Glycolysis Flashcards
What are the two enzymes that convert glucose to glucose-6-phosphate?
- Hexokinase
- Glucokinase
What does Hexokinase do?
- high affinity (low KM) but low capacity (low VM)
- found in most tissues
- inhibited by glucose-6-phosphate/not induced by insulin
What does glucokinase do?
- low affinity (high KM) but high capacity (high VM)
- found in the liver and β-cells
- NOT inhibited by glucose-6-phosphate/induced by insulin
Describe production of 2,3BPG
- Bypass of 1,3BPG to 3PG, step makes 2ATP
- side reaction of glycolysis
- important in RBC (binding or 2,3BPG stabilizes the deoxy form, facilitates release delivery of oxygen to the tissues)
- reduces net production of glycolysis by 1 ATP when made
What are the 3 irreversible steps of regulation for glycolysis?
- Glucose to Glucose-6-Phosphate (hexokinase/Glucokinase)
- Fructose-6-Phosphate to Fructose-1,6-Bisphosphate (PFK-1) (KEY REGULATORY)
- Phosphoenolpyruvate (PEP) to pyruvate (pyruvate kinase)
Describe regulation of Glucose to Glucose-6-Phosphate.
- uses 1 ATP (traps glucose in cells)
- hexokinase: INHIBITED by G6P
- glucokinase: INDUCED by Insulin
Describe regulation of Fructose-6-Phosphate to Fructose-1,6-Bisphosphate (PFK-1).
-uses 1 ATP
-AMP and F-2,6-P activates
-ATP and citrate (plenty of stuff around to make ATP) inhibit
-Fructose 2,6-bisphosphate is the most potent activator of PFK-1
-formed by PFK-2 from F6P (kinase) and can be converted back into F6P (phosphatase)
-In liver, kinase domain is active if dephosphorylated and inactive if phosphorylated
-when active F-2,6-P is formed and this activates PFK-1
**also controls when glycolysis or gluconeogenesis is happening because F-2,6-P is an inhibitor of fructose 1,6-bisphosphatase (an enzyme of gluconeogenesis)
Describe Phosphoenolpyruvate (PEP) to pyruvate (pyruvate kinase) regulation.
- makes 1 ATP (2 per glucose molecule in glycolysis)
- phosphorylation (cAMP dependent) and alanine (made through amino transferase into pyruvate) inhibits
- F-1,6-P activates (feedforward mechanism)
Describe the well-fed state and its impact on glycolysis.
↓glucagon
↑insulin causes an ↑ in fructose 2,6-bisphosphate
↑ rate of glycolysis
Describe impact of starvation on glycolysis.
↑glucagon
↓insulin causes a ↓ in fructose 2,6-bisphosphate
↓ rate of glycolysis and ↑ rate of gluconeogenesis
Describe cAMP regulation of glycolysis.
- G-protein coupled receptor gets bound by a hormone or neurotransmitter
- G-proteins interact with receptor and activate adenylyl cyclase (makes cAMP from ATP)
- stops when the hormone is no longer bound to receptor
- cAMP activates protein kinases (Protein Kinase A) which phosphorylates enzymes (can either activate or inhibit them)
- protein phosphatases dephosphorylate the proteins and cAMP gets hydrolyzed (so changes in protein aren’t permanent)
- Cholera toxin and Whooping cough affect these G proteins
Describe insulin in regards to glycolysis.
- opposes the cAMP cascade
has intrinsic kinase activity that activate protein phosphatases that activate the hydrolysis of cAMP
-Insulin decreases blood glucose level by promoting the rapid uptake, storage and use of glucose
-especially a factor in muscle, adipose tissue and the liver
Describe insulin and its impact in the liver during glycolysis.
- Liver: insulin inactivates Phosphorylase (causes liver glycogen to split into glucose) so it prevents the breakdown of glycogen; causes enhanced uptake of glucose from the blood by liver cells (inc activity of glucokinase)
- activates the enzymes that promote glycogen synthesis (glycogen synthase)
Describe insulin and its impact in muscles during glycolysis.
-Muscle: increases the rate of glucose transport into resting cells (GLUT 4), stored as glycogen
Describe insulin and its impact in adipose tissue during glycolysis.
-Adipose Tissue: Insulin promotes FA Synthesis in the liver (makes TG which enter lipoproteins and go to adipose tissue)