Fermentation and Regulation of Glycolysis Flashcards
Glycolysis sucks at producing ATP, but is necessary bc it produces
2NADH which is necessary further down to produce ATP
Regeneration of NAD+
There are limited amounts of NAD+ in the cell which is derived from vitamin niacin
NAD+ must be regenerated for glycolysis to proceed
The 3 possible fates for pyruvate:
1) Anaerobic conditions for plants = alcoholic fermentation
2) Anaerobic conditions for humans = lactic acid fermentation
3) Aerobic conditions = CAC
Alcoholic fermentation
Releases CO2 going to acetaldehyde, then releases NAD+ and produces ethanol
Lactic acid fermentation
Releases NAD+ and produces lactate
Aerobic conditions for pyruvate
Produces Acetyl CoA, which releases a CO2
then proceeds for further oxidation
Pyruvate from the cytosol then enters the
mitochondria to produce Acetyl CoA
What steps/enzymes of glycolysis are regulated and irreversible?
- Hexokinase (step 1)
- PFK-1 (step 3)
- Pyruvate kinase (step 10)
All of these points are where ATP is used/produced in irreversible rxns
These regulatory enzymes become more or less active in response to the reversible binding of
allosteric effectors or covalent modification (Pi addition or removal)
Which step of glycolysis is the most regulated, also known as the pacemaker of glycolysis?
PFK-1 (step 3)
Glycolysis in the skeletal muscles provide
ATP to power contraction (movement)
High ATP/low AMP = glycolysis inhibited bc already have energy
High AMP/low ATP = glycolysis stimulated bc need energy
Phosphofructokinase is the most important control site because:
High levels of ATP allosterically inhibit the enzyme -> lowers its affinity for f-6-p
AMP reverses the inhibitory action of ATP (binds to enzyme = change in conformation) -> AMP competes with ATP for binding site, but when bound, does not inhibit the enzyme
PFK-1 is also inhibited by a decrease in
pH. The inhibition of glycolysis, and therefore lactic acid fermentation, protects the muscle from damage that would result from the accumulation of too much acid
Why does AMP but no ADP stimulate the activity of PFK-1?
Because ADP is used to make ATP, AMP is produced as a result
Hexokinase is inhibited by its product:
g-6-p and when PFK-1 is inhibited then f-6-p increases and g-6-p is favoured, leading to the inhibition of hexokinase
What inhibits pyruvate kinase?
ATP allosterically inhibits pyruvate kinase to decrease rate of glycolysis when the energy charge of the cell is high
If glycolysis increases, f-1,6-bp activates the pyruvate kinase
The liver maintains blood-glucose concentration:
stores glucose as glycogen when glucose is plentiful, and it releases glucose when supplies are low
Also uses glucose to generate reducing power (NADPH) for biosynthesis and to synthesize building blocks for other biomolecules
In the liver, glycolysis is inhibited by:
Citrate, which means that biosynthetic precursors are abundant, there is no need to degrade additional glucose for this purpose
F-1,6-BP in the liver stimulates glycolysis:
- increasing PFK-1’s affinity for F-6-p
- Diminishing the inhibitory effect of ATP
= Feedforward stimulation
Glucokinase in the liver
Only phosphorylates glucose when glucose is abundant
Km for glucose is ~50x more than hexokinase
It is not inhibited by g-6-p (its product)
When there is low glucose concentration, glucokinase is
inhibited by the liver specific glucokinase regulatory protein (GKRP) - sequesters kinase in the nucleus
Glucokinase is also present in the pancreas:
Increased formation of g-6-p when blood-glucose levels are elevated secretion of insulin signals the need to remove glucose from blood for storage as glycogen or conversion into fat
Pyruvate kinase in the liver
Low blood-glucose concentration -> glucagon-trigger cyclic AMP cascade -> phosphorylation of pyruvate kinase
High blood-glucose -> dephospho pyruvate kinase more active
ATP inhibits pyruvate kinase
GLUT2 is located where?
Liver and pancreatic B cells
regulation of insulin and removes excess glucose from blood
GLUT4 is located where?
Muscle and fat cells
