Carbohydrates and Glycolysis (2) Flashcards
Why is Dihydroxyacetone-P such an important intermediate in glycolysis? Where is it highly required?
DHAP is converted into Glycerol Phosphate by enzyme glycerol 3-P dehydrogenase. This reaction converts NAD+ to NADH.
Glycerol Phosphate converts into Fat (triacylglycerol) by combining with fatty acids.
So DHAP is important for producing necessary fats from glycolysis.
Produced in adipose tissue and liver
Liver can phosphorylate glycerol directly
Where is 1,3-bis phosphoglycerate located in glycolysis? Why is it an important intermediate?
Step 6 converts Glyceraldehyde 3-P into 1,3-bis phosphoglycerate.
Converted into 2,3-bis phosphoglycerate by bisphosphoglycerate mutase. This new product is produced in RBC and used to determine O2 carrying capacity for haemaglobin. More of this product makes it easier for haemaglobin to release O2.
2 moles of NADH are produced from NAD+ per mole of glucose. Therefore, NAD+ needs to be regenerated in the cell. Where/when does this occur? Implying this, what problems do RBCs face, and what do they do instead?
During stage 4 of metabolism, NAD+ is regenerated from NADH.
RBC have no stage 3 or 4 of metabolism (no Krebs Cycle or Oxidative Phosphorylation)
So instead they regenerate NAD+ by using Lactate Dehydrogenase reaction (LDH)
How much lactate is produced in the body under certain circumstances?
Without major exercise = 40-50g/24 hours
RBC, skin, brain, muscles etc.
With strenuous exercise (inc. a lot of eating) = 30g/5 min
Normalises after 90 min
What is the reaction for NADH to NAD+ by LDH?
NADH + H+ + Pyruvate <—–> NAD+ + Lactate
Lactate released into blood and metabolised by liver and heart (they convert NAD+ back into NADH)
Lactate is acidic, and causes stitches
How do tissues gain Lactate in low O2 conditions?
Pyruvate converts to Lactate instead of undergoing Oxidative Phosphorylation, which requires O2
How are plasma lactate concentrations determined by?
1) Production
2) Utilisation (liver, heart, muscle)
3) Disposal (kidney)
How does the plasma lactate conc. change with Hyerlactaemia?
2-5mM
Below renal threshold
No change in blood pH (buffering capacity)
How does the plasma lactate conc. change with Lactic Acidosis?
Above 5mM
Above renal threshold
Blood lowered pH
What is normal lactate conc. in plasma?
Below 1mM
What are 2 clinical diseases which affect Fructose metabolism?
Essential Fructosuria:
Fructokinase missing, so fructose in urine
Fructose Intolerance:
Aldolase missing, Fructose -1-P accumulates in liver causing liver damage
Nobodys sure why, so solution is dont eat fructose
How can drinking Lactose cause galactosaemia?
Lactose is disaccharide of Glucose and Glaactose
Galactose digestion enzymes can have deficiencies and cause galactosaemia
3 enzymes:
Galactokinase (rarely affected)
Uridyl Transferase (common)
UDP-galactose epimerase
Treatment: No Lactose
Function of Galactokinase.
Converts galactose into galactose 1-P
Function of Uridyl Transferase
Converts galactose 1-P into Glucose 1-P
Leads onto Glocse 6-P for glycolysis beginning
Function of UDP-galactose epimerase
Converts Galactose 1-P into UDP-galactose.
This in turn converts into UDP-glucse and then into glycogen!
What happens to galactose when someone has galactosaemia?
Galactose builds up and as a result it enters other pathways which are harmful for the body.
Eg. cataracts, Galactose 1-P affects liver, kidney, brain etc.
How does galactosaemia cause cataracts?
Galactose buildup leads to new reaction pathways and these deplete NADPH
NADPH loss results in loss of free sulphydryl groups on proteins as inappropriate disulphide bonds form.
This causes a loss of functional integrity of proteins on lens of eye, causing cataracts.
What is the pentose phosphate pathway?
From glycolysis, glucose 6-P is taken down a pathway to become Ribose-5-P and other 5C sugars (pentose).
By enzyme G6PDH
Requires NADH+ to become NADPH x2
NADPH is used for fatty acid and steroid biosynthesis
What are the pentose sugars needed for?
Nucelotides
DNA
RNA
Coenzymes
How do these 5C sugars feed back into the glycolysis reaction?
Ribulose 5-P is converted into 6C and 3C sugars which are used by glycolysis
This occurs via a series of non oxidative reactions.
The oxidative decarboxylation (first) reaction of the PPP produces a CO2 molecule. What does this tell you of the reaction?
The reaction is irreversible.
Functions of PPP?
1) Produces NADPH:
a) Has a biosynthetic reducing power for eg. lipid synthesis
b) Helps with maintaining free cysteine groups (-SH) so prevents cataracts
2) Produces C5 sugars for nucelotides so this occurs a lot in dividing tissue
What would happen with a G6PDH deficiency on the PPP?
Lack of PPP occurring so a lack of C5 sugars
Also lack of NADPH so therefore structurally affecting free SH cysteine groups
This will lead to more S-S bonds which are harmful to the body
Eg. cataracts, or in RBC, formation of aggregated proteins creating heinz bodies, leading to Haemolysis
What is the PPPs rate limiting enzyme?
Glucose 6-P Dehydrogenase (G6PDH)
