Session 2 Flashcards
(54 cards)
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)
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)
2
Q
Where is glycogen stored?
A
- Liver
- Skeletal muscle
3
Q
What bonds are in glycogen?
A
- a-1,4-glycosidic bonds and a-1,6-glycosidic bonds (branches)
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)
5
Q
Why can’t humans digest cellulose?
A
- humans do not have the enzyme required to break B-1,4-glycosidic bonds
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
7
Q
What are the main functions of glycolysis?
A
- Oxidises glucose
- Produces NADH, ATP and C3 and C6 intermediates
8
Q
What are the main features of glycolysis?
A
- Exergonic
- Oxidative
- Can operate anaerobic ally
- Irreversible
9
Q
What is the overall reaction for glucose?
A
Glucose + 2Pi + 2ADP + 2NAD+ ->
2pyruvate + 2ATP + 2NADH + 2H+ + 2H2O
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)
11
Q
Which steps in glycolysis are irreversible and why?
A
- 1, 3 and 10
- have large negative
12
Q
At which steps in glycolysis does substrate level phosphorylation occur?
A
- 7 and 10
13
Q
Which is the committing step in glycolysis?
A
- 3
14
Q
Which steps require an input of ATP in glycolysis?
A
- 1 and 3
15
Q
In which step of glycolysis is a C6 intermediate cleaved into 2 C3 intermediates?
A
- 4
16
Q
In which stage of glycolysis is NADH produced?
A
- 6
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
18
Q
What is glycerol phosphate used for?
A
- Used in triglyceride and phospholipid synthesis
19
Q
Where is glycerol phosphate synthesised?
A
- Adipose tissue
- Liver
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
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
How is glycolysis Allosterically regulated?
- 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
What would happen to glycolysis if NAD+ is not regenerated?
- NADH levels would be low and glycolysis would stop because step 6 is inhibited
26
When is NAD+ regenerated in glycolysis?
- Stage 4 of metabolism (oxidative phosphorylation/electron transport chain)
27
Which stages of metabolism do not occur in red blood cells?
- Stage 3 or 4
| - Use anaerobic respiration instead to regenerated NAD+
28
What is the lactate dehydrogenase reaction?
- NADH + H+ + pyruvate NAD+ + lactate
| - lactate dehydrogenase enzyme
29
Where is lactate produced and where is it metabolised?
- Produced by red blood cells and skeletal muscle
| - Removed by liver and heart
30
What happens to lactate in the heart?
- converted to CO2
31
What happens to lactate in the liver?
- Converted to glucose in gluconeogenesis
32
What is hyperlactaemia?
- lactate is between 2-5 mM in the blood plasma
- Below renal threshold
- no change in blood pH
33
What is lactate acidosis?
- lactate is above 5mM in the blood plasma
- Above renal threshold
- Blood pH is lowered
34
How is fructose metabolised?
- 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
What happens if fructokinase enzyme is missing?
- Essential fructosuria: fructose in urine as exceeds renal threshold, no clinical signs
36
What happens if Aldolase enzyme is missing?
- Fructose intolerance: fructose 1-phosphate accumulates in liver causing liver damage; treat by removing fructose from diet
37
Where is galactose metabolised?
- Mainly in liver
| - Also in kidney and gastrointestinal tract
38
What is the overall reaction of galactose metabolism?
- Galactose + ATP -> Glucose 6-phosphate + ADP
39
How is galactose metabolised?
- 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
What is galactosaemia?
- Inability to utilise Glucose
41
What types of galactosaemia are there?
- Galactokinase deficiency (rare): galactose accumulates
| - Transferase deficiency (common): galactose and galactose 1-phosphate accumulates
42
What happens with an accumulation of galactose?
- 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
What happens with an accumulation of galactose 1-phosphate?
- Damage to liver, kidney and brain
44
How is galactosaemia treated?
- No lactose in diet
45
How does the depletion of NADPH cause cataracts?
- 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
Where does the pentose phosphate pathway occur?
- Liver
- Red blood cells
- Adipose tissue
47
What are the key features of the pentose phosphate pathway?
- 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
What happens in the stages of the pentose phosphate pathway?
- 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
What are the functions of pentose phosphate pathway?
- 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
What happens with a glucose 6-phosphate dehydrogenase deficiency?
- 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
What does the lack of NADPH in glucose 6-phosphate deficiency cause?
- 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
What causes a glucose 6-phosphate dehydrogenase deficiency?
- 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
What is the function of glutathione?
- Normally reduces NADP+ back to NADPH
| - Becomes saturated when there is a lack of NADPH production
