Does Negative Hyperconjugation Assist Enzymatic Dehydrogenations?

Gloria Tabacchi, Maria A. Vanoni, Aldo Gamba, Ettore Fois
  • ChemPhysChem, June 2007, Wiley
  • DOI: 10.1002/cphc.200700085

The role of the substrate in enzymatic dehydrogenations

What is it about?

Using calculations we show that an intrinsic molecular property (called "negative hyperconjugation") governs the oxidation chemistry of L-lactate and may help to determine its enzymatic dehydrogenation mechanism.

Why is it important?

Flavoenzymes are a class of enzymes implicated in fundamental reactions of cell metabolism. How do these enzymes work? The question is still open for the oxidation of L-lactate in flavocytochrome-b2. We found that the oxidation mechanism of L-lactate in this enzyme is governed by a specific property of the substrate. We found this property to be also present in the substrates of other flavoenzymes, for which the mechanism was known. This validates and generalizes our findings. Hence, calculations on substrate molecules can give us precious information on the inner workings of an important class of enzymes.


Gloria Tabacchi
university of insubria

When I started this project, the mechanism of L-lactate dehydrogenation in this enzyme was a matter of intense debate. However, besides the actual mechanistic details of the reaction, the most original aspect of our work was to focus attention on the intrinsic properties of the substrate. One of such properties could help to predict the dehydrogenation mechanism of the substrate in the enzyme active site. I think that this finding sets general basis for understanding how flavoenzymes work.

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The following have contributed to this page: Gloria Tabacchi