MMT: ketone bodies Flashcards

1
Q

What are the three main ketone bodies?

A

Acetoacetate, acetone, and b-hydroxybutyrate

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2
Q

Describe ketone bodies.

A

A soluble fuel made by the liver during the fasting state that the brain can use

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3
Q

Describe liver metabolism during prolonged fasting.

A

b-oxidation is ramped up to produce acetyl CoA that can be used for gluconeogenesis as well as ketone body synthesis

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4
Q

Where does ketone body production occur?

A

Mitochondria in the liver

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5
Q

What are the major enzymes in synthesis of ketone bodies?

A
  1. Thiolase
  2. HMG CoA synthase (mitochondrial enzyme)
  3. HMG CoA lyase
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6
Q

What are the major intermediates in synthesis of ketone bodies?

A
  1. Acetoacetyl CoA
  2. HMG CoA
  3. Acetoacetate
  4. Acetone
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7
Q

What is the most prevalent ketone body? What is significant about this?

A

b-hydroxybutyrate; oxidation of it produces an extra NADH, making it energy dense

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8
Q

Where are ketone bodies oxidated?

A

Muscle and other tissues such as the brain

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9
Q

What are the intermediates of oxidation of ketone bodies?

A
  1. B-hydroxybutyrate
  2. Acetoacetate
  3. Acetoacetyl CoA
  4. 2 acetyl CoA
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10
Q

What are the enzymes of oxidation of ketone bodies?

A
  1. b-hydroxybutyrate dehydrogenase
  2. succinyl CoA acetoacetate CoA transferase
  3. thiolase
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11
Q

Which step of ketone oxidation produces NADH?

A

First one! B-hydroxybutyrate to acetoacetate

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12
Q

Why does oxidation of ketones not occur in the liver?

A

To ensure formed ketone bodies are not just immediately oxidized in the liver, there is a lack of the enzyme succinyl CoA acetoacetate CoA transferase

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13
Q

What is the energy yield of ketone bodies?

A

21.5 ATP

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14
Q

Where is the energy cost in ketone oxidation?

A

Activation of acetoacetate; it requires consumption of succinyl CoA, reducing formation of one GTP in the TCA cycle

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15
Q

How does insulin regulate ketogenesis?

A

An absence of insulin increases CPTI which decreases malonyl CoA; this results in upregulation of acetyl CoA production. In excess, acetyl CoA will become ketone bodies

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16
Q

What are regular ketone body concentrations during prolonged fasting?

A

3-5 mM

17
Q

In untreated type I diabetes, what is the ketone body concentration?

A

Up to 20 mM

18
Q

Describe why ketone bodies are in high concentrations in untreated diabetes.

A

Insulin is absent, resulting in liver cells responding as if the body is starving even when it is not. This upregulates ketogenesis

19
Q

Describe diabetic ketoacidosis.

A

An acute, life-threatening complication of diabetes that occurs in type I diabetes. It is caused by a response to insulin deficiency that results in high ketogenesis and excess acetone production

20
Q

How does an insulin deficiency impact lipolysis?

A

It will increase it! More fatty acids will transport to hepatocytes for use and then more ketoacids are formed

21
Q

Describe CPTII deficiency.

A

An issue with energy production that results in muscle pain and myoglobinuria after exercise. Causes hypokinetic hypoglycemia, cardiomyopathy, liver failure

22
Q

What is a major presentation of CPTII deficiency?

A

Hypoketotic hypoglycemia