Session 1: Carbohydrates, glycolysis, pentose phosphate pathway Flashcards

1
Q

What are the four stages of catabolism?

A
  1. Breakdown to building block molecules
    • Breakdown to metabolic intermediates
      - release of ‘reducing power’
  2. Kreb’s cycle
    • Oxidative phosphorylation
      - conversion of ‘reducing power’ into energy currency, ATP
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2
Q

What happens in stage 1 of carbohydrate metabolism? (3)

A
  1. Salivary amylase - starch/glycogen -> dextrins (oligosaccharides)
    2A. Pancreatic amylase - monosaccharides
    2B. Small intestine - disaccharidases attached to brush border of epithelial cells (lactase, sucrase, pancreatic amylase, isomaltase)
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3
Q

How can lactose intolerance come about?

A
  1. Primary lactase deficiency - lactase allele not expressed in adulthood
  2. Secondary lactase deficiency - reversible injury to small intestine
  3. Congenital lactase deficiency - autosomal recessive
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4
Q

How do monosaccharides reach the bloodstream?

A

Active transport

  • SGLT1 (gut to intestinal epithelial cells)
  • GLUT2 from intestinal epithelial to blood)
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5
Q

How are monosaccharides taken up by cells from blood?

A

Facilitated diffusion - GLUT 1-5

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6
Q

Where is GLUT2 found? (4)

A
  1. Kidney
  2. Liver
  3. Pancreatic beta cells
  4. Small intestine
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7
Q

Where is GLUT4 found? What is characteristic of this transport protein?

A
  1. Adipose tissue
  2. Striated muscle
    It is insulin-regulated
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8
Q

What is the average blood glucose level?

A

~5 mM

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9
Q

Which cells have an absolute requirement for glucose and why?

A
  1. RBCs - no mitochondria
  2. Neutrophils - use mt for oxidative burst
  3. Innermost cells of kidney medulla
  4. Lens of the eye - poor oxygen supply
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10
Q

Describe the CNS’ (brain’s) dependency on glucose.

A

Prefers glucose but can use ketone bodies for some energy requirements in times.
Concentration should meet or exceed Km for transporter to move glucose across BBB

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11
Q

What is produced in glycolysis?

A

Each glucose molecule produces:

  • 2 pyruvates (3C intermediates)
  • 2 NADH
  • 2 ATP
  • 6C intermediates
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12
Q

Where does glycolysis take place?

A

Cytosol

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13
Q

What are the 3 main enzymes involved in glycolysis?

A
  1. Hexokinase (glucokinase in liver)
  2. phosphofructokinase-1
  3. Pyruvate kinase
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14
Q

What is the committing step in glycolysis?

A

Fructose-6-P to fructose 1,6-bis-P

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15
Q

What is the main regulator of glycolysis?

A

PFK

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16
Q

What regulates PFK in the muscle?

A

High ATP - inhibits

High AMP - stimulates

17
Q

What regulates PFK in the liver?

A

Insulin - stimulates

Glucagon - inhibits

18
Q

Name all the regulators of glycolysis

A
  1. Insulin and glucagon
  2. ATP and AMP
  3. high NADH therefore low NAD+ inhibits
  4. G6-P product inhibition of hexokinase
  5. Insulin:glucagon ratio stimulates pyruvate kinase
19
Q

What is the significance of fructose 1,6-bis phosphate being broken down to DHAP (and G3P)?

A

DHAP important to triglyceride and phospholipid biosynthesis - forms glycerol phosphate which forms the backbone of triacylglycerol
- produced in adipose and liver

20
Q

Which enzyme is involved in converting DHAP to glycerol phosphate?

A

Glycerol 3-phosphate dehydrogenase

21
Q

Which enzyme converts 1,3-bis phosphoglycerate to 2,3-bis phosphoglycerate?

A

Bisphosphoglycerate mutase

22
Q

What is the significance of 2,3-BPG?

A

Produced in RBCs to regulate affinity of Hb for O2 - BPG reduces affinity

23
Q

How is NAD+ regenerated in glucose metabolism? (2)

A
  1. Stage 4 - oxidative phosphorylation

2. Lactate dehydrogenase converts pyruvate to lactate and NAD+

24
Q

Which parts of the body have troubles with regeneration of NAD+ and why?

A
  • RBCs - no Kreb’s cycle or oxidative phosphorylation because no mitochondria
  • Gut and muscle - oxidative phosphorylation needs O2 and these organs get reduced O2 supply sometimes
25
Q

What happens to pyruvate in tissues with low O2 supply?

A

Lactate dehydrogenase reduces it to lactate using NADH, producing NAD+

26
Q

What happens to lactate once anaerobic respiration occurs in tissues?

A

Travels in blood to heart, liver and kidney

27
Q

What happens to lactate in the heart?

A
  • Lactate dehydrogenase oxidises lactate to pyruvate using NAD+, producing NADH
  • pyruvate is then oxidised to produce energy and CO2 (Kreb’s cycle)
28
Q

What happens to lactate in the liver and kidney?

A
  • lactate gets oxidised to pyruvate by lactate dehydrogenase

- pyruvate forms glucose through gluconeogenesis and is released back into blood

29
Q

How does fructose enter glycolysis?

A
  1. Fructose -> Fructose-1P (Fructose kinase)
  2. Fructose-1P -> Glyceraldehyde + DHAP (Aldolase)
  3. Glyceraldehyde -> G3P (Triose kinase)
  4. DHAP -> G3P (TPI)
  5. G3P x 2 enters glycolysis
30
Q

Which organ metabolises fructose?

A

Liver

31
Q

What is essential fructosuria?

Which enzyme is missing?

A

Fructose in urine - fructokinase missing

32
Q

Which enzyme is missing in patients with fructose intolerance? What happens as a result of this?

A

Aldolase is missing - fructose-1P accumulates in liver and leads to liver damage

33
Q

Which molecules does the pentose phosphate pathway start from?

A

Glucose-6P

34
Q

Which important molecules does the pentose phosphate pathway produce?

A

NADPH

Ribose-5P (ribose sugars)

35
Q

What is NADPH required for? (3)

A
  1. Reducing power for biosynthesis (fatty acids, steroids)
  2. Maintenance of glutathione levels
  3. Detoxification reactions
36
Q

What do C5 ribose sugars help synthesise?

A

Nucleotides

DNA and RNA

37
Q

What is the rate-Iimiting enzyme in the pentose phosphate pathway?

A

Glucose-6P dehydrogenase

38
Q

Where in the cell does the pentose phosphate pathway occur?

A

Cytosol