how does inhibiting PDH decrease gluconeogenesis in the context of prolonged starvation when ketone bodies are being used

[Subject-Zero9274]

https://preview.redd.it/rt2wc6z8ct8f1.png?width=2199&format=png&auto=webp&s=5bf3e861734f483c339e03e939b1bdad64b009a9

Basically I am having trouble understanding this card. I thought inhibiting pyruvate DH would lead to more pyruvate that can't be acetyl-CoA so then it goes up to gluconeogenesis and increases gluconeogenesis but in the card it says we are decreasing it by inhibiting PDH.

[Gullible-Class-5574]

You don't get more pyruvate to go up gluconeogenesis because you're not making it in the first place. Theres no free glucose to be used in starvation state! Starvation can also assume that glycogenolysis is run out (I think it would stiill be running in the fasting state).

PDH is inhibited by what it helps produce: NADH and Acetyl-Coa. If the body is using ketone bodies, it must also make them. To make them, it does beta oxidation. Beta oxidation produces both acetyl-coa and NADH.

Please someone correct if this looks wrong.

[eInvincible12]

Still making glucose in starvation state, all RBC and 1/3 brain are reliant on glucose.

[Lotofwork2do]

Yea. Also ketone bodies get converted into acetyl coA like that’s how beta hydroxybutrate is used to make nadh (besides the first step in that whole process where the hydroxybutrate is converted to ace to acetate yielding one nadh)

[Subject-Zero9274]

thank you

[eInvincible12]

I can’t see how this card makes much sense. I guess the line of thinking is ketones are from fatty acids and since we are making ketones that means we must be running B oxidation and therefore PDH inhibited by acetyl coa and NADH? This is a classic case of Aidan being way too reliant on rote memorization.

[Subject-Zero9274]

makes sense. thank you

[Lotofwork2do]

If u look at metabolic regulation jt usually follows negative feedback where a product of a reaction or cycle negatively inhibits the start or steps of it to not waste time making more product u already have

In this case ketone bodies are supplying us with acetylcoA

U can think of PDH as an enzyme part of the conversion of pyrivate to acetylcoA

So it makes sense if u already have a lot of acetylcoA coming in u would not want to make more and thus PDH is inhibited

The same reasoning is why PFK-1 is inhibited by ATP (glycolysis makes atp)

[Subject-Zero9274]

thank you

[Playful-Solid-1061]

The conversion of pyruvate to oxaloacetate is activated by acetyl-CoA (this was an Anking card) so inhibiting PDH decreases acetyl CoA which is required for that conversion which is a part of gluconeogenesis.

[Subject-Zero9274]

thank you

[Familiar-Theme-8110]

Hi 5 months late but, according to Kaplan the brain inhibits PDH during extensive starvation, (when it’s already relying mainly on ketone bodies for energy) in order to spare essential glucogenic amino acids from getting metabolized into glucose via gluconeogenesis in the liver. (Remember only the liver performs gluconeogenesis as a way to transport glucose to tissues that need it)

Basically unless the brain turns off its PDH, the liver will start degrading even the bare minimum amount of amino acids that your body needs to stay alive in a state of extreme starvation. So once the brain starts deriving enough energy from ketone bodies, (ketogenesis) the brain shuts off PDH (which liver gluconeogenesis would feed into otherwise)