The hexose monophosphate pathway (HMP), also known as the pentose phosphate pathway, is an alternative to glycolysis focused on the production of NADPH and pentoses which are vital for biosynthetic processes including fatty acid and nucleotide synthesis. It consists of an oxidative phase that generates NADPH and a non-oxidative phase that interconverts sugar phosphates, producing intermediates for glycolysis and nucleotide synthesis. The pathway is crucial for cells lacking mitochondria, providing reducing power and addressing oxidative stress, particularly in erythrocytes.

1. METABOLISM
PREPARED BY ;
BULBUL SHRESTHA
PUSHPA MAHATO
YOGITA GURUNG

3. HEXOSE MONOPHOSPHATE PATHWAY
 Hexose monophosphate pathway or HMP Shunt is also called as pentose phosphate
pathway(PPP) or phosphogluconate pathway.
This is an alternative pathway to Glycolysis and TCA cycle for the oxidation of
glucose.
 However , HMP pathway is more anabolic in nature , since it is concered with the
biosynthesis of NADPH and Pentoses .
BIOLOGICAL SIGNIFICANCE;
A) Importance of NADPH
 It is used in the biosynthesis of fatty acids and steroids
 It is used in the synthesis of certain amino acids
 It keeps the glutathione of RBC in reduced state to preserve the integrity of RBC
membrane
 The process phagocytosis requires NADPH
 It is required for the detoxification of drugs

4. B) Importance of pentoses
 The pentose and its derivatives are used for the synthesis of nucleic acids ( DNA ,RNA )
and many mucleotides such as (ATP ,NAD+ ,FAD , CoA)
HMP Pathway – a unique multifunctional pathway
 The pathway starts with Glucose-6 phosphate .
No ATP is directly utilized or produced in HMP Pathway .
 It is a unique multifunctional pathway , since there are several interconvertible substances
produced which may proceed in different directions in metabolic reactions
LOCATION;
 It takes place in the cytoplasm of both prokaryotes and eukaryotes
 The tissues suchas liver , adipose tissue , adrenal gland ,erythocytes, testes,and lactating
mammary gland are highly active in HMP shunt.

5. How does it happens?
The breakdown of the simple sugar, glucose, in glycolysis provides the first 6-carbon
molecule required for the pentose phosphate pathway. During the first step of glycolysis,
glucose is transformed by the addition of a phosphate group, generating glucose-6-phosphate,
another 6-carbon molecule. The pentose phosphate pathway can use any available molecules
of glucose-6-phosphate, whether they are produced by glycolysis or other methods.
Now, we are ready to enter the first of two phases of the pentose
phosphate pathway:
1) The oxidative phase
2) The non-oxidative phase

7. 1.The oxidative phase
First four reactions are irreversible and oxidative in which glucose molecule is
oxidized twice generating two molecules of NADPH and glucose is converted into Ribose-5
phosphate.

8. REACTION 1ST : CONVERSION OF GLUCOSE TO GLUCOSE -6 PHOSPHATE
 This reaction is catalyzed by the enzyme
hexokinase and a molecule of ATP is utilized .
This is a primary step of glycolysis.
REACTION 2nd : CONVERSION OF GLUCOSE 6-PHOSPHATE TO 6-PHOSPHOGLUCONOLACTONATE
 This reaction is catalyzed by an enzyme
glucose6 -phosphate dehydrogenase (G6PD)
 In this reaction a molecule of NADPH
is produced

9. REACTION 3rd : CONVERSION OF 6-PHOSPHOGLUCONOLACTONE TO
6-PHOSPHOGLUCONATE
 This reaction is hydrolysis reaction
catalyzed by hydrolase enzyme i.e 6-phospho gluconolactonase
REACTION 4th :CONVERSION OF 6-PHOSPHOGLUCONATE
TO RIBOSE- 6 -PHOSPHATE
 This reaction is catalyzed by the enzyme 6-phosphogluconate dehydrogenase to produce
3-keto 6 phosphogluconate which undergoes decarboxylation to produce ribulose
phosphate
 In this reaction a molecule of NADPH is generated.

