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POM 2 Cell biology > 2.7 Integration Of Metabolism > Flashcards

2.7 Integration Of Metabolism Flashcards

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1
Q

What forms of energy production does skeletal muscle rely on?

A

Fatty acid oxidation and carbohydrate oxidation

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2
Q

During light contraction of skeletal muscle, how is ATP consumption met?

A

Through oxidative phosphorlyation

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3
Q

During vigorous contraction, how is ATP consumption met?

A

Muscle stores of glycogen are then broken down to produce ATP

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4
Q

Under anaerobic conditions, what is pyruvate converted into?

A

Lactate

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5
Q

What is the only substrate that the brain can use as a source of energy?

A

Glucose/carbohydrates

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6
Q

Which energy source can the brain not use?

A

The brain cannot metabolise fatty acids

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7
Q

What can partially substitute for glucose in the brain?

A

Ketone bodies

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8
Q

What can too little glucose in the brain cause?

A

Hypoglycaemia - faintness and coma

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9
Q

What can too much glucose in the brain cause?

A

Hyperglycaemia - irreversible damage to multiple organ systems like retinas

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10
Q

What does the heart utilise for energy substrates?

A

TCA cycle substrates – free fatty acids and ketone bodies

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11
Q

What happens to the heart when energy demand > energy supply?

A

Myocardial infarction

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12
Q

Name four fuel sources for the heart

A

Ketone bodies, glucose, fatty acids and lactate

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13
Q

Why does the heart have a lot of mitochondria?

A

Because the heart is designed for aerobic conditions – high energy supply

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14
Q

How does the liver store glucose?

A

As glycogen

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15
Q

What range does the liver try keep the blood glucose levels between?

A

4-5.5 mmol/L

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16
Q

Excess of what can be used to generate glycogen in the liver and muscle?

A

Excess glucose-6-phosphate

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17
Q

How are fatty acids stored in adipose tissue?

A

They are stored as triglycerides in the adipose tissue

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18
Q

During fasting, what happens to the Acetyl CoA which is produced?

A

Much of the Acetyl CoA is used to generate ketone bodies

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19
Q

What happens to lactate production during periods of intense exercise?

A

It increases - produced from pyruvate

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20
Q

What three things can the body initially do when the blood glucose concentration drops below 3mM?

A
  • Breakdown liver glycogen stores to maintain levels
  • Release free fatty acids from adipose tissue
  • Convert Acetyl CoA into ketone bodies in the liver
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21
Q

How does the brain get more glucose when the body is in a hypoglycaemic coma?

A

The skeletal muscle can use ketone bodies and fatty acids

This makes more plasma glucose available for the brain which cannot metabolise fatty acids

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22
Q

After how many hours are the bodies glycogen stores depelated?

A

12-18 hours

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23
Q

After the body has depleted its glycogen stores, what is used to generate glucose?

A

Gluconeogenesis

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24
Q

How is pyruvate regenerated from lactate?

A

Using lactate dehydrogenase enzyme

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25
Q

Which reaction in gluconeogenesis occurs in the mitochondria?

A

The convertion of pyruvate to oxaloacetate

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26
Q

What enzyme is used to convert pyruvate into oxaloacetate?

A

Pyruvate carboxylase

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27
Q

How does oxaloacetate move out the mitochondria once it has been produced from pyruvate?

A

It moves via the malate shuttle, where it is then converted into phosphophenolpyruvate

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28
Q

How do glucogenic amino acids give rise to glucose?

A

They undergo deamination reactions which results in the production of pyruvate, which yields glucose through gluconeogenesis

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29
Q

Where do the reactions of gluconeogenesis occur?

A

Pyruvate to oxaloacetate in mitochondria
Rest in cytosol

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30
Q

List out all the reactions in gluconeogenesis

A

Pyruvate
Oxaloacetate by pyruvate carboxylase
Phosphoenolpyruvate by phosphoenolpyruvate carboxykinase
F-1,6-BP
F6P by fructose-1,6-bisphosphatase
G6P
Glucose by glucose-6-phosphatase

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31
Q

How is gluconeogenesis made energetically favourable?

