Week 5: Ketogenesis Flashcards
What is ketogenesis
biosynthesis of ketone bodies
Where does ketogenesis occur?
Liver
When does ketogenesis occur?
after about 2-4 days reduces gluconeogenesis
Theoretically starts with glucagon signaling but after 2-4 days acetoacetate and β-hydroxybutarate simultaneously rise
Problem with relying on ketones for long-term fasting
Ketones are Acids (-ate suffix) makes the blood more acidic lowering the pH
How are ketones generated
In the liver Acetyl-CoA is generated from FAs from adipose tissue due to glucagon signaling carried by albumin and transported into mitochondria by carnitine shuttle and undergoes β-oxidation
High [acetyl-CoA] inhibits pyruvate DH (TCA) and activates pyruvate carboxylase (gluconeogenesis)
2x acetyl-CoA -Thiolase-> Acetoacetyl-CoA
Acetoacetyl-CoA + Acetyl-CoA -HMG-CoA Synthase-> HMG-CoA (also a precursor for cholesterol synthesis but we are in a fasting state and this HMG-CoA is in the mitochondria, cholesterol is synthesized in the cytoplasm in the fed state)
HMG-CoA -HMG-CoA Lyase-> Acetoacetate + Acetyl-CoA
Acetoacetate is one of the ketones we are making
Acetoacetate + NADH –> β-hydroxybutyrate + NAD+
β-hydroxybutyrate and Acetoacetate are the ketones
Liver usage of ketones
Liver doesn’t have enzymes to use these molecules as fuel so they are for other tissues
Breakdown of Acetoacetate
acetoacetate -in the blood-> Acetone + CO2 This is what gives fruity sweet smell from someone in a ketoacidotic state
Breakdown of β-hydroxybutyrate
oxidized to return to acetoacetate
β-hydroxybutyrate + NAD+ –> Acetoacetate + NADH
Acetoacetate + Succinyl-CoA –> Acetoacetyl-CoA + Succinate
(USually done for protein synthesis but in a prolonged fast the GTP isn’t needed so the energy is used to reduce Acetoacetate Succinayl-CoA + GDP -Thiokinase-> Succnate + GTP (for protein synthesis)
(In the mitochondria) Acetoactyl-CoA + CoASH -Thiolase-> 2x Acetyl CoA which goes to the mitochondria to enter the TCA cycle