10. Reactants Products Enzyme Description
Glucose 6-phosphate +
NADP+
→ 6-phosphoglucono-δ-
lactone + NADPH
glucose 6-phosphate
dehydrogenase
Dehydrogenation. The
hydroxyl on carbon 1 of
glucose 6-phosphate turns
into a carbonyl, generating a
lactone, and, in the
process, NADPH is
generated.
6-phosphoglucono-δ-
lactone + H2O
→ 6-phosphogluconate + H+ 6-phosphogluconolactonase Hydrolysis
6-phosphogluconate +
NADP+
→ ribulose 5-
phosphate + NADPH + CO2
6-phosphogluconate
dehydrogenase
Oxidative decarboxylation.
NADP+ is the electron
acceptor, generating another
molecule of NADPH, a CO2,
and ribulose 5-phosphate.
The entire set of oxidative reactions can be summarized as follows:

13. THE NON OXIDATIVE PHASE
 Non-Oxidative reactions is followed by a series reversible sugar phosphate inter-conversion reaction.
 REACTION 5th ;
Ribulose-5-phosphate is epimerized to produce xylulose 5-phosphate in the presence of enzyme
phosphor pentose epimerase. Similarly ribulose-5-phosphate is also keto-isomerized into ribose 5-
phosphate.
 REACTION 6th ;
Xylulose-5-phosphate transfer two carbon moiety to ribose 5-phospahate in the presence of enzyme
transketolase to form sedoheptulose-7-phosphate and glyceraldehyde 3—phosphate.
 REACTION 7th ;
Sedoheptulose -7-phosphate transfer three carbon moiety to glyceraldehyde -3-phosphate to
form fructose 6-phopsphate and erythrose 4-phosphate in the presence of enzyme transaldolase.

14.  REACTION 8th;
Transketolase enzyme catalyse the transfer of two carbon moiety from Xylulose-5-phosphate to
erythrose-4- phosphate to form fructose-6-phosphate and glyceraldehyde-3-phosphate.
 REACTION 9th ;
Fructose-6-phosphate and glyceraldehyde-3-phosphate is later enter into glycolysis and kreb’s cycle.
 The rate and direction of reversible reaction depends upon the needs of cell.
 If cell needs only NADPH then fructose-phosphate and glyceraldehyde-3-phosphate are converted
back to glucose by reverse glycolysis, otherwise converted to pyruvate and enter TCA cycle
generating ATPs.

15. Reactants Products Enzymes
ribulose 5-phosphate → ribose 5-phosphate Ribose-5-phosphate isomerase
ribulose 5-phosphate → xylulose 5-phosphate Ribulose 5-Phosphate 3-Epimerase
xylulose 5-phosphate + ribose 5-
phosphate
→ glyceraldehyde 3-
phosphate + sedoheptulose 7-
phosphate
transketolase
sedoheptulose 7-
phosphate + glyceraldehyde 3-
phosphate
→ erythrose 4-phosphate + fructose
transaldolase
xylulose 5-phosphate + erythrose
→ glyceraldehyde 3-
phosphate + fructose 6-phosphate
transketolase
The entire set of non oxidative reactions can be summarized as follows:

17. RESULTS OF PENTOSE PHOSPHATE PATHWAY
• Oxidative portion : Irreversible
Generates two NADPH , which can then be used in fatty acid synthesis and cholestrol
synthesis and for maintaining reduced glutathione inside RBCs
• Nonoxidative portion : Reversible
Generates intermediate molecules ( Ribose-5 -phosphate ; Glyceraldehyde-3-phosphate;
fructose-6-phosphate) for nucleotide synthesis and glycolysis

18. SIGIFICANCE OF PENTOSE PHOSPHATE PATHWAY
HMP is only the cytoplasmic pathway that generates NADPH
 NADPH is produced in this pathway acts as reducing agent during biosynthesis of
various molecules eg. fattyacids.
This pathway generates 3, 4, 5, 6 and 7 carbon compounds which are precursors for
biosynthesis of other molecules. Eg nucleotides are synthesized from ribose-5-phsophate.
 Pentose phosphate pathway is very essential for cell lacking mitochondria (eg.RBCs) for
generation of NADPH.
Triose, tetrose, pentose, hexose and heptose sugar are generated as intermediate products
in pentose phosphate pathway.
NADPH is also used to reduce (detoxify) Hydrogen peroxide in cell.
Resistance to malaria in some Africans are associated with deficiency of glucose-6-
phosphate dehydrogenase enzyme because malarial parasites depend upon HMP shunt to
reduce glutathione in RBCs.

19. REFERENCES
BIOCHEMISTRY 3rd Edition Dr. U . Satayanarayan & Dr . U. Chakrapani
Slideshare; Pentose phosphate pathway by Mr. Anup Muni Bajracharya