1. PENTOSE PHOSPHATE PATHWAY (Hexose monophosphate pathway)
Learning objectives:
List the two phases (oxidative and non-oxidative) of the
pentose phosphate pathway
List key enzymes involved in the pathway
Glucose 6-phosphate dehydrogenase
Transketolase
Transaldolase
List key compounds involved in the pathway:
Glucose 6-phosphate
NADPH
Ribose 5-phosphate
Glyceraldehyde 3-phosphate
Fructose 6-phosphate
Discuss functions of the pentose phosphate pathway in cell metabolism

2. The “reducing power” is NADPH
The cell needs “reducing power” for biosynthesis and protection against
oxidative stress.
The “reducing power” is NADPH
:H-
H H
NAD NADP NADPH

3. The cell needs ribose 5-phosphate for synthesis of nucleotides used in
DNA, RNA, NAD+, NADP+, FAD, and Coenzyme A
CH2OH Ι
H - C – OH
H – C – OH
CH2OPO32-
Ribose 5-phosphate
PO32--OH2 OH O
H H H H
OH OH
Ribose 5-phosphate
The pentose phosphate pathways provides both NADPH and ribose 5-phosphate

4. + lactonase
Phosphopentose
epimerase
CO2
Ribose 5-phosphate
isomerase

5. Glucose 6-phosphate
dehydrogenase
CH2OPO32-
CH2OPO32- O O H H H H H
+ NADP+
O + NADPH + H+
OH H
OH H OH OH OH
H OH
H OH
Glucose 6-phosphate
6-Phosphoglucono-δ-lactone
COO- Ι
H – C – OH
HO – C – H
CH2OPO32-
6-Phosphogluconate
CH2OPO32- O
Lactonase H H
O + H2O
+ H+
OH H OH
H OH
6-Phosphoglucono-δ-lactone

6. COO- Ι
H – C – OH
HO – C – H
CH2OPO32-
6-Phosphogluconate
CH2OH Ι
C – O
H – C – OH + NADPH + CO2
H – C – OH
CH2OPO32-
Ribulose 5-phosphate
6-Phosphogluconate
dehydrogenase
+ NADP+

7. Stoichiometry for oxidative phase of pentose phosphate pathway
Glucose 6-phosphate + 2 NADP+ + H2O →
Ribulose 5-phosphate + 2 NADPH + 2 H+ + CO2

8. CHO Ι
H - C – OH
H – C – OH
CH2OPO32-
Ribose 5-phosphate
Ribose 5-phosphate
isomerase
CH2OH Ι
C – O
H – C – OH
CH2OPO32-
Ribulose 5-phosphate
CH2OH Ι
C – O
HO – C – H
H – C – OH
CH2OPO32-
Xylulose 5-phosphate
Phosphopentose
epimerase

9. CHO Ι
H - C – OH
H – C – OH
CH2OPO32-
Ribose 5-phosphate
CH2OH Ι
C – O
HO – C – H
H - C – OH
H – C – OH
CH2OPO32-
Sedoheptulose 7-phosphate
Transketolase
CH2OH Ι
C – O
HO – C – H
H – C – OH
CH2OPO32-
Xylulose 5-phosphate + +
CHO Ι
H – C – OH
CH2OPO32-
Glyceraldehyde 3-phosphate

10. CHO Ι
H – C – OH
CH2OPO32-
Erythrose 4-phosphate
CH2OH Ι
C – O
HO – C – H
H - C – OH
H – C – OH
CH2OPO32-
Sedoheptulose 7-phosphate
Transaldolase +
CH2OH Ι
C – O
HO – C – H
H – C – OH
CH2OPO32-
Fructose 6-phosphate +
CHO Ι
H – C – OH
CH2OPO32-
Glyceraldehyde 3-phosphate

11. CHO Ι
H – C – OH
CH2OPO32-
Erythrose 4-phosphate
CH2OH Ι
C – O
HO – C – H
H – C – OH
CH2OPO32-
Fructose 6-phosphate
Transketolase +
CH2OH Ι
C – O
HO – C – H
H – C – OH
CH2OPO32-
Xylulose 5-phosphate +
CHO Ι
H – C – OH
CH2OPO32-
Glyceraldehyde 3-phosphate

12. Stoichiometry for non-oxidative phase of pentose phosphate pathway
Xylulose
5-phosphate
Fructose
6-phosphate
Transketolase
Xylulose
5-phosphate
Sedoheptulose
7-phosphate
Glyceraldehyde
3-phosphate
Erythrose
4-phosphate
Glyceraldehyde
3-phosphate
Transaldolase
Transketolase
Ribose
5-phosphate
Fructose
6-phosphate
Stoichiometry for non-oxidative phase of pentose phosphate pathway
3 Pentose 5-phosphate Fructose 6-phosphate + Glyceraldehyde 3-phosphate
Stoichiometry for the whole pentose phosphate pathway
3 Glucose 6-phosphate + 6 NADP+ + 3 H2O →
2 Fructose 6-phosphate + Glyceraldehyde 3-phosphate + 6 NADPH + 6H+ + 3CO2

13. - + Glucose 6-phosphate dehydrogenase CH2OPO32- CH2OPO32- O O H H H H
+ NADP+
O + NADPH + H+
OH H
OH H OH OH OH
H OH
H OH
Glucose 6-phosphate
6-Phosphoglucono-δ-lactone
The first step in the pentose phosphate pathway is the main regulatory step
of the pathway
NADPH (Competitive inhibitor of the enzyme)
Insulin (enhances expression of the enzyme leading to
enhanced flux through pathway in the well-fed state) - +

14. Different outcomes of the pentose phosphate pathway
The needs for NADPH and ribose 5-phosphate are balanced:
Glucose 6-phosphate + 2 NADP+ + H2O → Ribose 5-phosphate + 2 NADPH + 2 H+ + CO2
The cell needs more NADPH than ribose 5-phosphate:
Glucose 6-phosphate + 12 NADP+ + 7H2O → 12 NADPH + 12 H+ + 6 CO2 + Pi
The cell needs more ribose 5-phosphate than NADPH:
5 Glucose 6-phosphate + ATP → 6 Ribose 5-phosphate + ADP

15. In addition to the pentose pathway, NADPH can be generated by the malic enzyme
+ NADP NADPH + H+ + CO2
Malate is generated in the mitochondria by the TCA (Krebs) cycle.
Erythrocytes which lack mitochondria are thus particularly susceptible to
oxidative damage
Defective glucose 6-phosphate dehydrogenase is the most common enzymatic
defect in humans affecting hundreds of millions of people.
Hemolytic anemia can occur if the individual experience oxidative stress, e.g.
when treated with oxidant drugs or contract a severe infection.