biochemical foundations exam 1

Purpose of glycolysis

Convert glucose into pyruvate and ATP as an effort to obtain energy

Where does glycolysis take place

cytosol/cytoplasm of the cell

Where does glycolysis take place

Can occur in:

• RBC

• All organs (includes heart, kidney, brain)

• Primarily the liver

• Muscles

Steps of glycolysis

1. Glucose → G6P via hexokinase/glucokinase

2. G6P → F6P via phosphoglucoisomerase

3. F6P → F16BP via phosphofructokinase

4. F16BP → DHAP + G3P via fructose bisphosphate aldolase

5. DHAP → G3P via triose phosphate isomerase

6. 2 G3P → 2 1,3 BPG via G3P DH

7. 2 1,3 BGP → 2 3-PG via phosphoglycerate kinase

8. 2 3-PG → 2 2-PG via phosphoglycerate mutase

9. 2 2-PG → PEP via enolase

10. PEP → pyruvate via pyruvate kinase

Glycolysis product net yield

2 ATP (4 made - 2 spent)

2 NADH

2 Pyruvate

Rate limiting step of glycolysis

Rate limiting step: Fructose-6-phosphate → Fructose-1,6-bisphosphate (PFK-1 + ATP)

What steps in glycolysis are irreversible

Step 1: Glucose → Glucose-6-phosphate (Hexokinase/Glucokinase + ATP)

traps glucose in cell, prevents it from leaving

Step 3: PFK-1 (ΔG = -14.2 kJ/mol) ⭐ MOST IMPORTANT

Primary control point for the ENTIRE pathway

Step 10: PEP → Pyruvate (Pyruvate kinase, produces ATP)

Second ATP generation, final step

Which steps require ATP

Glucose → G6P via hexokinase/glucokinase

• Step 1: -1 ATP

F6P → F16BP via phosphofructokinase

• Step 3: -1 ATP

Which steps produce ATP

2 1,3 BGP → 2 3-PG via phosphoglycerate kinase

• Step 7: +2 ATP (×2 because 2 G3P)

PEP → pyruvate via pyruvate kinase

• Step 10: +2 ATP (×2 because 2 PEP)

Describe PFK-1 regulation (activators)

• ↑ AMP/ADP = “We need energy!”

• ↑ Fructose-2,6-bisphosphate (F-2,6-BP) = Most potent activator

  • Made by PFK-2

  • High in fed state (insulin)

• ↑ Pi (inorganic phosphate)

• ↑ NAD+ = coenzyme used

Describe PFK-1 regulation (inhibitors)

• ↑ ATP = "We have plenty of energy"

• ↑ Citrate = "TCA cycle is backed up, we're good"

• ↑ H+ (low pH) = "Too much lactate being made"

  • Lactate directly inhibits PFK-1

  • In the cori cycle, pyruvate is made into lactate

• Decreases NAD+ []

• ↑ NADH (product of glycolysis

Describe hormonal regulation

Insulin (fed state): Activates PFK-2 → ↑ F-2,6-BP → ↑ Glycolysis

• F26BP allosterically activates PFK-1

• F26BP OFF

Glucagon (fasting): Inhibits PFK-2 → ↓ F-2,6-BP → ↓ Glycolysis

• PKA phosphorylates FBPase-2, activating it = F26BP inactive

Describe pyruvate kinase regulation (activator)

F16BP

Describe pyruvate kinase regulation (inhibitor)

• ATP

• Alanine

• Acetyl coA

Describe hexokinase inhibitor

high G6P

What is the purpose of gluconeogenesis?

To regenerate glucose in conditions of low glucose and high energy

Where does gluconeogenesis take place?

ER lumen and the mitochondrial matrix in the liver and kidney cell