Carbs 2 Flashcards
Why does glycolysis need to be regulated
- control flux in response to demand
What is the most important regulatory enzyme in glycolysis
phosphofructokinase - 1
What are the two ways phosphofructokinase-1 can be regulated
allosteric
hormonal
What molecules allosterically inhibit phosphofructokinase-1
high ATP
high citrate
What molecules allosterically stimulate phosphofructokinase-1
high AMP
high fructose-2,6-bisphosphate
What are high energy signals
indicate cell has enough energy
ATP
NADH
FADH2
NADPH
What are low energy signals
indicate the cell is using and requires energy
AMP/ADP
NAD
FAD
NADP
What are two other regulatory enzymes in glycolysis
hexokinase (not glucokinase in liver)
pyruvate kinase
how is hexokinase regulated in glycolysis
end product inhibition
G6P
how is pyruvate kinase regulated
hormonal
high insulin : low glucagon
Why is lactate produced
- step 6 of glycolysis needs constant NAD source
- done when insufficient oxygen
- done in cells with no mitochondria e.g. RBC
What enzyme produces lactate
lactate dehydrogenase
What is the equation for pyruvate to lactate
2 pyruvate + 2 NADH + 2H+ –> 2 lactate + 2NAD+
How is lactate used
- by heart to turn back to pyruvate for energy
- by liver and kidney for pyruvate for energy or gluconeogenesis
What are normal plasma levels of lactate
less than 1 nm
What lactate levels suggest hyperlactaemia
2-5 nm
What plasma lactic levels suggest lactic acidosis
above 5nm
what is the normal production of lactate in a day without exercise
40-50 g
What can strenuous exercise increase plasma lactate levels by a min
10g
what is galactose require for
synthesis of glycolipids and glycoproteins
Where is galactose found in diet
lactose
Where is galactose metabolised
liver
What enzyme is used in the first reaction of glycolysis
galactokinase
What is the reaction of galactokinase
galactose + ATP –> galactose-1-p + ADP + Pi
What is the second enzyme in galactose metabolism
galactose-1-p uridyl transferase
What does the enzyme galactose-1-p uridyl transferase do
transfers a UDP group from UDP-glucose to galactose-1-p to make glucose-1-p (which enters glycolysis) and UDP galactose
How is UDP glucose regenerate and with what enzyme
UDP-galactose-4-epimerase converts UDP-galactose to UDP-glucose by changing orientation of OH group
Why is the UDP-galactose-4-epimerase enzyme important for pregnancy
allows production of lactose from glucose via UDP- glucose
Where does fructose come from in the diet
sucrose
where is fructose metabolised
liver
What is the first enzymes required in fructose metabolism
fructokinase
What is the reaction for fructokinase
fructose + ATP –> fructose-1-p + ADP + Pi
What is the second enzyme in fructose metabolism
adolase
What is the reaction for adolase
fructose-1-p cleaved into glyceraldehyde and DHAP
What enzyme converts glyceraldehyde into glyceraldehyde-3-p
triose kinase
requires ATP
What enzyme converts DHAP into glyceraldehyde-3-p
TPI
What are the two conditions involving fructose
- essential fructosuria
- fructose intolerance
What is essential fructosuria
fructokinase missing
fructose in urine
What enzyme is missing in fructose intolerance
adolase
what is the result of fructose intolerance
fructose-1-p accumulates in liver
cells depleted of Pi
liver damage
how is fructose intolerance managed
remove all fructose and sucrose from diet
What is galactosemia
unable to digest galactose
What are the two causes of galactosemia
- galactokinase deficiency
- transferase deficiency (most damage)
- epimerase deficiency
What are the symptoms of galactosemia
- hepatomegaly and cirrhosis
- renal failure
- vomiting
- seizure and brain damage
- cataract
- hypoglycemia
What happens when galactose accumulates
reduced to galacticol
What enzyme converts galactose to galacticol
aldose reductase
What does aldose reductase require to reduce galactose to galacticol
NADPH
Why does a lack of GALT enzyme cause a lot of damage
accumulation of galactose-1-p causes liver, kidney and brain damage and depletes cells of Pi
Explain how galactosemia can cause cataracts
- build up of galactose converted to galacticol by aldose reductase
- this uses up excessive NADPH
- compromises defences against oxidative damage
- ox damage causes cross linkages of S-S disulphide bonds in lens causing crystallisation
How does galactosemia relate to glaucoma
accumulation of galactose and galacticol in lens increases intra-ocular pressure
What is the treatment for galactosemia
remove lactose from diet
What are the defences against oxidative damage
- glutathione ( uses NADPH for electron donor)
- catalase (NADPH structural component)
- thioredoxin system (NADPH electron donor)
- thiltransferase system (uses glutathione as cofactor)
How can galactose still be produced on galactose free diet for lactation
using glucose and UDP galactose which can be made from UDP glucose to make lactose through lactose synthase
What is the importance of the pentose phosphate pathway
- major source of NADPH
- generates pentose sugars for nucleotides
What is the starting point for pentose phosphate pathway
some of glucose-6-phosphate from glycolysis
What is the first enzyme in the pentose phosphate pathway
glucose-6-p dehydrogenase
What is the reaction for the enzyme glucose-6-p dehydrogenase
glucose-6-p + NADP –> 6-phosphogluconolacetone + NADPH
What happens to any unused 5C sugars from pentose phosphate pathway
converts any unused sugars 5C sugars to intermediates of glycolysis
What is the regulatory enzyme in the pentose phosphate pathway
glucose-6-p dehydrogenase
How is the enzyme glucose-6-p dehydrogenase regulated
NADP : NADPH ratio.
NADPH inhibiting
NADP activating
Where is the glucose-6-p dehydrogenase enzyme found
X chromosome
What does a deficiency in glucose-6-p dehydrogenase cause
low NADPH
less glutathione
this causes less protection from oxidative damage
Why is NADPH require for glutathione synthesis
NADPH require to reduce oxidised form of glutathione back to active reduced form
Why are RBC particularly affected by glucose-6-p dehydrogenase deficiency
pentose phosphate pathway is RBC only source of NADPH
- Hb cross linked by disulphide bonds from ox damage
- forms insoluble aggregates called Heinz bodies
- haemolysis
