Ketones

Question 1

Concepts

Answer 1

Active hepatic FA beta ox drives ketogenesis (in mito). Synth in liver while its oxidation is extrahepatic. Activated by glucagon.

Question 2

Principles

Answer 2

Ketones with low pKa so soluble

1 rate limiting step = driven solely by hepatic beta ox

Question 3

Origin

Answer 3

Source = liver
Consumed = all mito but liver
Precursor = FA (add CH20 and 6 ketogenic AA's [Leucine and Lysine])

Question 4

Ketone Synth Points

Answer 4

1. 3 Acetyl-CoAs create acidic (pK=3.5) compound for global export
2. Mito CoASH retained for reuse
3. B-OH-Butyrate dehydrogenase for D-isomers only
4. In plasma - spont decarb creates volatile Acetone (also a trans ketone and resp for Diabetes fruit breath)

Question 5

Ketone Synth Reg

Answer 5

Limiting step = HMG-CoA Synthase (not allo)

Question 6

Nad/Nadh ratio

Answer 6

Maintained by acetoacetate reduction to B-OH-But via NADH

Question 7

Ketone synth Draw

Answer 7

On paper

Question 8

Ketone as fuel users

Answer 8

Muscle, heart, brain, kidney, 10-12 ATPs = Acetyl CoA, liver and RBC excluded, used in fetus

Question 9

Ketone as fuel path

Answer 9

1. B-OH-But enters and oxidized
2. Succinyl CoA donates CoA to activate acetoacetate transferase (not in liver)
3. B-ketothiolase to 2 Acetyl CoA’s
4. 2 Acetyl CoA and 1 OAA to 2 citrate in TCA

Question 10

Ketone as fuel Draw

Answer 10

On Paper

Question 11

Ctrl of Ketogenesis

Answer 11

No direct allosteric
Main Factors = Substrate (FA) avail; Induction of HMG CoA synthase (act by fast, fat diet = increased lipid catabolism)

Insulin def leads to increased lipid degradation