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ESA2 - Metabolism, Endocrinology and Haematology > Energy Production - Carbohydrates and Glycolysis > Flashcards

Energy Production - Carbohydrates and Glycolysis Flashcards

1
Q

What is primary lactase deficiency caused by?

A

Absence of lactase persistence allele (occurs only in adults)

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2
Q

What is secondary lactase deficiency caused by?

A

Injury to small intestine eg gastroenteritis, coeliac disease, Crohn’s, ulcerative colitis

Occurs in both infact and adults, generally reversible

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3
Q

How is congenital lactase deficiency inherited?

A

Autosomal recessive

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4
Q

How is glucose taken into intestinal epithelial cells?

A

Active transport by SGLT1

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5
Q

How is glucose taken into the blood from intestinal epithelial ells?

A

GLUT2

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6
Q

Where are GLUT2 carriers found?

A

Kidney, liver, pancreatic beta cells, small intestine

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7
Q

Where are GLUT4 carriers found?

A

Adipose tissue, striated muscle

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8
Q

Which is the insulin regulated glucose transporter?

A

GLUT4

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9
Q

What cells have an absolute requirement for glucose?

A

Erythrocytes, neutrophils, innermost cells of kidney medulla, lens of the eye

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10
Q

Why do erythocytes have an absolute requirement for glucose?

A

No mitochondria so only get energy from glycolysis

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11
Q

Why do neutrophils have an absolute requirement for glucose?

A

Use mitochondria primarily for production of free radicals to kill pathogens as opposed to using them for respiration

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12
Q

Why do the innermost cells of the kidney medulla have an absolute requirement for glucose?

A

Kidney cortex uses a lot of oxygen so there’s not much oxygen left for the medulla

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13
Q

Why do cells in the lens of the eye have an absolute requirement for glucose?

A

Poor oxygen supply so get energy from glycolysis

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14
Q

True or False:

CNS (brain) prefers glucose as fuel but can use ketone bodies for some energy requirements in times of starvation

A

True

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15
Q

What are the two phases of glycolysis?

A

Investment and payback

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16
Q

What are the functions of glycolysis?

A

Oxidation of glucose, NADH production, synthesis of ATP, production of C6 and C3 intermediates

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17
Q

How many molecules of NADH are produced per molecule of glucose?

A

2

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18
Q

What is the net gain of ATP per glucose from glycolysis?

A

2

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19
Q

Where does glycolysis occur?

A

Cytosol

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20
Q

What enzyme converts glucose into glucose-6-phosphate?

A

Hexokinase (glucokinase in liver)

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21
Q

What is the difference between hexokinase and glucokinase?

A

Glucokinase is not inhibited by its product whereas hexokinase is

Glucokinase only present in liver

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22
Q

What is the key control enzyme of glycolysis?

A

Phosphofructokinase-1

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23
Q

What does phosphofructokinase-1 do?

A

Converts Fructose-6-P into Fructose 1,6 bisphosphate

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24
Q

What does pyruvate kinase do?

A

Converts phosphoenolypyruvate (PEP) into pyruvate

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25
Q

Why are there so many steps/enzymes involved in glycolysis?

A

Chemistry easier in small stages, allows for production of useful intermediates, allows for fine control

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26
Q

Why is glucose phosphorylated in the first step of glycolysis?

A

Makes glucose negatively charged, prevents passage back across plasma membrane, increases reactivity

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27
Q

How many moles of ATP are used per mole of glucose in the investment phase?

A

2

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28
Q

What are steps 1, 2 and 3 of the investment phase of glycolysis?

A

Glucose -> Glucose-6-P
Glucose-6-P -> Frutose-6-P
Fructose-6-P -> Fructose 1,6-bis-P

1) and 3) are irreversible as they have large negative /\G

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29
Q

What is the committing step of glycolysis?

A

Fructose-6-P -> Fructose 1,6-bis-P

Commits glucose to metabolism via glycolysis

30
Q

What happens in reaction 4 of glycolysis?

A

Cleavage of C6 ainto 2 C3 units

Fructose 1,6-bis-P into Glyceraldehyde 3-P and DHAP

31
Q

What happens in reaction 6 of glycolysis?

A

Glyceraldehyde-3-P into 1,3-bis phosphoglycerate

NAD reduced to NADH

32
Q

What happens in reactions 7 and 10 of glycolysis?

A

ATP synthesis

In reaction 7: 1,3-BPG and PEP transfer Pi to ADP to give ATP - substrate level phosphorylation

33
Q

Why is reaction 10 of glycolysis irreversible?

A

Large negative /\G

34
Q

How many irreversible steps are there in glycolysis?

A

3

35
Q

How many times greater is the rate of glycolysis in cancer?

