Pentose Phosphate Pathway (PPP)

• the pentose phosphate pathway (PPP) is an alternative to glycolysis, which generates NADPH and/or ribose-5-phosphate from G6P
• NAD+ is used as an oxidant (and is kept in higher concentrations than its reduced form, NADH), while NADPH is used as a reductant (and is kept in higher concentrations than its oxidized form, NADP+)
• PPP occurs in two phases
• Step 1 of Phase 1 of PPP

  • redox reaction, where G6P is oxidized and NADP+ is reduced
  • the electron of question is transferred in a hydride transfer from G6P to NADP+

  
• Step 2 of Phase 1 of PPP

  • hydrolysis reaction at an ester
  • opens up the ring
  • the carbonyl carbon becomes C1

  
• Step 3 of PPP Phase 1

  • redox reaction, where 6-phosphogluconate is oxidized and NADP+ is reduced
  • from 6 carbons to 5 carbons
  • mechanism: first oxidation to form the carbonyl, then decarboxylation to remove the CO2

  
• transketolase transfers or carries 2 carbons

  transaldolase transfers or carries 3 carbons

  
• Fill in the labels (what processes can these molecules feed into?)

  A) nucleotide biosynthesis

  B) glycolysis or gluconeogenesis

  C) glycolysis or gluconeogenesis

  
• General biochemistry/enzyme method used in isomerization of Ru5P?

  Deprotonate the alpha-carbon to make an enolate intermediate.

  
• Thiamine pyrophosphate (TPP) is also used as a cofactor in the conversion of pyruvate to acetyl CoA (PDH complex)
• transaldolase uses covalent catalysis and creates a Schiff base to act as an electron sink

  
• Thiamine pyrophosphate (TPP) acts is a cofactor for transketolase, where it acts as an electron sink and a 2-carbon carrier

  
• Why do transaldolase and transketolase have to use different electron sink methods?

  Because the location of the sink needed differs! We need a different atom to hold the electrons, and so they need different electron sinks
• transaldolase creates a schiff base to use as an electron base
• Phase 1 of PPP will create NADPH, and Phase 2 creates R5P. But often we need NADPH more than we need R5P, so to avoid buildup of R5P, we ultimately create the glycolytic intermediates GAP and F6P (and these can even in turn feed back into PPP!)

  
• But what if we do want R5P from PPP? Remember that Phase 2 is completely reversible! So we can just go back from the glycolytic intermediates form (F6P, GAP) to make the wanted R5P again
• main point of regulation control for PPP is at the first enzyme! this first step is the committed step, and is regulated by G6P and NADP+ (the substrates or reactants!), which will activate it