Diagnóstico de la deficiencia de Acil-CoA deshidrogenasa de cadena media mediante el uso de sustratos tritiados.

Abstract

The medium-chain acyl-CoA dehydrogenase (MCAD) is the key enzyme for degrading fatty acids with a chain of 10 to 12 atoms of carbon. Its deficiency should be confirmed using laboratory methods. During the present work, fibroblasts from patients who presented MCAD deficiency were incubated, in tritiated substrates. A significant difference (P<0.05) was found when comparing palmitate and miristate between controls and patients with MCAD deficiency. The triatiated miristate presented a more depressed oxidation in comparison to palmitate.

Keywords:

MCAD

ácidos grasos

metabolismo

MCAD

fatty acids

metabolism

References

Derks TG, Boer TS, van Assen A, Bos T, Ruiter J, Waterham HR, et al. Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in The Netherlands: the importance of enzyme analysis to ascertain true MCAD deficiency. J Inherit Metab Dis. 2008;31(1):88-96.

Zeng J, Liu Y, Wu L, Li D. Mutation of Tyr375 to Lys375 allows medium-chain acyl-CoA dehydrogenase to acquire acyl-CoA oxidase activity. Biochim Biophys Acta. 2007;1774:1628-1634.

Santos L, Patterson A, Moreea SM, Lippiatt CM, Walter J, Henderson M. Acute liver failure in pregnancy associated with maternal MCAD deficiency. J. Inherit Metab Dis. 2007;30:103.

Cyriac J, Venkatesh V, Gupta C.A fatal neonatal presentation of medium-chain acyl coenzyme a dehydrogenase deficiency. J Int Med Res. 2008;36:609-610.

Yang Z, Lantz PE, Ibdah JA. Post-mortem analysis for two prevalent beta-oxidation mutations in sudden infant death. Pediatr Int. 2007;49:883-7.

Osorio JH. Patología molecular de los errores hereditarios de la ß-oxidación mitocondrial de los ácidos grasos: alcances en el diagnóstico y tratamiento. Biosalud. 2006;5:71-83.

Lowry OH, Rosebrough NJ, Farr Al, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265-275.

Manning NJ, Olpin SE, Pollit RJ, Webley JA. Comparison of 9.10-3HPalmitic and 9.10-3Hmyristic acids for the detection of defects of fatty acid oxidation in intact cultured fibroblasts. J Inher Metab Dis. 1990;13:58-68.

Olpin SE, Manning NJ, Carpenter K, Middleton B, Pollit RJ. Differential diagnosis of hydroxydicarboxylic aciduria based on release of 3H2O from [9,10-3H]-myristic and [9,10-3H]-palmitic acids by intact cultured fibroblasts. J Inher Metab Dis. 1992;15:883-890.

Kolvraa S, Gregersen N, Christiensen E, Hobolth N. In vitro fibroblasts studies in a patient with C6-C10 dicarboxilic aciduria: evidence for a defect in general acyl-CoA dehydrogenase. Clin Chim Acta. 1982;126:53-67.

Saudubray JM, Coude FX, Demaugre F, Johnson C, Gibson KM, Nyhan WL. Oxidation of fatty acids in cultured fibroblasts: a model system for the detection and study of defects in oxidation. Pediatr Res. 1982;16:877-881.

Rhead WJ, Moon A, Oettger V, Henkle K. 14CO2-Labelled sustrate catabolism by human diploid fibroblasts derived from infants and adults. Biochem Med. 1985;34:182-188.

Veerkamp JH, Van Moerkerk HTB, Glatz JFC, Zuurveld JGEM, Jacobs AEM, et al. 14CO2 production is no measure of [14C]fatty acid oxidation. Biochem. Med Metab Biol. 1986;16:248-259.

Moon A, Rhead WJ. Complementation analysis of fatty acid oxidation disorders. J Clin Invest. 1987;79:56-94.

Nada MA, Rhead JW, Sprecher H, Schulz H, Roe CR. Evidence for intermediate channeling in mitochondrial ß-oxidation. J Biol Chem. 1985;270:530-535.

Olpin SE, Manning NJ, Pollit, RJ, Clarke S. Improved detection of long chain fatty acid oxidation defects in intact cells using [9,10-3H]-oleic acid. J Inher Metab Dis. 1997;20:415-419.