Acyl-CoA dehydrogenases - a mechanistic overview

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2004
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Thorpe, Colin
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European Journal of Biochemistry ; 271 (2004), 3. - pp. 494-508. - ISSN 0014-2956. - eISSN 1432-1033
Abstract
Acyl-CoA dehydrogenases constitute a family of flavoproteins that catalyze the α,β-dehydrogenation of fatty acid acyl-CoA conjugates. While they differ widely in their specificity, they share the same basic chemical mechanism of α,β-dehydrogenation. Medium chain acyl-CoA dehydrogenase is probably the best-studied member of the class and serves as a model for the study of catalytic mechanisms. Based on medium chain acyl-CoA dehydrogenase we discuss the main factors that bring about catalysis, promote specificity and determine the selective transfer of electrons to electron transferring flavoprotein. The mechanism of α,β-dehydrogenation is viewed as a process in which the substrate αC-H and βC-H bonds are ruptured concertedly, the first hydrogen being removed by the active center base Glu376-COO as an H+, the second being transferred as a hydride to the flavin N(5) position. Hereby the pKa of the substrate αC-H is lowered from > 20 to ≈ 8 by the effect of specific hydrogen bonds. Concomitantly, the pKa of Glu376-COO is also raised to 8 9 due to the decrease in polarity brought about by substrate binding. The kinetic sequence of medium chain acyl-CoA dehydrogenase is rather complex and involves several intermediates. A prominent one is the molecular complex of reduced enzyme with the enoyl-CoA product that is characterized by an intense charge transfer absorption and serves as the point of transfer of electrons to the electron transferring flavoprotein. These views are also discussed in the context of the accompanying paper on the three-dimensional properties of acyl-CoA dehydrogenases.
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570 Biosciences, Biology
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fatty acid beta-oxidation,acyl-CoA dehydrogenase,acyl-CoA oxidase alpha,beta-dehydrogenation,mechanisms
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ISO 690GHISLA, Sandro, Colin THORPE, 2004. Acyl-CoA dehydrogenases - a mechanistic overview. In: European Journal of Biochemistry. 271(3), pp. 494-508. ISSN 0014-2956. eISSN 1432-1033. Available under: doi: 10.1046/j.1432-1033.2003.03946.x
BibTex
@article{Ghisla2004AcylC-8793,
  year={2004},
  doi={10.1046/j.1432-1033.2003.03946.x},
  title={Acyl-CoA dehydrogenases - a mechanistic overview},
  number={3},
  volume={271},
  issn={0014-2956},
  journal={European Journal of Biochemistry},
  pages={494--508},
  author={Ghisla, Sandro and Thorpe, Colin}
}
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