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The question is rather straight forward: I have always been curious as to why, but cannot find an explanation online.

I can imagine that the mechanism is different for each, but why does brain tissue and red blood cells use specifically and only glucose for energy metabolism?

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    $\begingroup$ None of the answers below go to the core of the problem. Sure, several systems have been shut off or turned down in neurons and erythrocytes limiting their fuel types. The more important and possibly unanswered question is why these cells evolved this way. See also this related question on the brain. $\endgroup$
    – SeanJ
    Commented May 31, 2017 at 9:06

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In the case of red blood cells: human erythrocytes (red blood cells) have no mitochondria. Since the mitochondria are the cellular site for oxidative metabolism of fatty acids, erythrocytes cannot oxidise fatty acids to release energy. The erythrocytes also cannot fully oxidise glucose (to carbon dioxide and water) because this is also a mitochondrial process, so they have to rely upon anaerobic glycolysis. The end product of anaerobic glycolysis is pyruvate, and erythrocytes reduce this to lactate (to recycle the NADH that is produced during glycolysis) and then export this lactate into the blood for further metabolism by the liver.

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The brain and heart can take advantage of ketone bodies when the amount of glucose is low. These are byproducts of fat metabolism and can be converted to acetyl-coA via the citric acid cycle.

Overproduction of these products can cause pathological conditions:

When the rate of synthesis of ketone bodies exceeds the rate of utilization ,their concentration in blood increases , this is known as ketonemia. This is followed by ketonuria- excretion of ketone bodies in urine. The overall picture of ketonemia and ketouria is commonly referred as ketosis. Smell of acetone in breath is a common feature in ketosis.

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    $\begingroup$ There is quite a bit of evidence that the brain normally uses lactate produced by astrocytes as a source of energy. nature.com/jcbfm/journal/v25/n10/full/9600127a.html $\endgroup$
    – nico
    Commented Jul 20, 2012 at 11:08
  • $\begingroup$ @nico Sounds like that could almost be its own answer. I wasn't aware of that. $\endgroup$
    – jonsca
    Commented Jul 20, 2012 at 11:25
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    $\begingroup$ unfortunately I know about the topic only superficially and right now I do not have time to go through the literature $\endgroup$
    – nico
    Commented Jul 20, 2012 at 13:06
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Lipid catabolism provides energy mainly through fatty acid beta-oxidation. This process goes through a spiral of four mitochondrial enzymatic steps: one is catalyzed by the mitochondrial trifunctional3-ketoacyl-CoA thiolase (gene HADH). The activity of this thiolase is very low in neurons, explaining the brain need of alternative energy sources. Yang et al., JBC 1987. As previosly mentioned, developing erythrocytes eliminates mitochondria trough autophagy (mitophagy), therefore they became unable to efficiently perform lipid catabolism.

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  • $\begingroup$ But why the activity of the thiolase you mention is low in neurons? Has it any functional purpose? $\endgroup$
    – Marta Cz-C
    Commented Aug 31, 2012 at 17:27

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