Last edited: 8/10/2021

1. PENTOSE PHOSPHATE PATHWAY

Pentose Phosphate Pathway: Oxidative & Non-oxidative Phases Medical Editor: Jona Frondoso

OUTLINE Isomerization of DHAP

DHAP is isomerized to the more stable glyceraldehyde-3-
I) INTRODUCTION phosphate (G3P) by triose phosphate isomerase
II) PENTOSE PHOSPHATE PATHWAY
((Figure 2)
III) SIGNIFICANCE OF THE PRODUCTS OF PPP
IV) APPENDIX
V) REVIEW QUESTIONS FYI:
At this point of the glycolytic pathway, we are now dealing
with two molecules of glyceraldehyde 3-phosphate
I) INTRODUCTION (G3P).
Therefore, each succeeding step will result to two
Importance of Pentose Phosphate Pathway (PPP)
molecules of the intermediate or product
o Important in synthesis reactions
 Neurotransmitters
 Lipids (cholesterol) Oxidation of G3P
 Nucleotides
o Free radical reactions Oxidation of glyceraldehyde-3-phosphate to 1,3-
bisphosphoglycerate (1,3-BPG) by glyceraldehyde 3-
phosphate dehydrogenase (Figure 2)
(A) REVIEW OF GLYCOLYSIS o Oxidizing agent is 2 NAD+ which is reduced to 2
Glucose undergoes glycolysis depending on the body’s NADH [Nelson & Cox, 2017]
needs Coupled with the addition of phosphate group to G3P
Location: cytosol forming 1,3-bisphosphoglycerate (1,3-BPG)
GLUT-2
o Transports glucose into the liver cell (Figure 1)
Synthesis of 3-PG producing ATP
Conversion of 1,3-bisphosphoglycerate to 3-
phosphoglycerate (3-PG) with the production of ATP
(Figure 2)
Catalyzed by phosphoglycerate kinase
Shift of the phosphate group from C3 to C2
Shift of phosphate group from carbon 3 to carbon 2 of
phosphoglycerate by phosphoglycerate mutase (Figure
Figure 1. Transport of glucose into the liver cell via GLUT-2 2)
transporter. Produces 2-phosphoglycerate (2PG)
Dehydration of 2-PG
Phosphorylation of Glucose
Dehydration of 2-phosphoglycerate (2PG) by enolase
Addition of phosphate group from ATP to glucose (Figure (Figure 2)
2) Results in the formation of phosphoenolpyruvate (PEP)
Catalyzed by glucokinase
Formation of pyruvate producing ATP
Products are glucose-6-phosphate (G6P) and ADP
Conversion of PEP to pyruvate catalyzed by pyruvate
kinase (Figure 2)
Isomerization of Glucose-6-phosphate
Also produces 2 ATP
Isomerization of glucose 6-phosphate (G6P) to fructose-
6-phosphate (F6P) (Figure 2) FYI:
Catalyzed by phosphoglucoisomerase
ATP from Substrate-Level Phosphorylation (Figure 2)

Phosphorylation of Fructose-6-phosphate Energy Investment Phase = -2 ATP

Addition of phosphate group from ATP to fructose-6-
phosphate (F6P) (Figure 2)
Catalyzed by phosphofructokinase-1 (PFK)
Products are fructose-1,6-bisphosphate (F-1,6BP) and
ADP
-1 ATP from Step 1 (Phosphorylation of glucose)
-1 ATP from Step 3 (Phosphorylation F6P)
Energy Generation Phase = +4 ATP
+2 ATP from Step 7 (Synthesis of 3-PG)
+2 ATP from Step 10 (Formation of pyruvate)

Cleavage of Fructose-1,6-bisphosphate
Net ATP Yield
• Aldolase cleaves fructose 1,6-bisphosphate (F1,6-BP) to
dihydroxyacetone phosphate (DHAP) and glyceraldehyde – 2 ATP + 4 ATP = 2 ATP
3-phosphate (G3P) (Figure 2)

PENTOSE PHOSPHATE PATHWAY METABOLISM: Note #1. 1 of 5

 Formation of 6-Phosphogluconate
Addition of water (H2O) to 6-phosphogluconolactone
producing a proton (H+) and 6-phosphogluconate (Figure
5)
o 6-phosphogluconate - 6-carbon molecule
Catalyzed by lactONase
o Lactase – converts lactose to glucose and galactose

Figure 5. Formation of 6-phosphogluconate from 6-

phosphogluconolactone.

