Fuel for brain

[simplycurious]

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Why does the brain heavily rely on glucose for its functions and not fatty acids?

 

[Chipster.]

God had a sweet tooth.

 

[Kelevra]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790936/ (Published 2013)

From the article:

"Neural cells have very high, but fluctuating ATP requirements. Despite the fact that fatty acids are the substrates richest in hydrogen for supplying redox energy to the mitochondrial ETC, they are not used significantly as fuel in neural cells. High susceptibility of brain tissue to oxidative stress is generally claimed to be the underlying reason. However, evolution has eliminated the enzymatic activity of fatty acid oxidation in brain mitochondria. We hypothesize that this helps to protect neural cells against enhanced oxidative stress. Considering the low anti-oxidative defense capacity in neural cells and the fact that β-oxidation is a most prominent source of ROS generation, this provides a convincing explanation for the finding of low enzymatic capacity for fatty acid degradation in neural cells. In addition, we speculate that the situation of the energy metabolism in neural cells of the gray matter could be compared with that of fast-twitching muscle fibers.

To support fast-twitching skeletal muscle tissue rapidly with ATP, the ATP regeneration has to be based on glucose degradation. ATP regeneration based on the oxidative fatty acid degradation is too slow. Quantitatively, it has been estimated that the rate of ATP generation based on the carbohydrate oxidation is in the range of 0.51 to 0.68

mmol per second per kg body mass.81 In comparison, the rate of ATP generation based on triacylglycerol fueling is approximately two- to threefold lower (0.24

mmol per second per kg body mass). We argue that, as a consequence, the overall process starting from the liberation of NEFA in the white adipose tissue to their oxidation in the matrix compartment of neural mitochondria is much too slow for supplying enough ATP to neurons with rapid sustained firing."


I didn't read the full article, or check the study parameters, but their conclusion is certainly not unreasonable, and poses fair evolutionary speculation, based on their findings of neuronal metabolism.

 

[simplycurious]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790936/ (Published 2013)

From the article:

"Neural cells have very high, but fluctuating ATP requirements. Despite the fact that fatty acids are the substrates richest in hydrogen for supplying redox energy to the mitochondrial ETC, they are not used significantly as fuel in neural cells. High susceptibility of brain tissue to oxidative stress is generally claimed to be the underlying reason. However, evolution has eliminated the enzymatic activity of fatty acid oxidation in brain mitochondria. We hypothesize that this helps to protect neural cells against enhanced oxidative stress. Considering the low anti-oxidative defense capacity in neural cells and the fact that β-oxidation is a most prominent source of ROS generation, this provides a convincing explanation for the finding of low enzymatic capacity for fatty acid degradation in neural cells. In addition, we speculate that the situation of the energy metabolism in neural cells of the gray matter could be compared with that of fast-twitching muscle fibers.

To support fast-twitching skeletal muscle tissue rapidly with ATP, the ATP regeneration has to be based on glucose degradation. ATP regeneration based on the oxidative fatty acid degradation is too slow. Quantitatively, it has been estimated that the rate of ATP generation based on the carbohydrate oxidation is in the range of 0.51 to 0.68

mmol per second per kg body mass.81 In comparison, the rate of ATP generation based on triacylglycerol fueling is approximately two- to threefold lower (0.24

mmol per second per kg body mass). We argue that, as a consequence, the overall process starting from the liberation of NEFA in the white adipose tissue to their oxidation in the matrix compartment of neural mitochondria is much too slow for supplying enough ATP to neurons with rapid sustained firing."


I didn't read the full article, or check the study parameters, but their conclusion is certainly not unreasonable, and poses fair evolutionary speculation, based on their findings of neuronal metabolism.

Well I suppose the gist of it is: to prevent oxidative damage to neural tissues and to ensure a steady and rapid supply of ATPs (when required at short notice) the brain goes for glucose oxidation. Thank you for the explanation.

 

[Kelevra]

Well I suppose the gist of it is: to prevent oxidative damage to neural tissues and to ensure a steady and rapid supply of ATPs (when required at short notice) the brain goes for glucose oxidation. Thank you for the explanation.

Hooray for open source learning, eh?