Tuesday, November 29, 2011

An interesting hypothesis on the selection of glucose as major fuel source in neurons

Earlier this year, I wondered why neurons preferentially use glucose as fuel. I have now found an interesting paper by Dave Speijer regarding this problem. He proposes the following reasoning to explain this observation:
  • reactive oxygen species are generated in large amounts by NADH dehydrogenase (complex I) when the amount of oxidized ubiquinone is limited
  • generation of large amounts of FADH2 increases the rate of reduction of ubiquinone, and therefore increases indirectly the amount of harmful radical species generated by NADH dehydrogenase
  • glucose oxidation generates a much smaller amount of FADH2 than fatty-acid oxidation. Therefore:


  • Especially vulnerable cells may be expected to have evolved a preference for glucose.

    Incidentally, neurons do seem to lack large amounts of one of the enzymes involved in fatty acid oxidation: thiolase.

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