Ketone bodies - general question

[bluequestions]

I've searched through the forum and still couldn't quite find a certain answer. I understand in the starvation state, body is depleted of glucose and glycogen supply, so it turns to fat for energy fuel. And because fatty acids can't cross the BBB, it has to go through oxidation to be broken down first. Meanwhile, in liver, OAA is depleted for gluconeogenesis so acetyl-CoA accumulates. I guess my question is that why can't acetyl-CoA be delivered to other tissues directly but must be converted into ketone bodies first, where they will be converted back anyway. Does it have to do with the way acetyl-CoA transports in blood? I also read somewhere the reason could be to free up the CoA for more beta oxidation in liver? Thanks!

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[rafterman]

I've searched through the forum and still couldn't quite find a certain answer. I understand in the starvation state, body is depleted of glucose and glycogen supply, so it turns to fat for energy fuel. And because fatty acids can't cross the BBB, it has to go through oxidation to be broken down first. Meanwhile, in liver, OAA is depleted for gluconeogenesis so acetyl-CoA accumulates. I guess my question is that why can't acetyl-CoA be delivered to other tissues directly but must be converted into ketone bodies first, where they will be converted back anyway. Does it have to do with the way acetyl-CoA transports in blood? I also read somewhere the reason could be to free up the CoA for more beta oxidation in liver? Thanks!

I'm not certain that this is the correct answer, but just what intuition is telling me, the acetyl group of acetyl-CoA is small, the Coenzyme A (CoA) group is gigantic with all kinds of nasty polar groups and charges i.e. not going through membrane.

https://upload.wikimedia.org/wikipedia/commons/thumb/e/e9/Coenzym_A.svg/2000px-Coenzym_A.svg.png

I would assume that this cannot cross a membrane without a carrier protein. The ketone bodies have carbonyls in them, which help with the crossing of membranes. Body probably does ketogenesis to allow the ketone bodies to flux out of the liver and into the blood.

 

[bluequestions]

Thank you!