Formation of Ribulose-5-phosphate
Oxidation of 6-phosphogluconate forming ribulose-5-
phosphate (Figure 6)
o Oxidizing agent is NADP+ forming NADPH
o Ribulose-5-phosphate: 5-carbon molecule
Coupled with the decarboxylation of 6-phosphogluconate
producing carbon dioxide (CO2)
Catalyzed by 6-phosphogluconate
o Not as important as G6P dehydrogenase

Figure 2. Overview of the glycolytic pathway and the number of

ATP generated in each step,

II) PENTOSE PHOSPHATE PATHWAY Figure 6. Formation of ribulose-5-phosphate from 6-

Pentose Phosphate Pathway (PPP) and the glycolytic phosphogluconate.
pathway are so intertwined.
Remember:

(A) OXIDATIVE PHASE NADPH Products

Consists of four steps 1st molecule of NADPH
Significance o Oxidation of glucose-6-phosphate
2nd molecule of NADPH
To make NADPH o Formation of ribulose-5-phosphate
To make ribose-5-phosphate

Oxidation of Glucose-6-phosphate Formation of Ribose-5-phosphate and Xyulose-5-

Oxidation of glucose-6-phosphate (G6P) to
phosphogluconolactone (Figure 3)
o G6P - 6-carbon molecule
o Phosphogluconolactone - 6-carbon molecule
Oxidizing agent is NADP+, which picks up hydride ions
(Figure 4), forming NADPH
Catalyzed by glucose-6-phosphate dehydrogenase
Figure 3. Oxidation of glucose-6-phosphate to 6-
phosphogluconolactone.
phosphate
6-
Ribulose-5-phosphate have two fates.
Formation of two different molecules depending on the
enzyme
o Isomerase → Ribose-5-phosphate
o Epimerase → Xyulose-5-phosphate
Formation of ribose-5-phosphate
Isomerization of ribulose-5-phosphate to ribose-5-
phosphate (Figure 7)
o Ribulose-5-phosphate – a ketone
o Ribose-5-phosphate – an aldehyde
Catalyzed by isomerase

Remember: Formation of xyulose-5-phosphate

Hydride has two electrons instead of just 1 electron
Epimerization of ribulose-5-phosphate to xyulose-5-
phosphate (Figure 7)
Catalyzed by epimerase
Figure 4. Chemical structure of hydride

2 of 5 METABOLISM: Note #1. PENTOSE PHOSPHATE PATHWAY

 Fusion of Ribose-5-phosphate and Xyulose-5-
phosphate
Catalyzed by transketolase
o Thiamine pyrophosphate (TPP) - coenzyme of
transketolase
Transketolase catalyzes the transfer of a 2-carbon
fragment from ribose-5-phosphate to xyulose-5-phosphate
Figure 7. Formation of ribose-5-phosphate and xyulose-5-
phosphate from ribulose-5-phosphate. (Figure 8)
o To remember, keep in mind that the chemical structure
of ketone is a carbonyl group in between two carbons,
Remember: so transketolase transfers two carbons.
Isomers vs Epimers Products are:
Isomers o Glyceraldehyde-3-phosphate – 3-carbon molecule
o Same chemical formula but differs in the o Seduheptulose-7-phosphate – 7-carbon molecule
arrangement of their atoms [Nelson & Cox, 2017]
Epimers Fates of Glyceraldehyde-3-phosphate
o A diastereomer which differs in chirality in one
carbon only Can be fed up into the glycolytic pathway
o Ribulose-5-phosphate and xyulose-5-phosphate are o Depends on body’s needs
epimers
o They are identical except for their stereochemistry in Can fuse with Sedoheptulose-7-phosphate
C3
C Ribulose-5- Xyulose-5- Fusion of Glyceraldehyde-3-phosphate and
number phosphate phosphate Sedoheptulose-7-phosphate
3 R R
Catalyzed by transaldolase
4 S R Transaldolase catalyzes the transfer of a 3-carbon
5 S R fragment from sedoheptulose-7-phosphate to
glyceraldehyde-3-phosphate (Figure 8)
R = rotates clockwise; S = rotates counterclockwise
Products are:
o Fructose-6-phosphate – 6-carbon molecule
 Can be fed up into the glycolytic pathway
(B) NON-OXIDATIVE PHASE  Depends on the body’s needs
o Erythrose-4-phosphate – 4-carbon molecule
Carbon-shuffling reactions
Consist of 3 reversible steps (Figure 8)
Significance Fates of Fructose-6-phosphate
Can make ribose-5-phosphate without making Can be fed up into the glycolytic pathway
NADPH via glycolytic intermediates o Depends on body’s needs
 Glyceraldehyde-3-phosphate to make ribose-5-
phosphate Remember:
 Glyceraldehyde-3-phosphate and fructose-6- 5C+ 5C = 3C + 7C = 6C + 4C
phosphate to form erythrose-4-phosphate and
xyulose-5-phosphate Ribose-5- phosphate + Xyulose-5-phosphate →
 Erythrose-4-phosphate and fructose-6-phosphate Glyceraldehyde-3-phosphate + Sedoheptulose-7-
phosphate → Fructose-6-phosphate + Erythrose-4-
to make glyceraldehyde-3-phosphate and
phosphate
sedoheptulose-7-phosphate To remember this reaction, keep in mind that the number
 Glyceraldehyde-3-phosphate and sedoheptulose- of carbons in the reactants is equal to the number carbons
7-phosphate to form ribose-5-phosphate and in the products, which are both 10 (a coincidence in PPP.
xyulose-5-phosphate

