Glucose Metabolism in Physiological and Pathological Conditions Flashcards

1
Q

How does glucose cross the cell membrane?

A

Facilitated diffusion via glucose transporters

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2
Q

Which tissues express GLUT1?

A

Foetal tissue

Cancer cells

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3
Q

Which tissues express GLUT2?

A

Liver
Kidney
Intesting
Pancreatic beta-cell

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4
Q

Which tissues express GLUT3?

A

Brain

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5
Q

Which tissues express GLUT4?

A

Muscle

Adipose tissue

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6
Q

What do glucose transporters depend on for the transport of glucose?

A

Availability of glucose in extracellular compartment

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7
Q

What is the relationship between insulin and GLUT4?

A

Insulin receptor stimulation facilitates translocation of GLUT4 to cell membrane

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8
Q

What are most of the GLUT4 molecules in cell associated with?

A

GLUT4 storage vesicles (GSVs) in cytosol

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9
Q

Is GLUT3 activity under the control of insulin?

A

No, it’s always active

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10
Q

What is the activity of GLUT3 at different plasma glucose concentrations?

A

High activity at all plasma glucose concentrations

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11
Q

What is the relationship between an enzyme’s Km value and its affinity for a substrate?

A

Low Km = high affinity

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12
Q

Why does GLUT3 have such a low Km?

A

Because needs to operate at full capacity regardless of plasma concentration because brain needs to work all the time

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13
Q

Why does GLUT4 have a moderate Km?

A

Needs to work well at higher plasma concentrations because body needs to store extra glucose at those times

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14
Q

Why does GLUT2 have such a high Km?

A

Glucose in hepatic portal vein can reach very high concentration after meal
Liver only takes up glucose for storage when its in plentiful supply

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15
Q

What is glucose intolerance in part attributed to?

A

Impaired glucose uptake by GLUT4

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16
Q

What are the blood glucose and GLUT4 levels in non-diabetics?

A

Maintain blood glucose levels

GLUT4 fluctuates

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17
Q

How do blood glucose levels change in people with diabetes?

A

Always high

Fluctuate a lot

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18
Q

Which tissues express enzymes for glycogenolysis?

A

Liver
Muscle
Kidney cortex

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19
Q

What is the role of glycogenolysis in muscle?

A

Sustain muscular activity

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20
Q

What is the role of glycogenolysis in the liver and kidney cortex?

A

Maintain blood glucose concentration

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21
Q

Which enzyme does muscle lack that disallows it from contributing to blood glucose maintenance via glycogenolysis?

A

Glucose-6-phosphatase

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22
Q

Which cells express enzymes for glycogenolysis in hypoxic conditions?

A

Astrocytes

Tumour cells

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23
Q

What is a neurovascular unit?

A

Blood capillary
Astrocyte
Neuron

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24
Q

What is the role of astrocytes in glucose metabolism?

A

Astrocytes take up glucose from capillary > store as glycogen

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25
Q

Why do astrocytes store glycogen?

A

Critical to protection of neurons in ischaemic stroke > still have source of glucose

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26
Q

What are the bonds in glycogen between glucose monomers?

A

Alpha-1,4-glycosidic linkage

Alpha-1,6-glycosidic linkage

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27
Q

Breaking which bond in glycogen gets the most amount of glucose?

A

Alpha-1,4-glycosidic linkage

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28
Q

What is a rate limiting step?

A

Catalyses irreversible reaction

Can be regulated

29
Q

What is the enzyme involved in the rate-limiting step of glycogen breakdown?

A

Phosphorylase

30
Q

What is UDP-glucose?

A

Activated glucose

31
Q

What does UDP-glucose phosphorylase do?

A

Catalyses reversible reaction

Activates glucose

32
Q

What is the rate-limiting enzyme in glycogen synthesis?

A

Glycogen synthase

33
Q

What is the relationship between phosphorylase and glycogen synthase?

A

Inhibiting one activates the other

34
Q

What are the fates of glucose-1-phosphate from glycogen?

A

Converted to glucose-6-phosphate
Used in
- Hypoxic tumour cells > pentose phosphate pathway
- Liver and kidney > glucose
- Muscle and tumour cells > energy
- Astrocytes > lactate > pyruvate in neurons

35
Q

What are the liver and kidney specialised to do in terms of glucose metabolism?

