Chapter 20: (PPT) Pentose Phosphate Pathway

Overview of the Pentose Phosphate Pathway

• The Pentose Phosphate Pathway (PPP) is essential in all organisms, generating NADPH and pentoses.

• It serves two main functions:

  • Generating NADPH for reductive biosynthesis and protection against oxidative stress.

  • Synthesizing ribose-5-phosphate, necessary for nucleotide synthesis.

Phases of the Pentose Phosphate Pathway

• The PPP consists of two phases:

  1. Oxidative Phase:

  • Converts glucose-6-phosphate to ribulose-5-phosphate.

  • Reaction:
    ext{Glucose 6-phosphate} + 2 ext{NADP}^+ + ext{H}2 ext{O} \rightarrow ext{Ribulose 5-phosphate} + 2 ext{NADPH} + 2 ext{H}^+ + ext{CO}2

  • Yields 2 molecules of NADPH and CO₂.

  1. Non-Oxidative Phase:

  • Involves interconversion of sugar phosphates (3, 4, 5, 6, 7 carbons).

  • Regenerates ribulose-1,5-bisphosphate for the Calvin cycle.

Importance of NADPH

• Pathways Requiring NADPH:

  • Fatty acid biosynthesis.

  • Cholesterol biosynthesis.

  • Neurotransmitter and nucleotide biosynthesis.

  • Protection from oxidative stress (reducing oxidized glutathione).

  • Cytochrome P450 metabolism.

Enzymatic Steps in the Oxidative Phase

• Key enzymes involved:

  • Glucose 6-Phosphate Dehydrogenase (G6PD):

  • Initiates the oxidative phase by converting glucose 6-phosphate into 6-phosphoglucono-δ-lactone, producing NADPH.

  • Lactonase:

  • Hydrolyzes 6-phosphoglucono-δ-lactone to 6-phosphogluconate.

  • 6-Phosphogluconate Dehydrogenase:

  • Converts 6-phosphogluconate to ribulose 5-phosphate, producing another NADPH and CO₂.

Linking the Pentose Phosphate Pathway and Glycolysis

• Transketolase and Transaldolase:

  • Connect the PPP with glycolysis by facilitating conversion between different sugar phosphates.

  • Convert pentoses into hexoses and triose sugars, allowing the flow of intermediates based on cellular needs.

Variations in Metabolism Modes

• The PPP can adapt to four distinct modes based on cell requirements for NADPH, ribose 5-phosphate, and ATP:

  1. Mode 1: Much more ribose 5-phosphate is needed.

  • Glucose 6-phosphate → 6 ribose 5-phosphate.

  1. Mode 2: Balanced need for NADPH and ribose 5-phosphate.

  • ext{Glucose 6-phosphate} + 2 ext{NADP}^+ + ext{H}2 ext{O} \rightarrow ext{Ribose 5-phosphate} + 2 ext{NADPH} + 2 ext{H}^+ + ext{CO}2

  1. Mode 3: High demand for NADPH.

  • Glucose 6-phosphate is oxidized to NADPH and ribulose 5-phosphate.

  1. Mode 4: Both NADPH and ribose 5-phosphate are needed.

  • Pyruvate is generated alongside other metabolites.

Cellular Functions Relating to the Pentose Phosphate Pathway

• Rapidly Dividing Cells: Require increased ribose 5-phosphate and NADPH for nucleotide and lipid synthesis.

• Glucose 6-Phosphate Dehydrogenase: Key to reducing oxidative stress in cells. Deficiency in G6PD may confer malaria resistance amongst some populations due to decreased parasite survival.

Summary of Key Points

• The pentose phosphate pathway plays a crucial role in cellular metabolism by providing NADPH and ribose-5-phosphate.

• Enzymatic steps involving G6PD, transketolase, and transaldolase link this pathway to glycolysis, adapting to meet the metabolic demands of the cell.

• Understanding this pathway is essential for insights into cellular growth, antioxidant defense, and metabolic disease.

CLASS NOTES (4/4)

S2: .

S3: Glucose goes to Glucose 6 phosphate at the very beginning of glycolysis. The second phase, the nonoxidative interconvention of three-, four-, five-, six-, and seven- carbon sugars. (You don’t need to know all the conversions/structures)

S4: To make neurotransmitters, we need NADPH…

S9: We can create pentoses, and hexoses can go off into glycolysis. Feeds into NADPH for a more efficient use of molecules.

S10: (don’t need to know these images)

S11: …

S12: Rearranging sugars as we see fit in order to keep feeding into glycolysis

S13: …

S14: …

S15: …

S16: TPP gets released for the next rxn cycle

S17: (image, not as much on the exam)

S18: … (skipped)

S23: Why do we need the Pentase Phosphate Pathway? It switches gears depending on which condition is going on inside of the cell. It can operate in FOUR MODES.

S24: (image) we want to focus on getting that NADPH in use so it can be fed back into the pathway.

S25: MODE 1: Much more Ribose 5-phosphate than NADPH is required.

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