Ketones

Question 1

Explain how fasting/starvation may cause a build up in ketone bodies?

Answer 1

• 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

Question 2

What do 2 molecules of Acetyl CoA make?

Answer 2

Acetoacetyl-CoA (first step of ketone synthesis)

Question 3

What is acetoacetyl-CoA converted into in the ketone synthesis pathway?

Answer 3

HMG-CoA

Question 4

What is HMG-CoA converted into in the ketone synthesis pathway?

Answer 4

Acetoacetate

Question 5

What 2 molecule is aceoacetate converted into in ketone body synthesis?

Answer 5

• Acetone (not used for fuel)

- 3-Hydroxybutarate

Question 6

How is acetone excreted?

Answer 6

Through the lungs

- Fruity smell

Question 7

What organs mainly use ketones?

Answer 7

• Muscle
• Heart
  Spares glucose for brain

Question 8

What organ cannot use ketone bodies?

Answer 8

Liver

Question 9

What are all the molecules involved/steps of ketone body synthesis?

Answer 9

• 2x Acetyl-CoA
• 1 Acetoacetyl-CoA
• HMG-CoA
• Acetoacetate
• Acetone + 3-Hydroxybutarate

Question 10

What ketone cannot be used as fuel?

Answer 10

Acetone (3-Hydroxybutyrate is)

Question 11

What are the molecules/ steps of ketolysis?

Answer 11

• 3-Hydroxybutyrate (+ NAD= -> NADH)
• Acetoacetate
• Acetoacetyl CoA
• > 2x Acetyl-CoA

Question 12

What energy source can the brain not use?

Answer 12

Fatty acids

Question 13

How does the brain indirectly use fatty acids for energy?

Answer 13

• Fatty acids broken down to ketone bodies in liver

- Brain can use ketones -> convert into Acetyl-CoA

Question 14

What is the pKa value of ketone bodies?

Answer 14

Low - therefore it is a strong acid

- Releases H+ at plasma pH

Question 15

What kind of metabolic acidosis do ketones cause?

Answer 15

Anion gap metabolic acidosis

Question 16

What is the first step of the TCA cycle?

Answer 16

Oxaloacetate + Acetyl-CoA

-> Citrate

Question 17

Why is oxaloacetate converted to malate in diabetes?

Answer 17

• Fatty acid oxidation produces NADH, causing Oxaloacetate to be converted to Malate (reversible step)

Question 18

Why is Oxaloacetate low in diabetes?

This stalls TCA cycle

Answer 18

• Oxaloacetate is being converted to Glucose

- Fatty acid oxidation produces NADH, causing Oxaloacetate to be converted to Malate (reversible step)

Question 19

What happens to acetyl coA as a result of low oxaloacetate and thus a stalling of the TCA cycle?

Answer 19

Shunted to Ketones

- Causes DKA

Question 20

What does increased NADH result in in terms of oxaloacetate?

Answer 20

Causes Oxaloacetate to be depleted and converted into Malate
- Does not go into TCA cycel

Question 21

What enzyme converts Malate to oxaloacetate and vice versa?

Answer 21

Malate dehydrogenase

Question 22

How can alcoholism cause ketosis?

Answer 22

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

Question 23

How can alcoholics get hypoglycemia?

Answer 23

Increased NADH favors Oxaloacetate -> Malate

• Oxaloacetate depleted
• Oxaloacetate used for gluconeogenesis

Question 24

What are the different causes of elevated urine ketones?

Answer 24

• Poorly controlled diabetes
• DKA
• Prolonged starvation
• Alcoholism