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2.1 Biochemistry of Metabolism > Sean - Ketone Bodies > Flashcards

Sean - Ketone Bodies Flashcards

1
Q

List the phases of metabolism during fasting as time progresses

A

Gastrointestinal (0-1)

Glycogenolysis (1-2)

Gluconeogenesis (2-7)

Ketosis (7+)

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2
Q

List in order the preferred energy sources as fasting progresses

A

Glucose

Glycogen

Fatty acids -> produce ketones

Proteins/amino acids

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3
Q

When are ketones produced

A

Ketone bodies are produced from fatty acids when liver glycogen is depleted

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4
Q

What type of fuel is preffered by the heart

A

Long chain fatty acids

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5
Q

How do fatty acids circulate in blood

A

Bound to albumin

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6
Q

What are fatty acids broken down into

A

Oxidised to CO2 and H2O

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7
Q

The use of fatty acids by the liver provides energy for what two processes?

A

Gluconeogenesis

Ureagenesis

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8
Q

Why is synthesis of ketones important?

A

Ketone synthesis further reduces the need for glucose utilisation (brain needs this)

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9
Q

Name three ketone bodies
(DRAW THESE)

A

Acetone

Acetoacetate

D-B-hydroxybutyrate

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10
Q

What happens to the ketone acetone?

A

Its exhaled from the body

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11
Q

What happens to the ketone acetoacetate?

A

Energy source for tissues such as skeletal and heart muscle and the renal cortex

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12
Q

What happens to D-B-Hydroxybutyrate?

A

Energy source for skeletal muscle, heart muscle, renal cortex

AND

Used as fuel by brain under starvation conditions (last resort)

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13
Q

How much of your daily energy intake is used by the brain?

A

20%

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14
Q

Can the brain use fatty acids as a fuel source?

A

NO

Only glucose or B-hydroxybutyrate ketone

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15
Q

Describe how much of energy for the brain is produced by ketone bodies after 3 days and 40 days

A

After 3 days of fasting = 25% of energy is from ketone

After 40 days of fasting = 70% is from ketones

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16
Q

What is ketosis

A

The overproduction of ketone bodies

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17
Q

What two things can cause ketosis

A

Diabetes mellitus

Low carb diets

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18
Q

How does diabetes cause ketosis

A

This is because the hepatocytes cannot take up glucose as a fuel

Acetyl-CoA accumulates in the hepatocytes and are converted into ketone bodies

Concentrations of ketones acetoacetate and D-B-hydroxybutyrate lower blood pH (acidosis)

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19
Q

What can acidosis lead to?

A

Coma
Death

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20
Q

Comment on the ketone levels in untreated diabetics

A

Can be 60x the normal concentrations

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21
Q

List some side effects of ketosis

A

Diarrhea

Constipation

Headaches

Thirst

Dizziness

Nausea

Lack of energy

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22
Q

How does the body deal with ketosis
(3)

A

Body tries to remove ketones via urine

Causes further removal of eater and electrolytes

Results in potentially fatal dehydration, tachycardia, hypotension

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23
Q

What is ketogenesis

A

The formation of ketone bodies in the liver mitchondria

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24
Q

What are ketones formed from?

A

Formed from acetyl CoA produced by B oxidation of fatty acids

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25
Q

When can fatty acids be metabolised in the liver

A

When the TCA cycle is not functioning

i.e. when components of TCA have been cannibalised to generate amino acids/nucleotides (starvation -> no glucose for TCA)

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26
Q

List the events that occur during starvation

A

Gluconeogenesis kicks in -> steals oxaloacetate from citric acid cycle to generate glucose

Acetyl-CoA accumulates as fatty acids undergo b oxidation

Citric acid cycle slows -> acetyl CoA is directed to ketone body formation instead of citric acid cycle

Ketone bodies are generated in the liver

Ketone bodies transported to regions in need of energy

Ketones reconverted into acetyl CoA to produce energy

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27
Q

What is the first step of ketogenesis?

A

Two molecules of acetyl CoA react together to form acetoacetyl CoA

Thiolase enzyme catalyses the reaction

28
Q

What catalyses the formation of acetoacetyl CoA

A

Thiolase

29
Q

What is the second step of ketogenesis?

A

Acetoacetyl CoA undergoes condensation in the presence of Acetyl CoA + H2O

Forms HMG CoA (and CoA-SH)

Catalysed by HMG CoA synthase

30
Q

What is HMG CoA?

A

B-Hydroxy-B-methylglutaryl-CoA

31
Q

What catalyses the formation of B-Hydroxy-B-methylglutaryl-CoA?

A

HMG CoA synthase

32
Q

What is the third step of ketogenesis?

A

HMG-CoA is cleaved by HMG CoA lyase

Forms acetoacetate (ketone) and acetyl CoA

33
Q

What enzyme cleaves HMG CoA?

A

HMG CoA lyase

34
Q

What is the fourth step of ketogenesis?
(2)

A

Acetoacetate is dehydrogenated to B-hydroxybutyrate

Catalysed by B-hydroxybutyrate dehydrogenase in the presence of NADH + H+

35
Q

What catalyses the formation of B-hydroxybutyrate?

