Glucose-2

Why is trapping the glc in the cell important?

The amount of free glc stays low and this allows glc intake without ATP expenditure

Which enzyme, between hexokinase and glucokinase, has a higher affinity for glc?

Hexokinase

What’s an example of metabolic pathway regulation?

Product inhibition

What is product inhibition?

Enzyme inhibition that happens when a product accumulates and competes for the active site

What is a good example of product inhibition?

G-6-P with hexokinase

What is the 2nd step of glycolysis?

G-6-P ⇌ F-6-P

What enzyme allows the 2nd step?

Phosphoglucose isomerase

How is a reaction at equilibrium maintained?

It is driven by the abundance of substrates (Le Châtelier)

What is the 3rd step of glycolysis?

F-6-P → F-1,6-BP

What enzyme allows the 3rd step?

PFK1

What makes this second irreversible step the one that commits cells to metabolize glc?

F-6-P is not used in other pathways unlike G-6-P

What are PFK1 activators?

AMP and F-2,6-BP

What is a PFK1 inhibitor?

ATP (downstream!)

What makes AMP, F-1,6-BP and ATP downstream regulators?

They are allosteric regulators (regulatory binding site vs active catalytic site)

What is the 4th step of glycolysis?

FBP ⇌ GAP + DHAP

What is the 5th step of glycolysis?

GAP ⇌ DHAP

Why is DHAP most abundant in cells even while trying to maintain equilibrium?

Because GAP is siphons by glycolysis (2 GAP PER Glc)

What do the previous steps combine into?

The investment phase

Why is it called the investment phase?

Because 2 ATP molecules are used in it

What are the simple steps of that phase?

1. Phosphorylation

2. Isomerization

3. Phosphorylation

4. Cleavage

What do the next steps combine into?

The “pay-off'“ phase

Why’s it called the pay off phase?

Because 2 ATP molecules are generated

What is the first step of the pay off phase?

GAP → 3PG + NADH + ATP

Why is this fisrt step an example of substrate channeling?

Because a high E intermediate is passed along GAPDH and PGK

What is the 2nd step of the pay off phase?

3PG → 2PG

What enzyme facilitates this 2nd step?

Mutase

What is the 3rd step of the pay off phase?

2PG → PEP

What enzyme facilitates this 3rd step?

Enolase

What is the last step of glycolysis which is also the last committed step?

PEP → Pyruvate

What is the enzyme that facilitates this last step?

PK

What are PK activators?

FBP(upstream) and PEP (downstream)

What is a PK inhibitor?

ATP (if enough, why make more?)

What molecule is needed if not O₂?

NAD⁺

What enzyme allows NAD⁺ regeneration?

LDH

How does LDH work in the muscles?

Py+ NADH → Lac + NAD⁺

LDH and cancer

Overexpressed in cancer cells

How does LDH work in the liver?

Lact. → Pyr.

Why does lactate need to be eliminated from the blood?

low pH → inhibit PFK1 → slow glycolysis

What transporter allows the efflux of lactate from muscles?

MCT4

What transporter allows the influx of lactate into the liver?

MCT1

What’s this cycle of lactate efflux and influx called?

The Cori cycle

What’s the Warburg Effect ?

When cancer cells undergo aerobic glycolysis in the presence of sufficient oxygen

What does unselective aerobic glycolysis result into?

The accumulation of lactate from pyruvate → 16X less effectiveness bc 5% Ox. Phos.