3/31/2017

Objectives
• Discuss the enzymes, co-factors, regulation and
significance of the Pentose Phosphate Pathway.
• Discuss how the PPP adjusts depending on
certain cellular requirements
• Discuss the role of PPP in detoxification
processes of the cell
CHEM 160
PENTOSE PHOSPHATE
PATHWAY

Glucose Metabolism Glucose Metabolism

 Storage
can be stored in polymeric form
(starch, glycogen)
 Glycolysis
Generates energy via oxidation
of glucose
 Synthesis of structural
polysaccharides
e.g. cellwall of plants, bacteria
and fungi
 Pentose phosphate pathway

Pentose Phosphate Pathway Pentose Phosphate Pathway

Functions:
Also called  To generate reducing power in the form of
NADPH
 Hexose Monophosphate Shunt - universal reductant in anabolic pathways
o Fatty acid biosynthesis
 Phosphogluconate Pathway o Cholesterol biosynthesis
o Neurotransmitter biosynthesis
o Nucleotide biosynthesis

- Detoxification- reduction of glutathione

1
 3/31/2017

Pentose Phosphate Pathway Pentose Phosphate Pathway

Functions:
• Occurs in the cytosol of cells in the following
 To generate pentoses from hexoses (D-ribose- tissues:
5-P)
- essential component of RNA, DNA, ATP, NADH,
FAD and CoA
 To convert excess pentoses back to hexoses for
oxidation via glycolysis

Stages of PPP General

1. Oxidative Stage
scheme
• Oxidative generation of NADPH
of PPP
2. Non-oxidative Stage
• Interconversion of 3, 4, 5, 6 and 7-carbon
sugars that results in the synthesis of 5-C
sugars
• Serves as link of PPP to glycolysis

Oxidative Stage: Reaction 1 Oxidative Stage: Reaction 2

• Main regulatory step in PPP

• Hydrolysis of the lactone to yield carboxylate

2
 3/31/2017

Oxidative Stage: Reaction 3 Oxidative Stage: Net Reaction

Glucose-6-P + 2 NADP+ + H2O

⬇
Ribulose-5-P + 2 NADPH,H+ + CO2

• Oxidative decarboxylation to yield ribulose-5-P

and CO2

Regulation of Oxidative Stage Non-oxidative Stage

Non-oxidative Stage Non-oxidative Stage

• Transketolase catalyzes transfer of two-carbon

units

3
 3/31/2017

Non-oxidative Stage Non-oxidative Stage

• Transaldolase catalyzes transfer of three-carbon

units

Rearrangements of C skeletons Overall Reaction of the PPP

C5 + C5 ⇌ C3 + C7 3 Glucose-6-P + 6 NADP+ + 3 H2O

C3 + C7 ⇌ C6 + C4
C4 + C5 ⇌ C6 + C3
⬇
6 NADPH,H+ + 3 CO2 + 2 Fructose-6-P
3C5 ⇌ 2C6 + C3 + Glyceraldehyde-3-P

3 ribose-5-P ⇌ 2 fructose-6-P + glyceraldehyde-3-P

Note that the reactions are REVERSIBLE.

Mode 1: Both NADPH and Ribose-5-P

are needed
• Only the oxidative phase is active
Glucose-6-P + 2 NADP+ + H2O
MODES OF THE PENTOSE
⬇
PHOSPHATE PATHWAY Ribulose-5-P + 2 NADPH,H+ + CO2

Isomerizes to Used in fatty

ribose-5-P for nucleic acid synthesis
acid synthesis

4
 3/31/2017

Mode 2: Only Ribose-5-P is needed Mode 3: Only NADPH is needed

• In adipose tissues for synthesis of fatty acids
• In actively dividing cells • Both oxidative and non-oxidative phases are
• Reverse of the non-oxidative stage active
• While NADPH is generated in the oxidative
• 2C6 + C3 ⇌ 3C5
phase, ribose-5-P enters the non-oxidative
DHAP phase for re-generation of Glc-6-P
Glc-6-P → Frc-6-P → Frc-1,6-bP ⇅
Glyceraldehyde-
3-P
Ribose-5-P

Mode 3: Only NADPH is needed

GLUTATHIONE AND PENTOSE

PHOSPHATE PATHWAY

Glutathione GSH as an Antioxidant

• g-glutamylcysteylglycine (reduced form)

• Essential for maintaining the normal structure
of red blood cells (iron is maintained in the
ferrous state)
• Detoxifies reactive oxygen species (peroxides)

5
 3/31/2017

Detoxification of Peroxides Glc-6-P dH Deficiency

glutathione peroxidase 2 GSSG +
2 GSH + ROOH • Insufficient production of NADPH which results
H2O + ROH eventually into insufficient GSH
• Cells cannot fight oxidative stress
• Cells are susceptible to hemolysis (hemolytic
anemia)

Disulfide form of glutathione (oxidized)