Ketones Flashcards
Explain how fasting/starvation may cause a build up in ketone bodies?
- Fatty acids are transported to liver to be broken down during fasting
- Fatty acids -> Acetyl-CoA
- Increased acetyl-CoA exceeds capacity of TCA cycle
- Acetyl-CoA then shunted towards ketone bodies
What do 2 molecules of Acetyl CoA make?
Acetoacetyl-CoA (first step of ketone synthesis)
What is acetoacetyl-CoA converted into in the ketone synthesis pathway?
HMG-CoA
What is HMG-CoA converted into in the ketone synthesis pathway?
Acetoacetate
What 2 molecule is aceoacetate converted into in ketone body synthesis?
- Acetone (not used for fuel)
- 3-Hydroxybutarate
How is acetone excreted?
Through the lungs
- Fruity smell
What organs mainly use ketones?
- Muscle
- Heart
Spares glucose for brain
What organ cannot use ketone bodies?
Liver
What are all the molecules involved/steps of ketone body synthesis?
- 2x Acetyl-CoA
- 1 Acetoacetyl-CoA
- HMG-CoA
- Acetoacetate
- Acetone + 3-Hydroxybutarate
What ketone cannot be used as fuel?
Acetone (3-Hydroxybutyrate is)
What are the molecules/ steps of ketolysis?
- 3-Hydroxybutyrate (+ NAD= -> NADH)
- Acetoacetate
- Acetoacetyl CoA
- > 2x Acetyl-CoA
What energy source can the brain not use?
Fatty acids
How does the brain indirectly use fatty acids for energy?
- Fatty acids broken down to ketone bodies in liver
- Brain can use ketones -> convert into Acetyl-CoA
What is the pKa value of ketone bodies?
Low - therefore it is a strong acid
- Releases H+ at plasma pH
What kind of metabolic acidosis do ketones cause?
Anion gap metabolic acidosis
What is the first step of the TCA cycle?
Oxaloacetate + Acetyl-CoA
-> Citrate
Why is oxaloacetate converted to malate in diabetes?
- Fatty acid oxidation produces NADH, causing Oxaloacetate to be converted to Malate (reversible step)
Why is Oxaloacetate low in diabetes?
This stalls TCA cycle
- Oxaloacetate is being converted to Glucose
- Fatty acid oxidation produces NADH, causing Oxaloacetate to be converted to Malate (reversible step)
What happens to acetyl coA as a result of low oxaloacetate and thus a stalling of the TCA cycle?
Shunted to Ketones
- Causes DKA
What does increased NADH result in in terms of oxaloacetate?
Causes Oxaloacetate to be depleted and converted into Malate
- Does not go into TCA cycel
What enzyme converts Malate to oxaloacetate and vice versa?
Malate dehydrogenase
How can alcoholism cause ketosis?
Ethanol metabolism causes an increase in NADH
- NADH favors oxaloacetate to Malate, depleting Oxaloacetate
- Acetyl-CoA does not go to TCA cycle as there is no oxaloacetate to bind to
- Acetyl-CoA shunted to ketones
How can alcoholics get hypoglycemia?
Increased NADH favors Oxaloacetate -> Malate
- Oxaloacetate depleted
- Oxaloacetate used for gluconeogenesis
What are the different causes of elevated urine ketones?
- Poorly controlled diabetes
- DKA
- Prolonged starvation
- Alcoholism
