Pentose Phosphate Pathway

Overview

• Importance: Essential for synthesis reactions such as neurotransmitters, lipids, cholesterol, nucleotides, and also crucial for free radical reactions.
• Pathway Steps: Involves the conversion of glucose into different intermediates for synthesis and energy production.

Initial Steps

1. Glucose Uptake:

   • Glucose enters liver cells via GLUT2 transporters.
   • Enzyme: Glucokinase converts glucose to glucose 6-phosphate (G6P) by adding a phosphate group from ATP.

2. Pathway Options for G6P:

   • Glycolysis: G6P can enter glycolysis, leading to pyruvate formation and ATP production (4 ATP gross, 2 ATP net).
   • Pentose Phosphate Pathway (PPP): G6P can also enter the pentose phosphate pathway.

Pentose Phosphate Pathway

Key Steps

1. Conversion of G6P to 6-Phosphogluconolactone:

   • Enzyme: Glucose 6-phosphate dehydrogenase.
   • Uses NADP⁺, producing NADPH.

2. Conversion to 6-Phosphogluconate:

   • Enzyme: Lactonase.
   • Involves the addition of water.

3. Formation of Ribulose 5-Phosphate:

   • Enzyme: 6-Phosphogluconate dehydrogenase.
   • Produces NADPH and CO2.
   • Ribulose 5-phosphate is a 5-carbon molecule.

Fates of Ribulose 5-Phosphate

• Conversion to Ribose 5-Phosphate:

  • Enzyme: Isomerase (ketone to aldehyde).
  • Important for nucleotide synthesis (DNA, RNA).

• Conversion to Xylulose 5-Phosphate:

  • Enzyme: Epimerase.
  • Involves diastereomer changes, differing in chirality at one carbon.

Carbon Shuffling

1. Transketolase Reactions:

   • Transfers 2-carbon units.
   • Converts Xylulose 5-phosphate and Ribose 5-phosphate to Glyceraldehyde 3-phosphate and Sedoheptulose 7-phosphate.

2. Transaldolase Reaction:

   • Transfers 3-carbon units.
   • Converts Glyceraldehyde 3-phosphate and Sedoheptulose 7-phosphate to Fructose 6-phosphate and Erythrose 4-phosphate.

3. Further Reactions:

   • Xylulose 5-phosphate and Erythrose 4-phosphate are converted into Glyceraldehyde 3-phosphate and Fructose 6-phosphate.

Phases of PPP

• Oxidative Phase:

  • Produces NADPH and Ribose 5-phosphate.
  • Steps include the conversion of G6P through to Ribose 5-phosphate and Xylulose 5-phosphate.

• Non-Oxidative Phase:

  • Involves carbon shuffling reactions.
  • Allows the production of Ribose 5-phosphate without NADPH formation and vice versa using glycolytic intermediates.

Importance of Key Molecules

• NADPH:

  • Acts as a reducing agent in biosynthetic reactions like fatty acid and cholesterol synthesis, nucleotide production, and neurotransmitter synthesis.
  • Important for free radical reactions as an antioxidant.

• Ribose 5-Phosphate:

  • Crucial for nucleotide synthesis (DNA, RNA, ATP, NAD⁺, FAD, Coenzyme A).

Regulation and Implications

• Enzyme Deficiencies: Deficiency in glucose 6-phosphate dehydrogenase can lead to hemolytic anemia and Heinz body formation.
• Interconnected Pathways: The PPP is linked with glycolysis and gluconeogenesis, allowing flexibility based on cellular needs.

The lecture highlighted the significance of the pentose phosphate pathway in cellular metabolism, emphasizing its roles in synthesis and protection against oxidative stress. The upcoming session promises to delve deeper into regulatory mechanisms and clinical implications.