GR, Sunyaev SR, Gygi SP: Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain. J Proteome Res. 2008 Jan;7(1):311-8. doi: 10.1021/pr0701254. Epub 2007 Nov 23.
Pubmed: 18034455
Fitzgerald J, Hutchison WM, Dahl HH: Isolation and characterisation of the mouse pyruvate dehydrogenase E1 alpha genes. Biochim Biophys Acta. 1992 May 7;1131(1):83-90. doi: 10.1016/0167-4781(92)90102-6.
Pubmed: 1581363
Tamura T, McMicken HW, Smith CV, Hansen TN: Gene structure for mouse glutathione reductase, including a putative mitochondrial targeting signal. Biochem Biophys Res Commun. 1997 Aug 18;237(2):419-22. doi: 10.1006/bbrc.1997.7153.
Pubmed: 9268726
Tutic M, Lu XA, Schirmer RH, Werner D: Cloning and sequencing of mammalian glutathione reductase cDNA. Eur J Biochem. 1990 Mar 30;188(3):523-8. doi: 10.1111/j.1432-1033.1990.tb15431.x.
Pubmed: 2185014
Wang S, Nadeau JH, Duncan A, Robert MF, Fontaine G, Schappert K, Johnson KR, Zietkiewicz E, Hruz P, Miziorko H, et al.: 3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL): cloning and characterization of a mouse liver HL cDNA and subchromosomal mapping of the human and mouse HL genes. Mamm Genome. 1993;4(7):382-7.
Pubmed: 8102917
Wang SP, Robert MF, Gibson KM, Wanders RJ, Mitchell GA: 3-Hydroxy-3-methylglutaryl CoA lyase (HL): mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients. Genomics. 1996 Apr 1;33(1):99-104. doi: 10.1006/geno.1996.0164.
Pubmed: 8617516
Schuldiner O, Eden A, Ben-Yosef T, Yanuka O, Simchen G, Benvenisty N: ECA39, a conserved gene regulated by c-Myc in mice, is involved in G1/S cell cycle regulation in yeast. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7143-8. doi: 10.1073/pnas.93.14.7143.
Pubmed: 8692959
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Pubmed: 2251142
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 SMP0000138
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