Can make ribose-5-phosphate to glycolytic Fusion of Erythrose-4-phosphate and Xyulose-5-

intermediates phosphate
Free ribulose-5-phosphate can be acted on with an
epimerase enzyme forming xyulose-5-phosphate (Figure
8)
Xyulose-5-phosphate reacts with erythrose-4-phosphate
catalyzed by another transketolase enzyme
o TPP – coenzyme of transketolase
Transketolase transfers 2-carbon fragment from xyulose-
5-phosphate to erythrose-4-phosphate (Figure 8)
Products are:
o Glyceraldehyde-3-phosphate
 Can be fed up into the glycolytic pathway
depending on the body’s needs
o Fructose-6-phosphate
 Can also be fed up into the glycolytic pathway
Figure 8. Non-oxidative phase of the pentose phosphate
depending on the body’s needs
pathway.

PENTOSE PHOSPHATE PATHWAY METABOLISM: Note #1. 3 of 5

 III) SIGNIFICANCE OF THE PRODUCTS OF PPP  Deficiency in specific enzymes that generate
NADPH → appearance of Heinz bodies
The two main products of PPP are (indicative of hemolytic anemia)
o NADPH
o Ribose-5-phosphate
(B) RIBOSE-5-PHOSPHATE
Important in biosynthesis of
(A) NADPH
o Nucleotides
A good reducing agent for any type of biosynthetic  DNA
reactions  RNA
Used in o ATP
o Fatty acid synthesis o Electron shuttles
 Specifically, in reduction steps  NAD+
o Cholesterol metabolism  FAD+
 To convert HMG-CoA to mevalonate o Coenzyme A
o Nucleotide metabolism
o Neurotransmitter synthesis
o Free radical reactions
 Aids antioxidants

IV) APPENDIX

Figure 9. Overview of the pentose phosphate pathway (PPP) and the importance of NADPH and ribose-5-phosphate.

4 of 5 METABOLISM: Note #1. PENTOSE PHOSPHATE PATHWAY

 V) REVIEW QUESTIONS

Which of the following statements is correct about the

oxidative phase of the PPP?
a) Begins with the oxidation of glucose-1-phosphate to
6-phosphogluconolactone
b) The phase of the PPP which produces NADH and
ribose-5-phosphate.
c) Isomerase converts ribulose-5-phosphate to ribose-
5-phosphate
d) Xyulose-5-phosphate and ribulose-5-phosphate are
enantiomers.

2) Which of the following statements is correct about

the non-oxidative phase of the PPP?
a) All steps are reversible except to the last step
b) Allows synthesis of ribose-5-phosphate without
making NADPH via glycolytic intermediates
c) Transketolase catalyzes the transfer of a 2-carbon
from xyulose-5-phosphate to ribose-5-phosphate
d) The coenzyme of transaldolase is thiamine
pyrophosphate

3) The first transketolase reaction forms which

intermediate?
a) Sedoheptulose-7-phosphate
b) Fructose-6-phosphate
c) Erythrose-4-phosphate
d) Xyulose-5-phosphate

4) What is the significance of NADPH?

a) To convert HMG-CoA to mevalonate
b) To aid in free radical reactions
c) For neurotransmitter synthesis
d) All of the choices are correct.

5) Which steps involves the production of NADPH?

a) Formation of ribulose-5-phosphate
b) Oxidation of glucose-6-phosphate
c) Formation of 6-phosphogluconate
d) Two of the choices are correct.

CHECK YOUR ANSWERS

VI) REFERENCES
Nelson, D., & Cox, M. (2017). Lehninger Principles of
Biochemistry (7th ed.). New York: W.H Freeman and Company.

PENTOSE PHOSPHATE PATHWAY METABOLISM: Note #1. 5 of 5