Very long-chain acyl CoA dehydrogenase

Enzymes 7,9, and 13 form a trifunctional protein associated with the inner face of the inner mitochondrial membrane. Very-long-chain acyl-CoA dehydrogenase is also associated with other inner mitochondrial membranes while the other enzymes are in the matrix and may be loosely associated with the inner face of the inner membrane. A medium-chain 2-enoyl-CoA hydratase may also be present in the mitochondrial matrix. 

Very-long-chain acyl-CoA dehydrogenase and trifunctional protein are the two inner membrane-bound... 

Roe DS, Vianey-Saban C, SharmaS, ZabotMT, Roe CR (2001) Oxidation of unsaturated fatty acids by human fibroblasts with very-long-chain acyl-CoA dehydrogenase deficiency aspects of substrate specificity and correlation with clinical phenotype. Clin Chim Acta 312 55-67... 

Very Long-Chain Acyl-CoA Dehydrogenase Deficiency... 

Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive condition. In the mid 1980s, patients with VLCAD deficiency were initially described as having long-chain acyl-CoA dehydrogenase (LCAD) deficiency. However, without exception, once the VLCAD protein was identified, affected patients were shown to have no detectable VLCAD protein by immunobiot analy-sis or to harbor disease-causing mutations in the VLCAD... 

Figure 55-14 Plasma profiles of plasma acylcarnitine butyl-ester derivatives. A, Normal control. B, Propionic acidemia. C, Short-chain acyl-CoA dehydrogenase deficiency. D, Isovaleric acidemia. E, Medium-chain acyl-CoA dehydrogenase deficiency. F, Very long-chain acyl-CoA dehydrogenase deficiency. G, Long-chain L-3-hydroxy acyl-CoA dehydrogenase deficiency.The symbol marks internal standards [ Hjj-acetylcarnitine (m/z 263) [ HaJ-propionylcarnitine (m/z 277) fH ]-butyrylcarnitlne (m/z 295) pHal-octanoylcarnitine (m/z 347) [ Haj-dodecanoylcarnltine (m/z 403) [ Haj-palmitoy I carnitine (m/z 459).

VLCAD deficiency 201475 Very long-chain acyl-CoA dehydrogenase >1 75,000 Spectrurn from early onset cardiomyopathy, coma, liver disease to adult onset myopathy ... 

Andresen BS, Olpin S, Poorthuis BJ, Scholte HR, Vianey-Saban C, Wanders R, et al. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. Am J Hum Genet 1999 64 479-94. 

Aoyama T, Ueno I, Kamijo T, Hashimoto T. Rat very-long-chain acyl-CoA dehydrogenase, a novel mitochondrial acyl-CoA dehydrogenase gene product, is a rate-limiting enzyme in long-chain fatty acid beta-oxidation system. cDNA and deduced amino acid sequence and distinct specificities of the cDNA-expressed protein. J Biol Chem 1994 269 19088-94. 

Spiekerkoetter U, Sun B, Zytkovicz T, Wanders R, Strauss AW, Wendel U. MS/MS-hased newhom and family screening deteds asymptomatic patients with very-long-chain acyl-CoA dehydrogenase defidency. J Pediatr. 2003 Sep 143(3) 335-42. PubMed dtation... 

Touma EH, Rashed MS, Vianey-Saban C, Sakr A, Divry P, Gregersen N, Andresen BS. A severe genotype with favourable outcome in very long chain acyl-CoA dehydrogenase defidency. Arch Dis Child. 2001 Jan 84(l) 58-60. PubMed dtation... 

Souri M, Aoyama T, Hoganson G, Hashimoto T. Very-long-chain acyl-CoA dehydrogenase subunit assembles to the dimer form on mitochondrial inner membrane. FEBS Lett. 1998 Apr 17 426(2) 187-90. PubMed dtation... 

This first step is catalyzed by three isozymes of acyl-CoA dehydrogenase, each specific for a range of fatty-acyl chain lengths very-long-chain acyl-CoA dehydrogenase (VLCAD), acting on fatty acids of 12 to 18... 

Izai, K., Y. Uchida, T. Orii, S. Yamamoto T. Hashimoto (1992)J. Biol. Chem. 267, 1027-1033. Novel fatty acid P-oxidation enzymes in rat liver mitochondria. I Purification and properties of very-long-chain acyl-CoA dehydrogenase. 

The long chain defects, very long-chain acyl-CoA dehydrogenase deficiency (VLCAD) and long-chain 3-hydroxacyl-CoA dehydrogenase deficiency (LCHAD), generally give a low P/M ratio. The mean P/M ratio for LCHAD is 0.60 0.07 (n = 18) and... 

ASSAYS WITH [9,10- OLEATE VERY LONG-CHAIN ACYL CoA DEHYDROGENASE DEFICIENCY... 

Biochemical studies in fibroblasts from the index patient showed that the rate of P-oxidation of myristate and palmitate was severely decreased to less than 5% of the controls (Table 1). Enzyme measurements of the very-long chain acyl-CoA dehydrogenase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, thiolase, carnitine palmitoyltransferase I and II showed normal activities (not shown). The severe deficiency of long chain fatty acid oxidation was explained by the complete deficiency of CAC activity (Table 1). 

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