A

B-hydroxybutyrate dehydrogenase

36
Q

What is the fifth step in ketogenesis?

A

Acetoacetate and B-hydroxybutyrate are transported across the mitochondrial membrane and the plasma membrane of the liver cells

They can now enter the blood stream to be used as a fuel by other cells of the body

37
Q

Where is acetoacetate and B-hydroxybutyrate transported across?

A

Mitochondrial membrane

Plasma membrane

38
Q

What is the sixth step of ketogenesis?

A

Small amounts of acetoacetate are decarboxylated to acetone in the blood stream

Catalysed by acetoacetate decarboxylase

39
Q

What catalyses the formation of acetone?

A

Acetoacetate decarboxylase

40
Q

Other than via ketogenesis, how can acetone be formed?

A

The spontaneous decarboxylation of acetoacetate

41
Q

List the molecules of ketogenesis

A

2 Acetyl-CoA
Acetoacetyl-CoA
HMG-CoA
Acetoacetate
B-hydroxybutyrate
Acetoacetate
Acetone

42
Q

List the enzymes of ketogenesis

A

Thiolase

HMG-CoA synthase

HMG-CoA lyase

D-B-hydroxybutyrate dehydrogenase

Acetoacetate decarboxylase

43
Q

What is acetone at standard pressure/temp?

A

A gas

44
Q

How is acetone treated by the body?

A

Treated as a waste product

It dissolves in blood stream and is exhaled

If someone has high ketone bodies then acetone can be smelt in breath or urine

45
Q

What is the regulatory enzyme of ketogenesis?

A

HMG CoA synthase

46
Q

What activates HMG CoA synthase

A

Increased fatty acids in the blood

47
Q

What inactivates HMG CoA synthase

A

Inhibited by high levels of CoASH

48
Q

How does high levels of CoASH activates/inhibit HMG CoA synthase?

A

When fatty acids are taken to liver, CoASH is used to activate them

Therefore, low CoASH indicate high fatty acids and therefore HMG CoA is activated

High CoASH indicates low fatty acids and therefore HMG CoA synthase is inhibited

49
Q

What is ketolysis?

A

The complete oxidation of ketone bodies to CO2 and water

The use of ketones by the body

50
Q

Where does ketolysis occur?

A

The mitochondria of extrahepatic tissues

51
Q

Why does ketolysis occur in the mitochondria of extrahepatic tissues?

A

Due to the high activity of the enzyme B-ketoacyl-coA transferase

52
Q

Why does ketolysis not occur in the liver

A

Due to a deficiency of B-ketoacyl-CoA transferase

53
Q

What ketone produced by fatty acids can not be broken down in ketolysis?

A

Acetone

54
Q

What is the fuel produced by ketolysis?

A

Acetyl CoA

55
Q

What enzymes are used in ketolysis?

A

Thiolase

B-hydroxybutyrate dehydrogenase

Enzyme-B-ketoacyl-CoA transferase

56
Q

What energy carrier is used in ketolysis (and produced in ketogenesis)?

A

NAD+

57
Q

What is the first step in ketolysis?

A

B-hydroxybutyrate is dehydrogenated

This forms acetoacetate

Catalysed by B-hydroxybutyrate dehydrogenase

58
Q

What catalyses the formation of acetoacetate in ketolysis?

A

B-hydroxybutyrate dehydrogenase

59
Q

What is the second step of ketolysis?

A

Acetoacetate is activated, forming acetoacetyl CoA

Catalysed by B-ketoacyl Co A transferase/ Succinyl CoA acetoacetate CoA transferase

Requires the conversion of succinyl CoA to succinate

60
Q

What catalyses the formation of acetoacetyl CoA?

A

Succinyl CoA acetoacetate CoA transferase

ALSO CALLED

B-ketoacyl-CoA transferase

61
Q

What is the second method of forming acetoacetyl CoA (without succinyl CoA)?
(4)

A

Acetoacetate is converted to acetoacetyl CoA

Requires ATP

Must be in the presence of CoA SH

Catalysed by thiokinase/ acetoacetyl CoA synthetase

62
Q

What is the third reaction in ketolysis?

A

Acetoacetyl CoA is converted to 2 Acetyl CoA

Catalysed by thiolase

63
Q

What happens to the 2 acetyl-CoA produced by ketolysis?

A

They enter the citric acid cycle

64
Q

How much ATP is produced by the 2 acetyl-CoA produced in ketolysis

A

20 ATP

65
Q

Other than acetyl-CoA, what product of ketolysis can be used to make energy?

A

B-hydroxybutyrate can be converted back into acetoacetate

This generates 1 NADH

This provides an additional 2.5 ATP after entering electron transport chain

66
Q

What is the total ATP production by ketolysis?

A

22.5 ATP

67
Q

What effect can ketones have on epilepsy?

A

Elevated ketone bodies in blood can lead to a reduction in the frequency of epileptic seizures

2.1 Biochemistry of Metabolism (21 decks)

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