PENTOSE PHOSPHATE PATHWAY

Definition

The pentose phosphate pathway is a metabolic pathway that runs alongside glycolysis.

  • it doesn’t make or produce ATP

  • occurs in all cells

  • the products are important for producing reducing power for anabolic processes

What does it produce

  • Pentoses = 5 carbon sugars

    • Produce ribose‑5‑phosphate (for nucleotide and DNA/RNA synthesis)

    • Pentoses are responsible for making some biomolecules

      • RNA, DNA, ATP, ADP, AMP and Coenzymes

  • Produce NADPH (for reductive biosynthesis and protection against oxidative damage)

Location:

  • it occurs in the cytosol

    • active in the adipose tissue

      • as there are anabolic processes happening there

NADPH PRODUCTION AND USAGE

Structure:

  • It has a phosphate attached to it

  • it can be reduced and oxidised between 2 forms

    • NADP+

    • NADPH (anabolic process)

  • THIS IS NOT NADH

    • which is produced in the Krebs cycle and in glycolysis

    • used in catabolic processes

Importance of NADPH:

  • Critical for biosynthetic reactions, including fatty acid synthesis and detoxification processes in macrophages.

  • Used in the synthesis of:

    • cholesterol

    • nucleotides

    • neuro-transmitters

    • macrophages

    • reducing agent in detoxification

    • fatty acids

Synthesis of Pentoses (5 carbon sugars)

it is in the form of ribose 5 phosphate

These are important in:

  • ATP

  • CoA

  • RNA

  • FAD

  • NADH

  • DNA


Two Stages:

Oxidative Stage:

  • Converts Glucose 6-phosphate into Ribulose 5-phosphate

  • P

  • roducing NADPH x2

  • releasing CO₂

Non-Oxidative Stage:

  • This is when we rearrange the carbon skeletons of these molecules

    • 1st ribulose-5-phosphate is converted into ribose-5-phosphate

      • important for biomolecules

if there is an excess of ribose-5-phospate as we have enough biomolecules

  • then the ribose-5-phosphate can be converted into metabolites or intermediates of glycolysis

    • that is through enzymes

      • transketolases

        • these will move 2 carbons from one molecule to another

      • transaldolases

        • these transfer 3 carbons from one molecule to another

Summery

  • Interconversion of ribose-5-phosphate and glycolytic intermediates

    • via transketolase and transaldolase

  • allows excess ribose-5-phosphate to be utilized in glucose degradation pathways.

This shows that some of the products of transketolase and transaldolase can be used in glycolysis

  • fructose 6-phoshate

  • glyceraldehyde 3-phopshate

CONTROL OF THE PENTOSE PHOSPHATE PATHWAY

The PPP is regulated by the enzyme glucose-6-phosphate dehydrogenase.

  • this makes sense as it is the first enzyme in the pathway

  • in the oxidative stage

Glucose 6-phosphate Dehydrogenase (G6PD):

  • its a homodimer which is a protein made up of 2 identical subunits that bind together

  • allosterically regulated

    • by NADPH (its product)

    • it is a ihibitor

THE NON_OXIDATIVE STAGE IS BASED ON THE AVAILABILITY OF SUBSTRATE

Examples of how the Oxidative and non oxidative stage are regulated

- for this w want to know why these processes are behaving in the way that they are

BALANCED NEED FOR NADPH AND PENTOSES

  • oxidative stage as NDPH is being produced

  • and then ribose 5 -phosphate need to be converted into biomolecules

LOTS OF PENTOSES

  • there are cells that are rapidly dividing

    • so we need a lot of nucleotides

      • to make DNA

  • glucose 6-phosphate from glycolysis form the glycolytic intermediates

  • which can be rearranged into a lot of 5 carbon pentoses

    • made into DNA

NEED A LOT OF NADPH

  • in adipose tissue

    • NADPH is needed for anabolic processes and synthesis of fatty acids

  • the NADPH is produced in the oxidative stage

    • which ends in ribose 5-phosphate

  • we can rearrange ribose 5-phosphate through the non-oxidative stage

    • to produce intermediates which can make more glucose-6-phosphate

CLINICAL IMPACT OF PPP DEFICIENCY

  • Glucose-6-phosphate Dehydrogenase Deficiency:
      - Common genetic disorder affecting sugar metabolism; associated with hemolytic anemia due to oxidative stress.
      - Individuals may show sensitivity to certain drugs, such as primaquine (used for malaria).

  • there are so many ppl who have this as deficiency in the enzyme can help ppl with malaria

SUMMARY

  • Understand how gluconeogenesis and the pentose phosphate pathway generate glucose and NADPH, respectively.

  • Recognize the importance of regulation in metabolic pathways for maintaining homeostasis.