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Pentose Phosphate Pathway
Pentose Phosphate Pathway
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PENTOSE-PHOSPHATE PATHWAY
The pathway has two phases: oxidative and non-oxidative phase. The
oxidative phase is a 3-step process that generates 2 NADPH/ carbon oxidized or
CO2 produced. This also produces the five-carbon pentoses that are precursors of
nucleotide synthesis. The non-oxidative phase (produced in cells actively
synthesizing fats) recycles the 5-carbon sugars to synthesize glyceraldehyde-3-
phosphate and/or fructose-6-phosphate.
Oxidative phase:
Reduction of NADP+ (as with NAD+) involves transfer of 2e- plus 1H+ to the
nicotinamide moiety. The reaction is shown below:
Non-oxidative phase
The reactions involve transfer of 2-C (transketolation) and 3-C
(transaldolation) fragments from donors to receivers.
Transketolase and Transaldolase catalyzes these reactions. The donor is usually
a ketose and acceptor is an aldose. D. E. Nicholson has suggested that the names
of these enzymes should be changed, since Transketolase actually transfers an
aldol moiety (glycoaldehyde) and Transaldolase actually transfers a ketol moiety
(dihydroxyacetone). However the traditional enzyme names are used here.
Mechanism:
1. The first transketolation reaction involves transfer of a 2-C fragment from
xylulose-5-phosphate to ribose-5-phosphate. The positively charged N in
the thiazole ring acts as an electron sink, promoting C-C bond cleavage.
The 3-C aldose glyceraldehyde-3-phosphate is released. A 2-C fragment
remains on TPP.
Hexose Monophosphate Shunt 59
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The thiazolium carbanion that results from proton dissociation reacts with the
carbonyl C of xylulose-5-P to form an addition compound.
Overall reaction:
The e-amino group of an active site lysine residue reacts with the carbonyl C of
sedoheptulose-7-phosphate to form a protonated Schiff base intermediate. Aldol
cleavage results in release of erythrose-4-phosphate. The Schiff base stabilizes
the carbanion on C3. Completion of the reaction occurs by reversal, as the
carbanion attacks instead the aldehyde carbon of the 3-carbon aldose
glyceraldehyde-3-phosphate to yield the 6-carbon fructose-6-phosphate.
4. The 3rd step is the second transketolation reaction which transfers 2-C
fragments to the 4-C aldose erythrose-4-phosphate yielding fructose-6-
phosphate and glyceraldehydre-3-phosphate.
5. Glyceraldehyde-3-phosphate can condense with DHAP (isomerization
product of glyceraldehydes-3-phosphate) to form again, fructose-6-
phosphate.
Hexose Monophosphate Shunt 61
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5. Both TPP and lysine (of the transketolase) bind substrate for the reaction.
What effect will this binding have on the substrates of the enzymes?
6. What advantage(s) will the reactions of the non-oxidative phase of the
hexose monosphosphate shunt have in terms of energy utilization?
7. When does the process not proceed to the non-oxidative phase? Explain
briefly.
8. What is/are the function(s) of the pentose phosphate pathway? Explain
briefly.
9. The hexose monophosphate shunt also protects cells such as RBC from
oxidative stress. How? Explain briefly.
References:
1. http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/pentose.htm
2. Mathews, C.K., Van Holde, K.E., and Ahern, K.G. (2000). Biochemistry, 3rd
Ed. San Francisco: Addison-Wesley Publishing Company.
3. Horton, R.H., Moran, L.A., Ochs, R.S., Rawn, J.D. and Scrimgeour, K.G.
(1996) Principles of Biochemistry, 2nd ed. New Jersey: Prentice-Hall
International, Inc.