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Metabolism > Session 2 > Flashcards

Session 2 Flashcards

0
Q

What are the features of carbohydrates?

A
  • hydrophilic as have many OH groups

- partially oxidised (need less oxygen than fatty acids for complete oxidation)

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1
Q

What is the general structure of carbohydrates and how are they categorised?

A
  • (CH2O)n
  • are either aldose (with an aldehyde group) or ketose (with a ketone group) sugars
  • Exist as monosaccharide (triose, pentose or hexose), disaccharides (eg maltose (glu/glu), lactose (galac/glu), sucrose (fructose/glu), oligosaccarides or polysaccharides (glycogen, starch or cellulose)
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2
Q

Where is glycogen stored?

A
  • Liver

- Skeletal muscle

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3
Q

What bonds are in glycogen?

A
  • a-1,4-glycosidic bonds and a-1,6-glycosidic bonds (branches)
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4
Q

What makes up starch and what bonds are there?

A
  • amylose (a-1,4-glycosidic bonds)

- amylopectin (a-1,4 and a-1,6-glycosidic bonds)

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5
Q

Why can’t humans digest cellulose?

A
  • humans do not have the enzyme required to break B-1,4-glycosidic bonds
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6
Q

What enzymes are involved in metabolising dietary carbohydrates so they can be absorbed?

A
  • amylase (in the saliva and pancreas)

- small intestine: lactase, sucrase, glycoamylase, isomaltase

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7
Q

What are the main functions of glycolysis?

A
  • Oxidises glucose

- Produces NADH, ATP and C3 and C6 intermediates

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8
Q

What are the main features of glycolysis?

A
  • Exergonic
  • Oxidative
  • Can operate anaerobic ally
  • Irreversible
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9
Q

What is the overall reaction for glucose?

A

Glucose + 2Pi + 2ADP + 2NAD+ ->

2pyruvate + 2ATP + 2NADH + 2H+ + 2H2O

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10
Q

What are the important steps in glycolysis is and what are their enzymes?

A
  • 1: glucose -> glucose 6-phosphate (hexokinase (glucokinase in liver))
  • 3: fructose 6-phosphate -> fructose 1,6-bus phosphate (phosphofructokinase)
  • 10: phosphoenolpyruvate -> pyruvate (pyruvate kinase)
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11
Q

Which steps in glycolysis are irreversible and why?

A
  • 1, 3 and 10

- have large negative

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12
Q

At which steps in glycolysis does substrate level phosphorylation occur?

A
  • 7 and 10
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13
Q

Which is the committing step in glycolysis?

A
  • 3
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14
Q

Which steps require an input of ATP in glycolysis?

A
  • 1 and 3
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15
Q

In which step of glycolysis is a C6 intermediate cleaved into 2 C3 intermediates?

A
  • 4
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16
Q

In which stage of glycolysis is NADH produced?

A
  • 6
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17
Q

What intermediate of glycolysis can be converted into glycerol phosphate? And what enzyme is used?

A
  • dihydroxyacetone phosphate -> glycerol phosphate
  • glycerol 3-phosphate dehydrogenase
    Dihydroxyacetone is the product of reaction 4
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18
Q

What is glycerol phosphate used for?

A
  • Used in triglyceride and phospholipid synthesis
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19
Q

Where is glycerol phosphate synthesised?

A
  • Adipose tissue

- Liver

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20
Q

What intermediate of glycolysis can be converted to 2,3-bisphosphoglycerate? What enzyme is used?

A
  • 1,3-bisphosphoglycerate -> 2,3-bisphosphoglycerate
  • Bisphosphoglycerate mutate
    1,3-Bisphosphoglycerate is the product of reaction 6
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21
Q

Where is 2,3-Bisphosphoglycerate synthesised?

A
  • Red blood cells
22
Q

How does NADH regulate glycolysis?

A
  • High NADH concentrations is a high energy level signal

- causes step 6, and therefore glycolysis, to be inhibited

23
Q

How can enzymes be regulated?

A
  • Allosterically (activator/inhibitor binds at a site that isn’t the active site)
  • Covalent modification (phosphorylation/dephosphorylation)
24
Q

How is glycolysis Allosterically regulated?

A
  • Reaction 1 Hexokinase: inhibited by glucose 6-phosphate (product inhibition)
  • Reaction 3 phosphofructokinase : in muscle - inhibited by high ATP:AMP ratio; in liver - activated by high insulin:glucagon ratio
  • Reaction 10 Pyruvate kinase: activated by high insulin:glucagon ratio
25
Q

What would happen to glycolysis if NAD+ is not regenerated?

A
  • NADH levels would be low and glycolysis would stop because step 6 is inhibited
26
Q

When is NAD+ regenerated in glycolysis?

A
  • Stage 4 of metabolism (oxidative phosphorylation/electron transport chain)
27
Q

Which stages of metabolism do not occur in red blood cells?

A
  • Stage 3 or 4

- Use anaerobic respiration instead to regenerated NAD+

28
Q

What is the lactate dehydrogenase reaction?

A
  • NADH + H+ + pyruvate NAD+ + lactate

- lactate dehydrogenase enzyme

29
Q

Where is lactate produced and where is it metabolised?

A
  • Produced by red blood cells and skeletal muscle

- Removed by liver and heart

30
Q

What happens to lactate in the heart?

A
  • converted to CO2
31
Q

What happens to lactate in the liver?

A
  • Converted to glucose in gluconeogenesis
32
Q

What is hyperlactaemia?

A
  • lactate is between 2-5 mM in the blood plasma
  • Below renal threshold
  • no change in blood pH
33
Q

What is lactate acidosis?