A

The 4 additional high energy bonds make it energetically favourable

ΔG for the straight reversal of glycolysis would be +90 (unfavourable) but ΔG for gluconeogenesis is -38 kJ/mol

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32
Q

What do ketogenic amino acids give rise to?

A

Skeletons that can be used to synthesise FAs and ketone bodies but cannot enter gluconeogenesis

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33
Q

What happens to pyruvate during anaerobic respiration?

A

It is taken up by the liver and converted into lactate by LD to replenish NAD+ levels and maintain glycolysis

34
Q

In the fasting state, what is the main metabolic fuel for the heart?

A

Fatty acids

35
Q

In the fasting state, what is the main metabolic fuel for the brain?

A

Glucose

36
Q

In the fed state, why does insulin stimulate an increase in the number of glucose transporters on the adipocyte surface?

A

To facilitate glucose uptake to make triglycerides

37
Q

Why do plasma levels of ketone bodies increase as the fed state progresses into fasting and then starvation?

A

Ketone bodies are produced by the liver

38
Q

How can glucogenic amino acids be used as a fuel source?

A

The glucogenic amino acids’ skeletons can give rise to glucose via gluconeogenesis

39
Q

In the fasting state, glucagon acts to increase the synthesis of glucose from which molecules?

A

Glycogen, glycerol and amino acids

40
Q

What generates the bulk of the NADPH needed for anabolic pathways e.g. cholesterol synthesis?

A

Glucose-6-phosphate via the pentose phosphate pathway

41
Q

What are three non-carbohydrate precursors which enter into the gluconeogenic cycle?

A

Lactate, amino acids and glycerol

42
Q

What is the cori cycle?

A

The generation of pyruvate from lactate

43
Q

How does glycerol act as a non-carbohydrtae substrate for gluconeogenesis?

A

It is used to produced DHAP and enter the gluconeogenic pathway

44
Q

Which are the three reactions of gluconeogenesis which need to be bypassed through using kinase enzymes?

A

Phosphenolpyruvate to pyruvate
Fructose - 1,6 - Bisphosphate to Fructose - 6 - Phosphate
Glucose - 6 - Phosphate to Glucose

45
Q

What enzyme is used to convert Glucose - 6 - Phosphate into Glucose?

A

Glucose - 6 - Phosphatase

46
Q

What organs is Glucose - 6 - Phosphatase found in?

A

Liver and kidneys

47
Q

What are the seven molecules which deamination of all 20 amino acids gives rise to?

A 
Pyruvate
Oxaloacetate
Succinyl CoA
Fumerate
Acetyl CoA
Acetoacetyl CoA
Alpha-ketoglutarate
48
Q

What happens to the rest of the amino acid once it has been broken down by deamination?

A

Remaining compounds are excreted in the urea

49
Q

Which tissues can use ketone bodies as an energy source?

A

Muscle and brain

50
Q

What happens to the glucose transporters on the membranes of muscle cells as the muscle contracts?

A

The number present on the membranes of the muscle cells increases

51
Q

What three effects does adrenaline have on helping the cell meet the adequate demands for ATP?

A

Increases the rate of glycolysis in muscle
increases th rate of gluconeogenesis in liver
Increases the release of fatty acids from adipocytes

52
Q

What causes an increase in muscle glycolysis, gluconeogenesis and fatty acid breakdown during exercise?

A

The release of adrenaline

53
Q

During anaerobic conditions what happens to the glycogen in the muscle?

A

It is broken down

54
Q

What is the name of the pathway given to the breakdown of glycogen into glucose?

A

Glycogenolysis

55
Q

What triggers glycogenolysis?

A

Glucagon

56
Q

How is the Cori cycle used in anaerobic conditions?

A

Pyruvate is taken up by the liver and converted into lactate using lactate dehydrogenase

The replenished NAD+ levels allows glycolysis to continually occur

57
Q

What does insulin do?

A

Stimulates the uptake and use of glucose, and storage of glycogen and fat

58
Q

What enzymes catalyses the first, irreversible step of glycolysis?

A

Hexokinase

59
Q

What are the two different isoforms of hexokinase found in the muscle and the liver?