A

x200

36
Q

What is the clinical application of glycolysis and cancer?

A

Measure uptake of FDG (radioactive modified hexokinase substrate)

Imaging with positron emission tomography
(PET scan)

37
Q

How is PFK allosterically regulated?

A

Inhibited by high ATP and stimulated by high AMP

38
Q

How is PFK hormonally regulated?

A

Stimulated by insulin, inhibited by glucagon (because glucagon stimulates gluconeogenesis so you don’t want to use glucose up in glycolysis)

39
Q

How is hexokinase inhibited?

A

Product inhibition by G6P

40
Q

Why is DHAP an important intermediate?

A

Converted to glycerol phosphate by glycerol 3 phosphate dehydrogenase

(Glycerol phosphate important to triglyceride and phospholipid biosynthesis)

41
Q

Why is 1,3-BPG an important intermediate?

A

Converted to 2,3 BPG by bisphosphoglycerate mutase

42
Q

What does glycerol 3-phosphate dehydrogenase do?

A

Catalyses the reversible redox reaction of DHAP to glycerol phosphate

43
Q

What does bisphosphoglycerate mutase do?

A

Catalyses the reversible reation of 1,3-BPG to 2,3-BPG

Unique to erythrocytes and placental cells

44
Q

How is NAD+ regenerated?

A

Usually from NADH in stage 4 of metabolism
or
Regenerated by lactate dehydrogenase

NADH + pyruvate + H+ —> lactate + NAD+

45
Q

What defines hyperlactaemia?

A

2-5 mM lactate - no change in blood pH due to buffering capacity

46
Q

What defines lactic acidosis?

A

Above 5 mM lactate - lowers blood pH

47
Q

What enzymes are involved in galatose metabolism?

A

Galactokinase, uridyl transferase and UDP-galactose epimerase

48
Q

Where is fructose metablised in humans?

A

Liver

49
Q

What is essential fructosuria?

A

Fructokinase missing

Fructose in urine, no clinical signs

50
Q

What is fructose intolerance?

A

Aldolase missing

Fructose-1-P accumulates in liver leading to liver damage

51
Q

Where does the pentose phosphate pathway occur?

A

Cytosol

52
Q

What is ribose-5-P required for?

A

Nucleotides, DNA, RNA, coenzymes

53
Q

What is NADPH required for?

A

Fatty acid biosynthesis, steroid biosynthesis, GSH regeneration

54
Q

Is ATP synthesised or CO2 produced in the pentose phosphate pathway?

A

No ATP synthesised but CO2 produced

55
Q

What is the rate limiting enzyme in the pentose phosphate pathway?

A

Glucose 6-phosphate dehydrogenase

56
Q

What can cause galactosaemia?

A

Deficiency in galactokinase, uridyl transferase or UDP-galactose epimerase

57
Q

What does galactokinase do?

A

Converts galactose into galactose-1-P

58
Q

What does uridyl transferase do?

A

Converts galactose-1-P into Glucose-1-P

59
Q

What does UDP-galactose epimerase do?

A

Converts galactose-1-P into UDP-galactose

60
Q

How is galactose metabolised?

A

Galactose –> Galactose 1 P

Galactose 1 P –> UDP Galactose –> UDP glucose –> Glycogen

OR

Galactose 1 P –> Glucose 1 P –> Glucose 6 P –> Glycolysis

61
Q

What does fructokinase do?

A

Converts fructose into fructose 1 P

62
Q

What does aldolase do?

A

Converts fructose 1 P into Glyceraldehyde and DHAP

63
Q

In fructose metabolism, what happens to glyceraldehyde and DHAP?

A

Form glyceraldehyde-3-P which enters glycolysis

catalysed by triokinase and TPI

64
Q

What does the pentose phosphate pathway start from?

A

Glucose-6-Phosphate

65
Q

What are the 2 important things produced from the pentose phosphate pathway?

A

NADPH and Ribose-5-phosphate

66
Q

What accumulates in tissues in the absence of the galactokinase enzyme?

A

Galactose

67
Q

What accumulates in tissues in the absence of the uridyl transferase enzyme?

A

Galactose and galactose-1-P

68
Q

What does accumulation of galactose in tissues lead to?

A

Its reduction to galactitol by aldose reductase

69
Q

Why does depletion of NADPH lead to compromised defences against oxidative damage?

A

Glutathione reductase uses NADPH as electron donor and NADPH is a structural component of catalase

70
Q

Why does galactosaemia cause cataracts?

A

Increased galactose levels -> aldose reductase
Aldose reductase catalyses the conversion of galactose to galacitol - build up increases osmotic pressure draws water into lens

ESA2 - Metabolism, Endocrinology and Haematology (19 decks)

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