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Gene Review:

ACADL - acyl-CoA dehydrogenase, long chain

Sus scrofa

Eder, M. et al., Lee, H.J. et al., Kieweg, V. et al., Bertrand, C. et al.

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Disease relevance of ACADL

Long-chain-acyl-CoA dehydrogenase (LCADH) has been produced by recombinant techniques from the human cDNA and purified after expression in Escherichia coli [1].

High impact information on ACADL

The catalytic base responsible for the alpha-proton abstraction from the thioester substrate is Glu376 in MCADH, while that in LCADH is Glu255 (MCADH numbering), located over 100 residues away in its primary amino acid sequence [2].
Both LCADH are inactivated by the substrate analogue 2-octynoyl-CoA, possibly via covalent modification of Glu261, the active-site residue involved in deprotonation of the substrate (alpha)C-H [1].
The substrate specificity of the mutant is broader with a less pronounced activity peak resembling long-chain acyl-CoA dehydrogenase [3].
We conclude that human LCADH is either quantitatively less important in beta-oxidation than in the pig, or that post-translational modifications, not present in the recombinant human enzyme, are required to optimize human LCADH activity [1].
MCAD deficiency was demonstrated in fibroblasts from nine patients and LCAD deficiency in fibroblasts from two patients [4].

References

Characterization of human and pig kidney long-chain-acyl-CoA dehydrogenases and their role in beta-oxidation. Eder, M., Kräutle, F., Dong, Y., Vock, P., Kieweg, V., Kim, J.J., Strauss, A.W., Ghisla, S. Eur. J. Biochem. (1997) [Pubmed]
Crystal structures of the wild type and the Glu376Gly/Thr255Glu mutant of human medium-chain acyl-CoA dehydrogenase: influence of the location of the catalytic base on substrate specificity. Lee, H.J., Wang, M., Paschke, R., Nandy, A., Ghisla, S., Kim, J.J. Biochemistry (1996) [Pubmed]
Biochemical characterization of purified, human recombinant Lys304-->Glu medium-chain acyl-CoA dehydrogenase containing the common disease-causing mutation and comparison with the normal enzyme. Kieweg, V., Kräutle, F.G., Nandy, A., Engst, S., Vock, P., Abdel-Ghany, A.G., Bross, P., Gregersen, N., Rasched, I., Strauss, A., Ghisla, S. Eur. J. Biochem. (1997) [Pubmed]
Purification of electron transfer flavoprotein from pig liver mitochondria and its application to the diagnosis of deficiencies of acyl-CoA dehydrogenases in human fibroblasts. Bertrand, C., Dumoulin, R., Divry, P., Mathieu, M., Vianey-Saban, C. Clin. Chim. Acta (1992) [Pubmed]

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