Pentose Phosphate Shunt

Hexose Monophosphate Shunt

(HMP Shunt)

HMP Shunt

• HMP is a minor oxidation pathway for glucose

• It is an alternative pathway which involves

phospho–pentoses as intermediates for

purposes other than energy production

HMP Shunt

• HMP occurs in the Cytoplasm of:

1. Liver

2. Lactating mammary gland

3. Adipose tissue

4. Red blood cells

5. Adrenal cortex

Rate

limiting

enzymeOxidation

Oxidative Decarboxylation

Hexose Monophosphate Shunt

• The first step:

Hexose Monophosphate Shunt

• Reactions of the hexose monophosphate

pathways:

• Enzymes numbered above are

1. Glucose 6-phosphate dehydroganase

and gluconolactone hydrolyase

2. 6-phosphogluconate dehydrogenase

3. Phosphopentose isomerase

4. Phosphopentose epimerase

5. Transketolase (TPP cofactor)

6. Transaldolase

7. Transketolase (TPP cofactor)

TPP

TPP

TPP

3 molecules

3rd 2nd 1st

2 molecules

1 molecule

Regulation of HMP Shunt

1. Insulin increases the activity of HMP pathway

by stimulating the synthesis of

dehydrogenases involved in HMP pathway

2. Galactose-1-phosphate inhibits G-6-P DH

Metabolic Significance of HMP Shunt

1) It is the only source of phosphorylated

pentoses which used for the synthesis of:

A. Nucleotides: ATP & GTP

B. Coenzymes: FMN, FAD, NAD+

C. Certain vitamins: B2 & B12

D. Nucleic acids: DNA & RNA

Metabolic Significance of HMP Shunt

2) It is the major source of NADPH+ which is essential for:

A. Fatty acid synthesis for lipogenesis which occurs in

liver, adipose tissue & lactating mammary gland

B. Steroid synthesis (Adrenal cortical hormones, Sex

hormones) which is active in adrenal cortex, testes,

ovaries & placenta

C. Act as coenzyme of glutathione reductase which keeps

GSH in reduced state

Other NADPH+ Source

• Malic enzyme (In the cytoplasm) catalyze the oxidative

decarboxylation of malate to pyruvate and CO2, with the

concomitant reduction of the cofactor NADP+ to NADPH

• Malate + NADP+ pyruvate + CO2 + NADPHMalic enz.

Metabolic Significance of HMP Shunt

3) NADPH is essential for keeping the reduced form of

glutathione (G-SH), which is essential for keeping the red

blood cell wall intact, since G-SH is essential for:

A. Keeping iron of Hb in Ferrous state (Fe2+)

B. Keeping globin of Hb in native structure

C. Preventing accumulation of free radicals & H2O2 in RBCs

So Keeping RBCs wall intact preventing hemolysis

Glutathione Protects us from Oxidation

1 2 3

Protects RBC's against hemolysis4

Reduced GlutathioneOxidized Glutathione

Rate limiting enzyme

Favism or Primaquine Sensitivity

Fava beans)

Aspirin)

Metabolite (Like, Oxidation H2O2Sulfa Drugs)

Primaquine)

H2O2 + 2 G-SH Glutathione Peroxidase 2 H2O + G-S-S-G

G-S-S-G + NADPH Glutathione Reductase 2 G-SH + NADP+

Glucose-6-phosphate + NADP+ Glucose-6-P DH

NADPH + 6-phospho

gluconolactone

Fava Beans

Child with

Favism

With signs of

anemia(decreased red

blood cell count,

jaundice, etc.)

– Favism is a significant disease in society today

– it plays a role similar to sickle cell anemia

– It may act as a defense mechanism against malaria

– The unusually high number of oxidants in the blood can

kill the malaria, bacteria, Plasmodium falciparum

– Interestingly, the highest incidence of this disease is

found in areas where malaria is present (Mediterranean

and African areas)

Conclusion

Glucuronic Acid Synthesis

HMP Shunt

• Glucuronic acid is used in:

1. Synthesis of Proteoglycans

(Glycosaminoglycans, GAGs)

2. Excretion of Bilirubin and Steroid compounds

(Glucuronidation)

3. Detoxification of certain drugs and their

metabolites by increasing their solubility

(Glucuronidation)

Metabolic Significance of Glucuronic Acid

Malic EnzymesOfficial Names of

• Malate dehydrogenase (decarboxylating)

• Malic enzyme

• NADP-Malic enzyme

• Pyruvic-Malic carboxylase

• Malate + NADP+ pyruvate +

CO2 + NADPH

Malic enz