Glycolysis and Carbohydrates Flashcards
Why is the glycolysis pathway not in equilibrium (i.e. one sided) even if most reactions occur at equilibrium?
- we have a basal metabolic rate
- we consume energy all the time
- body is an open system (we lose energy all the time)
What is Gibbs Free Energy and what does ΔG and ΔG° indicate?
- Gibbs free energy is the indicator of spontaneity
- ΔG: is the true indication of the direction of a reaction
- ΔG°: indicates the nature of the reaction (theoretical)
How do we know when a reaction is endergonic, exergonic, reversible, and irreversible?
- ender: ΔG° is positive (requires energy)
- exer: ΔG° is negative (releases energy)
- rever: ΔG is zero or close to zero
- irrever: ΔG is much less that zero
How is glucose absorbed into the blood?
in the intestine:
- active transport: by Na+/glucose symport and Na+/K+ ATPase
- passive transport: glucose uniport
what pancreatic cell type uptakes glucose?
pancreatic B-cells
how/when does the pancreas uptake glucose and what is its role?
glucose goes in cells through Glut2 when [glucose] > 5.5mM and it releases insulin:
- no glucose: K(ATP) channel pumps K+ out, causing membrane hyper-polarization, which inhibits the Ca+ channel
- glucose: causes production of ATP in the cell, which inhibits the K(ATP) channel, which causes membrane depolarization, which opens the Ca+ channel, causing release of insulin in the blood
what is the role of insulin?
stimulate glucose uptake in adipose tissue and muscle, and stimulate glycogen synthesis in liver
Glut4 vs Glut2
Glut4:
- inducible by insulin
- not usually on surface but is recruited in the presence of insulin
- promotes glycogen synthesis (muscle) /lipogenesis (adipose tissue)
Glut2:
- non-inducible
- on liver
what is the role of the liver?
the keep glucose concentration at 5.5mM, and will do this by:
- fed-state: store glucose as glycogen
- fasting state: breaks down glycogen and gluconeogenesis
why are there so many glucose transporters?
- must be tailored to the needs of a tissue
- sugar specificity
- provides backup in case there is an issue
what is the ATP source during high-intensity exercise (at 6 secs, 10 secs, and 30-40 secs) and during prolonged duration?
- 6 secs: stored ATP in muscle
- 10 secs: from creatine ( P-creatine + ADP ➝ creatine + ATP)
- 30-40 secs: anaerobic glycolysis
- hours: aerobic glycolysis
What is the overview of the generation of ATP? What does each step produce and what controls each step?
- Glycolysis: generates 2 ATPs, 2 NADH, 2 Pyruvate out of 1 glucose, and does not require oxygen / stimulated by low ATP and inhibited by low NAD and high ATP
- Citric Acid Cycle: produces NADH and FADH2 out of acetyl-CoA / inhibited by high NADH
- Oxidative phosphorylation: produces ATP out of NADH, FADH2 and O2 / stimulated by low ATP, and inhibited by high ATP, low O2, and low NADH and FADH2
what is required for glycolysis to move forward? how is it replenished under different conditions (with and without O2)?
- NAD+ is required
- with O2, constantly replenished by oxidative phosphorylation
- without O2, can go through homolactic fermentation (production of lactic acid in muscle) or alcoholic fermentation in bacteria
What is the main source of ATP for cancer cells? What does this tell us?
glycolysis
- tells us that must use a lot of glucose since 17x less effective that oxidative phosphorylation
- they produce high amounts of pyruvate, acetyl-CoA, and lactic acid which is pumped out of the cancer cells by transporters
Which steps in glycolysis are the regulatory steps?
step 1 (glucose to G6P), step 3 (F6P to F1,6P), and step 10 (PEP to pyruvate)
Why is it important that glucose gets converted to glucose-6-phosphate?
- traps glucose in the cell (phosphorylated compounds do not transport readily)
- keeps the concentration of glucose in the cytoplasm low, which allows more glucose to be taken up passively
Compare hexokinase and glucokinase.
(catalyzed reaction, substrate specificity, tissue of prevalence, affinity constant, modulator, and metabolic consequence)
- catalyzed reaction: same reaction glucose + ATP → glucose-6-phosphate + ADP
- substrate specificity: hexoses vs glucose
- tissue of prevalence: all cell types vs liver
- affinity constant: ~0.1mM vs ~5mM
- modulator: glucose-6-phosphate vs glucokinase regulatory protein (GKRP)
- metabolic consequence: because hexokinase has a higher affinity for glucose, all cells will take up glucose first but it will saturate quickly, so the rest of the glucose will then be converted to glycogen in the liver by glucokinase
What is the role of glucokinase regulatory protein (GKRP)?
it is a binding partner that sequesters glucokinase in the nucleus when glucose levels are low and when glucose levels are high GKRP releases glucokinase to the cytoplasm
what does Phosphoglucose Isomerase do and what is it driven by?
equilibrium reaction ( glucose-6-phosphate ⇆ fructose-6-phosphate) that is driven by the abundance of substrates
what is the step that commits cells to metabolize glucose?
Conversion of fructose-6-phosphate into fructose-1,6-bisphosphate by PFK and ATP
what are the activators and inhibitors of PFK? How do these work?
- activators: AMP and F2,6P
- inhibitors: ATP, citrate
PFK has two states: T-state (inactive dimer) and R-state (active tetramer), AMP and F2,6P promotes R-state and ATP promotes T-state
Is ATP or AMP more potent at modulating PFK?
AMP
Role of Adenylate Kinase (ADK) and its biochemical consequence.
- it is an enzyme that regenerates ATP from two molecules of ADP ( 2 ATP ⇆ ATP + AMP )
- biochemical consequence: ADK keeps ATP abundant for exercise and also generates AMP, which activates PFK to create even more ATP
What principle allows for regulation of directionally in catabolic and anabolic pathways?
the pathway from the 1st to the 2nd metabolite must be different from the pathway from the 2nd to the 1st metabolite