A
  • lactate is above 5mM in the blood plasma
  • Above renal threshold
  • Blood pH is lowered
34
Q

How is fructose metabolised?

A
  • Fructose -> fructose 1-phosphate
    ATP -> ADP (Fructokinase)
  • Fructose 1-phosphate -> glyceraldehyde 3-phosphate (aldolase)
    Glyceraldehyde 3-phosphate enters glycolysis at the beginning of step 6
    Takes place in liver
35
Q

What happens if fructokinase enzyme is missing?

A
  • Essential fructosuria: fructose in urine as exceeds renal threshold, no clinical signs
36
Q

What happens if Aldolase enzyme is missing?

A
  • Fructose intolerance: fructose 1-phosphate accumulates in liver causing liver damage; treat by removing fructose from diet
37
Q

Where is galactose metabolised?

A
  • Mainly in liver

- Also in kidney and gastrointestinal tract

38
Q

What is the overall reaction of galactose metabolism?

A
  • Galactose + ATP -> Glucose 6-phosphate + ADP
39
Q

How is galactose metabolised?

A
  • galactose -> galactose 1-phosphate
    ATP -> ADP (Galactokinase)
  • galactose 1-phosphate -> glucose 1-phosphate (galactose 1-Phosphate uridyl transferase)
    UDP-glucose -> UDP-galactose (UDP-galactose epimerase)
  • glucose 1-phosphate -> glucose 6-phosphate (enters glycolysis at beginning of step 2)
40
Q

What is galactosaemia?

A
  • Inability to utilise Glucose
41
Q

What types of galactosaemia are there?

A
  • Galactokinase deficiency (rare): galactose accumulates

- Transferase deficiency (common): galactose and galactose 1-phosphate accumulates

42
Q

What happens with an accumulation of galactose?

A
  • Galactose enters other pathways
  • Galactose -> galactitol (aldose reductase)
    NADPH -> NADP+
  • Depletes NADPH - causes cataracts in eyes as lens structure is damaged
  • High galactose concentration causes non-enzymatic glycosylation of the lens proteins -> contributes to cataract formation
  • Accumulation of galactose and galactitol -> raised intra-ocular pressure (glaucoma) -> blindness
43
Q

What happens with an accumulation of galactose 1-phosphate?

A
  • Damage to liver, kidney and brain
44
Q

How is galactosaemia treated?

A
  • No lactose in diet
45
Q

How does the depletion of NADPH cause cataracts?

A
  • NADPH normally prevents disulphide bonds forming by reducing disulphide bonds
  • -S-S- -> -SH HS-
    NADPH -> NADP+
  • In galactosaemia there is not enough to do so when also converting galactose to galactitol (by reduction) as NADPH is oxidised and cannot reduce the disulphide bonds any longer
  • This damages the structure of proteins that contain free -SH groups (sulphydryl groups)
46
Q

Where does the pentose phosphate pathway occur?

A
  • Liver
  • Red blood cells
  • Adipose tissue
47
Q

What are the key features of the pentose phosphate pathway?

A
  • 2 stage process:
    ~ oxidative decarboxylation
    ~ rearrangement to glycolysis intermediates
  • Takes place in the cytoplasm
  • No ATP production
  • Loss of CO2 (therefore is irreversible)
  • Glucose 6-phosphate dehydrogenase is controlled by NADP+/NADPH ratio (inhibited by NADPH and activated by NADP+)
48
Q

What happens in the stages of the pentose phosphate pathway?

A
  • Oxidative decarboxylation:
    Glucose 6-phosphate -> C5 sugar phosphate + CO2
    NADP+ -> NADPH
    Enzymes: glucose 6-phosphate dehydrogenase
    6-phosphogluconate dehydrogenase
  • Rearrangement to glycolytic intermediates:
    3 C5 sugars —–> 2 fructose 6-phosphate +
    1 glyceraldehyde 3-phosphate
49
Q

What are the functions of pentose phosphate pathway?

A
  • Produce NADPH in cytoplasm for:
    ~ Biosynthetic reducing power eg lipid synthesis (therefore high
    activity in liver and adipose tissue)
    ~ Maintain free -SH (cysteine) groups on certain proteins (prevents
    oxidation to -S-S- disulphide bonds)
  • Produce C5 sugars for nucleotides needed for nucleic acid synthesis (therefore high activity in dividing tissues eg bone marrow)
50
Q

What happens with a glucose 6-phosphate dehydrogenase deficiency?

A
  • Pentose phosphate pathway does not occur
  • Very common inherited defect
  • Reduces amount of NADPH produced
  • Therefore disulphide bonds cannot be reduced back in free cysteine groups (-SH)
51
Q

What does the lack of NADPH in glucose 6-phosphate deficiency cause?

A
  • In red blood cells: ⬇️ NADPH -> disulphide bonds formed -> proteins aggregate -> Heinz bodies form -> ⬆️ haemolysis
  • Acute haemolytic episodes are precipitated by chemicals that reduce NADPH levels (eg antimalarials, sulphonamides, certain glycosides found in broad beans)
  • In lens of eye: ⬇️ NADPH -> disulphide bonds form -> cataracts
52
Q

What causes a glucose 6-phosphate dehydrogenase deficiency?

A
  • X-linked gene defect found in some populations eg Mediterranean region and black USA males
  • Point mutation in the gene coding for glucose 6-phosphate dehydrogenase
  • Results in reduced activity of enzyme
53
Q

What is the function of glutathione?

A
  • Normally reduces NADP+ back to NADPH

- Becomes saturated when there is a lack of NADPH production

Metabolism (11 decks)

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