A

Glucose producers

36
Q

What are muscle and other organs specialised to do in terms of glucose metabolism?

A

Glucose utilisers

37
Q

What is the function of glycolysis in muscles?

A

Generate ATP for muscle contraction

38
Q

What is the function of glycolysis in the liver?

A

Generate acetyl-CoA for fatty acid synthesis

39
Q

What is the function of liver and kidney cortex gluconeogenesis?

A

Generate glucose to maintain blood glucose levels

40
Q

What is the difference between glucokinase and hexokinase?

A

Same enzyme
Called glucokinase in liver and kidney
Called hexokinase in other tissues

41
Q

What are the rate limiting enzymes in glycolysis and glycogen breakdown?

A

1) (Glycogen) phosphorylase
2) Glucokinase/hexokinase
3) Phosphofructose kinase-1 (PFK-1)
4) Pyruvate kinase

42
Q

What limits glycolysis?

A

Shortage of NAD

43
Q

Where is the majority of NAD located?

A

In mitochondria > not available for glycolysis in cytosol

44
Q

How is glycolysis sustained in anaerobic conditions?

A

NAD generated by lactate dehydrogenase-catalysed reaction

45
Q

What does lactate dehydrogenase do?

A

Reduce pyruvate to lactate to make NAD

46
Q

What happens to the lactate generated by lactate dehydrogenase?

A

Exported to liver
Liver converts to glucose
Glucose goes back to muscle for use

47
Q

Does lactate dehydrogenase catalyse a reversible or irreversible reaction?

A

Reversible

48
Q

What are the rate limiting enzymes of gluconeogenesis?

A

1) Glucose-6-phosphatase (G-6-Pase)
2) Fructo-1,6-bisphosphatase (FBPase-1)
3) Phosphoenolpyruvate carboxykinase (PEPCK)

49
Q

What are the precursors of gluconeogenesis, and what are their main sources?

A

Muscle > alanine
Muscle > lactate
Adipose tissue > glycerol

50
Q

What does adrenaline control in glucose metabolism in muscles, and why?

A

Stimulates glycogenolysis

To sustain muscular activity

51
Q

What does insulin control in glucose metabolism in muscles, and why?

A

Stimulates glycogen synthesis

Store glycogen for future use

52
Q

What does glucagon control in glucose metabolism in the liver and kidney cortex?

A

Stimulates glycogenolysis and gluconeogenesis
NOT glycolysis
To maintain blood glucose concentration

53
Q

What does insulin control in glucose metabolism in the liver and kidney cortex?

A

Stimulates glycogen synthesis and glycolysis

To store glucose as glycogen and fatty acid

54
Q

Where is adrenaline released from?

A

Adrenal medulla

55
Q

Where is insulin released from?

A

Pancreas

56
Q

Where is glucagon released from?

A

Pancreas

57
Q

What is the role of glucocorticoids in glucose metabolism?

A

Long-term

Anti-insulin activity

58
Q

What is the relationship between glucagon and insulin?

A

Reciprocally regulated

59
Q

What stimulates the release of insulin?

A

High blood glucose

60
Q

What stimulates the release of glucagon?

A

Low blood glucose

61
Q

Which metabolic pathways are involved in gluconeogenesis?

A

Cori cycle

Alanine cycle

62
Q

What is the Cori cycle?

A

Conversion of lactate from other tissues to glucose

63
Q

What is the alanine cycle?

A

Conversion of alanine from muscle to glucose

64
Q

Why can’t the citric acid cycle and electron transport chain supply enough ATP during rigorous muscular activity?

A

Limitation of O2 supply

65
Q

How does muscle generate energy during rigorous muscular activity?

A

Derive all ATP from glycolysis

Rapid degradation of glycogen

66
Q

Is glycolysis efficient?

A

No, only generates 2 ATP/glucose

67
Q

How does the muscle provide alanine to the liver?

A

Protein breakdown

Pyruvate from glycolysis converted

68
Q

How is alanine involved in the liver urea cycle?

A

Pyruvate + amino group > alanine (in muscle)
Carried to liver
Conversion to pyruvate liberates amino group > urogenesis > urea

69
Q

When is most to all of the body’s glycogen stores used up?

A

Prolonged fasting