Abstract
The fatty acid composition was determined of liver, skeletal muscle and heart obtained post mortem from patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD), multiple acyl-CoA dehydrogenase deficiency (MADD) and very long-chain acyl-CoA dehydrogenase deficiency (VLCADD). Increased amounts of 4-decenoic acid 10:1(n−6), 5-dodecenoic acid 12:1(n−7), 5-tetradecenoic acid 14:1(n−9), 5,8-tetradecadienoic acid 14:2(n−6) and 7,10-hexadecadienoic acid 16:2(n−6)—intermediates of unsaturated fatty acid oxidation—were found. Fractionation into different lipid classes showed that these fatty acids were exclusively present in the triglyceride fraction. They could not be detected in the free fatty acid fraction or in the phospholipid fraction. Our results suggest that intermediates of unsaturated fatty acid oxidation that accumulate as a consequence of MCADD, MADD and VLCADD are transported to the endoplasmic reticulum for esterification into neutral glycerolipids. The pattern of accumulation is characteristic for each disease, which makes fatty acid analysis of total lipid of post-mortem tissues a useful tool in the detection of mitochondrial fatty acid oxidation defects in patients who died unexpected, for example with sudden infant death syndrome.
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REFERENCES
Andresen BS, Olpin S, Poorthuis BJHM, et al (1999) Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. Am J Hum Genet 64: 479-494.
Boles RG, Martin SK, Blitzer MG, Rinaldo P (1994) Biochemical diagnosis of fatty acid oxidation disorders by metabolite analysis of postmortem liver. Hum Pathol 25: 735-741.
Boles RG, Buck EA, Blitzer MG, et al (1998) Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life. J Pediatr 132: 924-933.
DeMar Jr JC, Wensel TG, Anderson RE (1996) Biosynthesis of the unsaturated 14-carbon fatty acids found on the N termini of photoreceptor-specific proteins. J Biol Chem 271: 5007-5016.
Divry P, Vianey-Saban C, Mathieu M (1999) Determination of total fatty acids in plasma: cis-5-tetradecenoic acid (C14:1ω-9) in the diagnosis of long-chain fatty acid oxidation defects. J Inherit Metab. Dis 22: 286-288.
Dommes V, Kunau W-H (1984) Purification and properties of acyl coenzyme A dehydrogenases from bovine liver. J Biol Chem 259: 1789-1797.
Duran M, Bruinvis L, Ketting D, De Klerk JBC, Wadman SK (1988) cis-4-Decenoic acid in plasma: a characteristic metabolite in medium-chain acyl-CoA dehydrogenase deficiency. Clin Chem 34: 548-551.
Folch J, Lees M, Sloane Stanley GH (1975) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497-509.
Galloway JH, Cartwright IJ, Bennett MJ (1987) Abnormal myocardial lipid composition in an infant with type II glutaric aciduria. J Lipid Res 28: 279-284.
Heales SJR, Woolf DA, Robinson P, Leonard JV (1991) Rapid diagnosis of medium-chain acyl-CoA dehydrogenase deficiency by measurement of cis-4-decenoic acid in plasma. J Inherit Metab Dis 14: 661-667.
Kates M (1986). Techniques of Lipidology, 2nd revised edn. Amsterdam: Elsevier Science.
Kelly RI (1992) Beta-oxidation of long-chain fatty acids by human fibroblasts: evidence for a novel long-chain acyl coenzyme A dehydrogenase. Biochem Biophys Res Commun 182: 1002-1007.
Lepage G, Roy CC (1986) Direct transesterification of all classes of lipids in a one-step reaction. J Lipid Res 7: 114-120.
Onkenhout W, Venizelos V, Van der Poel PFH, Van den Heuvel MPM, Poorthuis BJHM (1995) Identification and quantification of intermediates of unsaturated fatty acid metabolism in plasma of patients with fatty acid oxidation disorders. Clin Chem 41: 1467-1474.
Roe CR, Coates PM (1995) Mitochondrial fatty acid oxidation disorders. In Scriver CR, Beaudet AL, Sly WL, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease 7th edn. New York: McGraw-Hill, 1501-1533.
Scholte HR, De Klerk JBC, Boonman AMC, et al (1992) Glutaric aciduria type II with secondary deficiency of complex III, IV and CPT I in liver and of complex I, III and IV in heart. 31st Meeting of the Society for the Study of Inborn Errors of Metabolism, Manchester, P 074 [Abstract].
Smelt AHM, Poorthuis BJHM, Onkenhout W, et al (1998) Very long-chain acyl coenzyme A dehydrogenase deficiency with adult onset. Ann Neurol 43: 540-544.
Spector AA, Williard DE, Kaduce TL, Gordon JA (1997) Conversion of arachidonic acid to tetradecadienoic acid by peroxisomal oxidation. Prostaglandins, Leukotrienes and Essential Fatty Acids 57: 101-105.
Vance DE, Sweeley CC (1967) Quantitative determination of the neutral glycosyl ceramides in human blood. J Lipid Res 8: 621-630.
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Onkenhout, W., Venizelos, V., Scholte, H.R. et al. Intermediates of unsaturated fatty acid oxidation are incorporated in triglycerides but not in phospholipids in tissues from patients with mitochondrial β-oxidation defects. J Inherit Metab Dis 24, 337–344 (2001). https://doi.org/10.1023/A:1010592232317
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DOI: https://doi.org/10.1023/A:1010592232317