HLTH 217 - CHP 16 glycolysis

Why is glucose prominent in fuel?

Available for all biochem systems, most stable hexose, low tendency to nonenzyematically glycoslyate proteins

What is needed to catalyze reaction 1 in the investment stage?

Mg2+ or Mn2+ as cofactors

What is the commitment step in glycolysis

Step 3 — the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate
Enzyme: Phosphofructokinase (PFK)

What are all the irreversible steps in glycolysis 

step 1, 3, 5/last step in yielding stage , this is where regulation occurs

What are the regulatory steps of glycolysis?

Reactions catalyzed by hexokinase, phosphofructokinase, pyruvate kinase

Glycolysis regulation in muscles

It typically provides atp to power muscle contraction and is stimulated when ATP falls.

High ATP impact on PFK

ATP binds to allosteric site → enzyme inhibited SO Glycolysis slows down 

High AMP impact on PFK

AMP competes with ATP but doesn’t inhibit, binds to PFK allosteric site activating it and speeding up glycolysis

pH effects on PFK

When muscles work hard without enough oxygen, they produce lactic acid, which lowers pH (makes things more acidic).
Low pH strengthens ATP’s inhibition of PFK.
This helps slow down glycolysis, preventing too much acid buildup that could damage muscle cells.

What happens when there is too much G6P

inhibits hexokinase. So, when PFK stops, it sends a signal upstream that tells hexokinase to stop too.

Pyruvate Kinase regulating glycolysis

If excess ATP, no need to make more so pyruvate kinase is inhibited

What happens if there is high pyruvate levels?

Alanine gets made through an amine group being added to pyruvate, then alanine inhibits pyruvate kinase

What happens if excess fructose 16 biphosphate?

Stimulates pyruvate kinase to keep up

Liver glycolysis - phosphofructokinase

Glycolysis firstly in the liver doesn’t need the sudden ATP like muscle contraction but rather is used to make carbon skeletons for biosynthesis (so like fatty acids, amino acids etc). When there is high level of citrate, (from citrate acid cycle) it inhibits phosphofructokinase because there is no need for more glucose/energy.

high citrate = inhibition of PFK, slowing glycolysis.

Liver glycolysis - glucokinase

same role as hexokinase (phosphorylates glucose).

When glucose is low, Glucosekinase regulatory protein binds and traps glucokinase in the nucleus, so it can’t work.

When glucose is high, glucokinase is released to the cytoplasm to phosphorylate glucose.

Why does glucokinase only work when glucose is abundant?

Because it has a high Km (low affinity) — it needs lots of glucose to work effectively.

Is glucokinase inhibited by glucose 6-phosphate (its product)?

No — it’s not inhibited, unlike hexokinase.

Pyruvate Kinase in liver glycolysis regulation 

• When blood glucose is low, the liver shouldn’t be using glucose for its own glycolysis.

• So glucagon (the low-blood-sugar hormone) signals through cAMP to phosphorylate (turn off) liver pyruvate kinase.

Q: What molecule inhibits only the liver (L) form of pyruvate kinase?

A: Alanine, because it signals that biosynthetic building blocks are available.

Q: What happens to liver pyruvate kinase when blood glucose is low?

A: Glucagon → cAMP pathway → phosphorylates and inactivates it, stopping glycolysis in the liver.

Q: Why is liver pyruvate kinase turned off when glucose is low?

A: To prevent the liver from using glucose, saving it for the brain and muscles.

Lactose Intolerance

inability to digest lactose due to the lack of enzyme lactase (lactose is sugar in milk)

What happens to lactose when lactase is low?

it cannot be absorbed and is instead fermented by gut bacteria.

What are the fermentation products of undigested lactose?

Lactate, methane, and hydrogen gas.

Do most mammals keep lactase activity after weaning?

No, most lose lactase activity after weaning.

Q: Why can many Northern Europeans digest milk as adults?

A: They have a genetic mutation that prevents the decline of lactase activity after weaning.

Why was the lactase-persistence mutation beneficial?

It allowed adults to digest milk, providing a reliable food source during dairy farming.