A

Hexokinase I is found in muscle
Hexokinase IV is found in the liver

60
Q

What is the Michaelis constant?

A

The concentration of substrate at which an enzyme functions at half-maximal rate (Vmax)

61
Q

What is the Km of Hexokinase I and what does it mean?

A

0.1 mM

This means it is active at very low concentrations of glucose and thus operates at maximum velocity at all times

62
Q

Which hexokinase is sensitive to inhibition by product glucose - 6 - phosphate?

A

Hexokinase I

63
Q

What are the four changes which occur during aerobic exercise?

A
  1. Increase in number of glucose transporters in muscle
  2. Increase glycolysis in muscle
  3. Increase gluconeogenesis in liver
  4. Increased beta oxidation to make Acetyl CoA which is the used to generate ATP
64
Q

Where does the convertion of lactate into pyruvate occur?

A

IN the liver

65
Q

During the fasted state, the transamination reactions of amino acid are an important substrate for what process?

A

Gluconeogenesis

66
Q

During anaerobic conditions, why is hexokinase I Inhibited?

A

During anaerobic conditions, glycolysis slows

Glucose concentration drops but hexokinase I is still active because of its low Km, thus glucose is converted into G6P

Thus G6P accumulates which inhibits hexokinase I

67
Q

Where is Hexokinase IV found?

A

In the liver

68
Q

What does Hexokinase IV do?

A

Converts glucose into glucose-6-phosphate in the liver

69
Q

What is the KM of Hexokinase IV?

A

4

70
Q

What does the KM value of Hexokinase IV indicate?

A

4 - only active at very high concentrations of glucose

71
Q

Which hexokinase enzyme is more sensitive to G-6-P inhibition?

A

Hexokinase I

72
Q

What occurs straight after a meal has been consumed?

A

Insulin is secreted and glucagon drops, causing:
* increased glucose uptake by liver for glycogenesis and glycolysis where acetyl CoA produced is used for lipogenesis
* increased glucose uptake and glycogenesis in muscle
* increased triglyceride synthesis in adipose tissue
* increased metabolic intermediate usage

73
Q

What happens after a period of fasting following a meal?

A

Glucose has been all stored as glycogen so blood glucose levels start to drop

  • This triggers glucagon secretion
  • Glucagon triggers glycogenolysis, and gluconeogenesis
  • Beta oxidation occurs – fatty acids become an alternative substrate for ATP to preserve glucose for the brain
74
Q

What happens after prolonged fasting?

A
  • Glycogen stores have all been used up, so gluconeogenesis dominates
  • Proteolysis also occurs to make amino acids that can undergo deamination reactions to make pyruvate - used in gluconeogenesis
75
Q

Why does triglyceride hydrolysis increase during periods of prolonged fasting?

A

The triglycerides are broken down into glycogen and fatty acids
Fatty acids used in beta-oxidation to make ATP substrates (acetyl CoA)
Glycogen can assist with gluconeogenesis, enters as DHAP

76
Q

Why does ketone body synthesis occur during periods of prolonged fasting?

A

During fasting, gluconeogenesis is occuring

This means all oxaloacetate is being used up

Therefore, there may be an excess of Acetyl CoA

The excess Acetyl CoA is used to produce ketone bodies through ketogenesis

77
Q

How does diabetic ketoacidosis occur?

A

The body does not produce enough insulin, therefore glucose cannot be stored in cells, body relies on fats for energy

Fatty acids are broken down into ketone bodies

78
Q

What happens to the insulin : glucagon ration after periods of prolonged fasting?

A

Increases further

79
Q

Which cells of the islets is glucagon released from?

A

Alpha cells

80
Q

What two processes does glucagon stimulate in the liver?

A

Glycogenolysis and gluconeogenesis

81
Q

What are glucocorticoids?

A

Steroid hormones which increase synthesis of metabolic enzymes concerned with glucose availability

82
Q

Wh are ketone bodies produced after periods of prolonged fasting?

A

Ketone bodies are produced from fatty acids and amino acids in liver to substitute partially the brain’s requirement for glucose

POM 2 Cell biology (15 decks)

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