The document discusses the hexose monophosphate shunt (HMP shunt), an alternative pathway to glycolysis. It has three key steps: 1) glucose-6-phosphate is converted to ribulose-5-phosphate, producing NADPH and CO2. 2) ribulose-5-phosphate molecules are rearranged to form fructose-6-phosphate and glyceraldehyde-3-phosphate. 3) this pathway occurs in the cytosol and does not generate ATP. The pathway produces NADPH and pentoses for lipid, nucleotide, and nucleic acid biosynthesis. It is important for red blood cell antioxidant defenses and is regulated by NADPH and insulin. Deficiencies can cause hem

1. HMP SHUNT
DR.J.SIVAKUMAR
ASSOCIATE PROFESSOR

2. INTRODUCTION
• An alternative route for the metabolism of glucose.
• It is the pathway for formation of pentose phosphate. It is also
called hexose monophosphate shunt.

3. Contd..
• It is a multicyclic process in which three molecules of
glucose-6-phosphate give rise to three molecules of CO2
and three molecules of 5-carbon sugars,(ribulose-5-
phosphate).
• The three molecules of ribulose-5-phosphate are arranged
to generate two molecules of fructose-6- phosphate and
one molecule of glyceraldehyde-3- phosphate.
• It does not generate ATP

4. PATHWAY
• SITE : Cytosol
• An irreversible oxidative phase and
reversible nonoxidative phase .
• NADP+ as hydrogen acceptor

5. Contd..
• The pentose phosphate pathway is active in liver,
adipose tissue, adrenal cortex, thyroid,
erythrocytes, testis, and lactating mammary
gland.
• Its activity is low in nonlactating mammary gland
and skeletal muscle.

7. Significance
• The pentoses (ribose-5-phosphate) required for the biosynthesis
of nucleotide and nucleic acids (RNA and DNA) are provided by
pentose phosphate pathway.
• It provides a route for the interconversion of pentoses and
hexoses.
• NADPH is required for the biosynthesis of fatty acids, cholesterol,
steroid hormones and neurotransmitters.
• It is required for oxidation-reduction reactions involved in
detoxification, e.g.for detoxification of drugs by microsomal
cytochrome P450 mono-oxygenase and for reduction of
oxidized glutathione.

8. Contd..
• In RBC, NADPH is required to maintain the level of
reduced glutathione.
• The reduced glutathione protects the RBC membrane
from toxic effect of H2O2 by reducing H2O2 to H2O.

9. Contd..
• NADPH also keeps iron of hemoglobin in reduced ferrous
(Fe2+) state and prevents the formation of
methaemoglobin.
• NADPH is necessary for phagocytosis carried out by white
blood cell.

10. Regulation
• The first step in the pathway, catalyzed by glucose- 6-
phosphate dehydrogenase (G-6-PD) is the rate limiting
step.
• The activity of this enzyme is regulated by cellular
concentration of NADPH. NADPH is a competitive
inhibitor of the enzyme G-6-PD.
• Under well-fed condition, the level of NADPH decreases
and pentose phosphate pathway is stimulated.
• In conditions like starvation and diabetes, the level of
NADPH is high and inhibits the pathway

11. Contd..
• Insulin is also involved in the regulation of pentose
phosphate pathway.
• It enhances the pathway by inducing the enzyme G-6-
PD and 6-phosphogluconolactone dehydrogenase

12. Energetics

13. Clinical importance
• Glucose 6-phosphate dehydrogenase deficiency is X-
linked inherited disorder, characterized by hemolytic
anemia, due to excessive haemolysis
• Most of the patients of G-6-PD deficiency are
asymptomatic and do not show hemolytic anemia under
normal condition.
• However, they develop severe hemolytic anemia when
they are exposed to certain antibiotics, dapsone ,sulpha
drugs ,anti-malarial (primaquine) or antipyretic drugs

14. G-6-PD deficiency and malaria
• The malarial parasite, Plasmodium falciparum infects the
red blood cell, where it depends on the reduced
glutathione and the products of the pentose phosphate
pathway for its optimum growth.
• Therefore, persons with G-6-PD deficiency cannot
support growth of this parasite and thus are less prone to
malaria than the normal person.

16. Wernicke-Korsakoff syndrome
• This is a genetic disorder due to reduced activity of the
TPP-dependent transketolase enzyme. The reduced
activity of transketolase is due to reduced affinity for TPP,
whereas the other TPP dependent enzymes are normal.
• Therefore, in the chronic thiamine deficiency
(Alcoholics)the transketolase enzyme has a much
reduced activity leading to the Wernicke- Korsakoff
syndrome

18. Contd..
• The symptoms of Wernicke-Korsakoff syndrome include
weakness, mental disorder, loss of memory, partial
paralysis, etc.
Treatment
• Thiamine replacement( iv administration)
• Diet and life style modifications

19. Contd..

20. Differences between Glycolysis & HMP shunt

21. Uronic acid pathway
• A pathway in liver for the conversion of glucose to
glucuronic acid, ascorbic acid (except in humans and
other primates as well as in guinea pigs) and pentoses is
referred to as the Uronic acid pathway.
• It is also an alternative oxidative pathway for glucose but
does not generate ATP.

23. Significance
• The uronic acid pathway is a source of UDPglucuronate.
• UDP-glucuronate is a precursor in biosynthesis of
proteoglycans (glycosaminoglycans) and glycoproteins.
• UDP-glucuronate is involved in detoxification reactions
that occur in liver.
• Many naturally occurring waste substances (like bilirubin
and steroid hormones) as well as many drugs (like
morphine, methanol, salicylic acid, etc.) are eliminated
from the body by conjugating with UDP-glucuronate

24. Contd..
• The Uronic acid pathway is a source of UDP-glucose,
which is used for glycogen formation.
• The Uronic acid pathway provides a mechanism by which
dietary D-xylulose can enter the central metabolic pathway.

26. Essential Pentosuria
It is one of the members of the Garrod’s tetrad.
Garrod’s tetrad-albinism,(deficient of tyrosinase),
 alkaptonuria(deficient of Homogentisic di oxygenase)
 cystinuria (genetic disorder) and
 pentosuria
The incidence is 1 in 2,500 births.
It is an inborn error of metabolism.

27. Contd..
• xylitol dehydrogenase and xylulose reductase -Absence of any
of these enzymes leads to pentosuria.
• L-xylulose is excreted in urine and gives a positive Benedict’s
test.
• Barbiturates(anti-depressant drug) aminopyrine(analgesic&
anti-pyretic) etc. will induce Uronic acid pathway and will
increase xylulosuria in such patients.

28. THANK YOU