One fate of G6P is the
pentose pathway.
Pentose Phosphate Pathway
Also known as:
• Pentose shunt
• Hexose monophosphate shunt
• Phosphogluconate pathway
• It occurs in the cytosol.
The pentose pathway is a shunt.
• The pathway begins with the glycolytic intermediate glucose 6-P.
• It reconnects with glycolysis because two of the end products of the
pentose pathway are glyceraldehyde 3-P and fructose 6-P; two
intermediates further down in the glycolytic pathway.
• It is for this reason that the pentose pathway is often referred to as a
shunt.
Moderate glucose flux
Glycolysis
only
Large glucose flux
Pentose
Phosphate
Glycolysis Pathway
Importance of pentose phosphate pathway :
Generation of NADPH
• mainly used forreductive
synthesis of fatty acids,
cholesterol and steroid
hormones.
• hydroxylation reaction in
metabolism of phenylalanine and
tryptophan.
• production of reduced
glutathione in erythrocytes and
other cells.
Production of ribose residues
- used for nucleotide, nucleic acid ,
and coenzyme (NAD/NADP, FAD
CoA) biosynthesis
Serves as an entry into Glycolysis
NADPH is a
phosphorylated
form of NADH.
• NADH is usually used to drive the phosphorylation
of ADP to ATP.
• NADPH is used where reducing potential is
required for synthetic reactions.
Glutathione is a
tripeptide composed of
glutamate, cysteine,
glycine.
Reduced glutathione
(GSH) maintains the
normal reduced state
of the cell.
Reduced
glutathione (GSH)
Glutathione Functions -1
• It serves as a reductant.
• Conjugates to drugs making them water
soluble.
• Involved in amino acid transport across
cell membranes.
• Cofactor in some enzymatic reactions.
– rearrangement of protein disulfide
bonds.
Glutathione Functions -2
• The sulfhydryl of GSH is used to
reduce peroxides (ROS) formed
during oxygen transport.
– Reactive oxygen species (ROS)
damage macromolecules (DNA,
RNA, and protein) and ultimately
lead to cell death.
• The resulting oxidized form of GSH is
two molecules linked by a disulfide
bridge (GSSG).
• The enzyme glutathione reductase
uses NADPH as a cofactor to reduce
GSSG back to two moles of GSH.
Thus, the pentose pathway is linked
to the supply of adequate amounts
of GSH.
Glutathione redox cycle: NADPH and
Glutathione protect the cells against oxidative
damage
HMP pathway very important in RBCs which are very prone to oxidative
damage
Glutathione and Erythrocytes -2
• The reduced form of glutathione serves as a
sulfhydryl buffer.
• It maintains cysteine residues in hemoglobin
and other proteins in a reduced state.
• GSH is essential for normal RBC structure and
keeping hemoglobin in Fe++ state.
The pentose
pathway can be
divided into two
phases.
Non-oxidative
interconversion of
sugars
Regulatory enzyme
5 carbon atoms
Step 1 and step 3 are
irreversible with large
standard free energy change
Oxidative phase of PPP
• This is the end of HMP pathway for many tissues
• while in the others the pathway continues towards the
non-oxidative phase. NADPH and ribose 5-phosphate
are the end products formed in this phase which play
their respective roles further.
• Overall reaction of oxidative phase of PPP
Glucose 6-phosphate + 2 NADP+ +H2
O
ribose 5-phosphate +CO2
+
2N
A
DP
H
+
2
H+
Nonoxidative phase of HMP shunt
• In tissues which primarily require NADPH, pentose
phosphates are recycled into G 6-P.
• Step 1: Epimerisation of ribulose 5-phosphate to xylulose 5-P
Nonoxidative reactions of HMP pathway
• Transketolase requires the coenzyme thiamine pyrophosphate (TPP),
the transaldolase does not.
• Ingested ribose can enter the glycolytic pathway through the pentose
pathway.
• All reactions are reversible
Thy are the link back to
glycolysis
Transketolase
Transaldolase : transfer of 3C fragment
Fate of triose sugars
• Glycolysis, PPP and gluconeogenesis are
interconnected through shared intermediates.
• GL3-P is converted to DHAP and they can join
together by aldolase as in gluconeogenesis to form
Fructose1,6 bisphosphate
• Triose phosphates can be oxidized by glycolysis to
pyruvate.
• Fate of triose determined by cells relative needs for
pentose phosphates, NADPH and ATP
HMP pathway
• The reactions of the non-oxidative portion of
the pentose pathway are readily reversible.
• The concentrations of the products and
reactants can shift depending on the
metabolic needs of a particular cell or tissue.
Rapidly dividing cells require more ribose 5-
phosphate than NADPH.
The need for NADPH and ribose 5-
phosphate is balanced.
More NADPH is needed than ribose 5-phosphate; Fatty
acid synthesis in adipose cells.
The cell needs both NADPH and ATP
Conditions for hemolytic anemia related
G6PD deficiency.
• The ingestion of oxidative agents that
generate peroxides or reactive oxygen
species (ROS).
– Antimalarials - pamaquine
– purine glycoside from fava beans.
• Individules with G6PD deficiency can not
produce sufficient GSH to cope with the ROS.
• Proteins become cross linked leading to
Heinz body formation and cell lysis.
Glucose 6-phosphate DH deficiency and
nonspherocytic hemolytic anemia.
• Over 300 genetic variants of the G6PD protein
are known.
• Thus, there is a remarkable variation in the
clinical spectrum.
• G6PD deficiency is an inheritable X-linked
recessive disorder.
• Approximately 10-14% of the male African
American population is affected.
• It is also seen in Caucasians from the
Mediterranean Basin.
• People with the disorder are not normally anemic and
display no evidence of the disease until the red cells
are exposed to an oxidant or stress.
Drugs that can precipitate this reaction:
• antimalarial agents
• sulfonamides (antibiotic)
• aspirin
• nonsteroidal antiinflammatory drugs (NSAIDs)
• nitrofurantoin
• quinidine
• quinine
• exposure to certain chemicals - mothballs
FAVISM
• Individuals with G6PD deficiency must not eat
Fava beans.
• Pythagoras
• Erythrocytes lyse=dark or black urine.
• Interesting
– The growth Plasmodium falciparum
(malaria parasite) fails in G6PD deficient
individuals.
Wernicke Korsakoff syndrome
• Severe deficiency of thiamine, a component of TPP
• More common in alcoholics as alcohol lowers the absorption of
thiamine
• Can be exacerbated by mutation in transketolase; low affinity
for thiamine.
• Slowing down of PPP
• Severe memory loss, mental confusion and paralysis
