Session 2 Flashcards
What are the features of carbohydrates?
- hydrophilic as have many OH groups
- partially oxidised (need less oxygen than fatty acids for complete oxidation)
What is the general structure of carbohydrates and how are they categorised?
- (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)
Where is glycogen stored?
- Liver
- Skeletal muscle
What bonds are in glycogen?
- a-1,4-glycosidic bonds and a-1,6-glycosidic bonds (branches)
What makes up starch and what bonds are there?
- amylose (a-1,4-glycosidic bonds)
- amylopectin (a-1,4 and a-1,6-glycosidic bonds)
Why can’t humans digest cellulose?
- humans do not have the enzyme required to break B-1,4-glycosidic bonds
What enzymes are involved in metabolising dietary carbohydrates so they can be absorbed?
- amylase (in the saliva and pancreas)
- small intestine: lactase, sucrase, glycoamylase, isomaltase
What are the main functions of glycolysis?
- Oxidises glucose
- Produces NADH, ATP and C3 and C6 intermediates
What are the main features of glycolysis?
- Exergonic
- Oxidative
- Can operate anaerobic ally
- Irreversible
What is the overall reaction for glucose?
Glucose + 2Pi + 2ADP + 2NAD+ ->
2pyruvate + 2ATP + 2NADH + 2H+ + 2H2O
What are the important steps in glycolysis is and what are their enzymes?
- 1: glucose -> glucose 6-phosphate (hexokinase (glucokinase in liver))
- 3: fructose 6-phosphate -> fructose 1,6-bus phosphate (phosphofructokinase)
- 10: phosphoenolpyruvate -> pyruvate (pyruvate kinase)
Which steps in glycolysis are irreversible and why?
- 1, 3 and 10
- have large negative
At which steps in glycolysis does substrate level phosphorylation occur?
- 7 and 10
Which is the committing step in glycolysis?
- 3
Which steps require an input of ATP in glycolysis?
- 1 and 3
In which step of glycolysis is a C6 intermediate cleaved into 2 C3 intermediates?
- 4
In which stage of glycolysis is NADH produced?
- 6
What intermediate of glycolysis can be converted into glycerol phosphate? And what enzyme is used?
- dihydroxyacetone phosphate -> glycerol phosphate
- glycerol 3-phosphate dehydrogenase
Dihydroxyacetone is the product of reaction 4
What is glycerol phosphate used for?
- Used in triglyceride and phospholipid synthesis
Where is glycerol phosphate synthesised?
- Adipose tissue
- Liver
What intermediate of glycolysis can be converted to 2,3-bisphosphoglycerate? What enzyme is used?
- 1,3-bisphosphoglycerate -> 2,3-bisphosphoglycerate
- Bisphosphoglycerate mutate
1,3-Bisphosphoglycerate is the product of reaction 6
Where is 2,3-Bisphosphoglycerate synthesised?
- Red blood cells
How does NADH regulate glycolysis?
- High NADH concentrations is a high energy level signal
- causes step 6, and therefore glycolysis, to be inhibited
How can enzymes be regulated?
- Allosterically (activator/inhibitor binds at a site that isn’t the active site)
- Covalent modification (phosphorylation/dephosphorylation)
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
What would happen to glycolysis if NAD+ is not regenerated?
- NADH levels would be low and glycolysis would stop because step 6 is inhibited
When is NAD+ regenerated in glycolysis?
- Stage 4 of metabolism (oxidative phosphorylation/electron transport chain)
Which stages of metabolism do not occur in red blood cells?
- Stage 3 or 4
- Use anaerobic respiration instead to regenerated NAD+
What is the lactate dehydrogenase reaction?
- NADH + H+ + pyruvate NAD+ + lactate
- lactate dehydrogenase enzyme
Where is lactate produced and where is it metabolised?
- Produced by red blood cells and skeletal muscle
- Removed by liver and heart
What happens to lactate in the heart?
- converted to CO2
What happens to lactate in the liver?
- Converted to glucose in gluconeogenesis
What is hyperlactaemia?
- lactate is between 2-5 mM in the blood plasma
- Below renal threshold
- no change in blood pH
What is lactate acidosis?
- lactate is above 5mM in the blood plasma
- Above renal threshold
- Blood pH is lowered
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
What happens if fructokinase enzyme is missing?
- Essential fructosuria: fructose in urine as exceeds renal threshold, no clinical signs
What happens if Aldolase enzyme is missing?
- Fructose intolerance: fructose 1-phosphate accumulates in liver causing liver damage; treat by removing fructose from diet
Where is galactose metabolised?
- Mainly in liver
- Also in kidney and gastrointestinal tract
What is the overall reaction of galactose metabolism?
- Galactose + ATP -> Glucose 6-phosphate + ADP
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)
What is galactosaemia?
- Inability to utilise Glucose
What types of galactosaemia are there?
- Galactokinase deficiency (rare): galactose accumulates
- Transferase deficiency (common): galactose and galactose 1-phosphate accumulates
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
What happens with an accumulation of galactose 1-phosphate?
- Damage to liver, kidney and brain
How is galactosaemia treated?
- No lactose in diet
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)
Where does the pentose phosphate pathway occur?
- Liver
- Red blood cells
- Adipose tissue
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+)
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
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)
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)
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
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
What is the function of glutathione?
- Normally reduces NADP+ back to NADPH
- Becomes saturated when there is a lack of NADPH production
