BCH2MBC

Module 3: Central Carbon Metabolism

Glycolysis Overview

• Process: Glucose → Pyruvate, net gain of 2 ATP & 2 NADH.

• Phases: 10 enzymatic reactions split into two phases:

  • Preparatory: ATP consumed

  • Payoff: ATP produced

• Key Regulatory Enzymes:

  • Hexokinase

  • Phosphofructokinase (PFK)

  • Pyruvate Kinase

Regulation of Glycolysis

• Hexokinase (Step 1): Phosphorylates glucose, traps it in the cell.

• Phosphofructokinase (PFK) (Step 3): First committed step, regulated by:

  • ATP (inhibition)

  • AMP (activation)

  • Citrate (inhibition)

  • Fructose-2,6-bisphosphate (activation)

• Pyruvate Kinase (Step 10): Converts PEP to pyruvate, regulated by:

  • ATP (inhibition)

  • Acetyl-CoA (activation)

  • Fructose-1,6-bisphosphate (activation)

  • Alanine (inhibition)

Fates of Pyruvate

• With Oxygen: Converted to acetyl-CoA for TCA cycle.

• Without Oxygen: Converted to lactate (in animals) or ethanol (in yeast).

Gluconeogenesis

• Location: Primarily in the liver, producing glucose from non-carbohydrate sources.

• Function: Opposes glycolysis, shares reversible steps but bypasses irreversible ones with specific enzymes.

Systemic Regulation by Insulin & Glucagon

• Insulin (high glucose): Activates glycolysis, glycogen synthesis.

• Glucagon (low glucose): Promotes gluconeogenesis, glycogen breakdown.

• Tissue-specific Enzymes: (e.g., Hexokinase IV in the liver) aid differential regulation.

Diabetes & Metabolic Dysregulation

• Type I: Insulin deficiency, reliance on fat metabolism.

• Type II: Insulin resistance, increased glucose levels despite normal or high insulin.

Note: "–|" represents inhibition and "–>" represents activation.