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PENTOSE PHOSPHATE
PATHWAY
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PENTOSE PHOSPHATE PATHWAY
Function:
To supply reducing equivalents for biosynthesis
(NADPH) and pentoses for DNA and RNA biosynthesis.
Location:
Everywhere.
Connections: To glycolysis and glycogen through glucose 6-phosphate.
Shares some enzymes with glycolysis.
To DNA-RNA synthesis through ribose 5-phosphate.
Regulation:
NADPH inhibits.
NADP activates.
High glucose 6-phosphate activates.
EQUATIONS:
Making NADPH:
3 Glucose 6-P 6NADP ¡
2 fructose 6-P glyceraldehyde 3-P 3CO2 6NADPH 6H
Making ribose 5-P:
Glucose 6-P 2NADP ¡
ribose 5-P CO2 2NADPH 2H
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BG McGraw-Hill: Gilbert, Basic Concepts in Biochemistry, JN 5036
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Basic Concepts in Biochemistry
The hexose monophosphate pathway has several names just to confuse you. It’s called the hexose monophosphate shunt or pathway (HMP
shunt or pathway), or the pentose phosphate pathway, or the phosphogluconate pathway (Fig. 15-1). The pathway in its full form is complicated and has complicated stoichiometry. Usually it’s not necessary to
remember all of it. The important points are that it makes NADPH for
biosynthesis and riboses (C-5 sugars) for DNA and RNA synthesis.
NADPH is a reducing agent that is reserved for biosynthetic pathways—notably fatty acid synthesis. Thus, the HMP pathway is called
upon when reducing equivalents and fatty acid synthesis are turned on.
Primarily, the regulation of the pathway is through the supply and
demand of NADPH.
NADPH is also used to keep the cellular (and mitochondrial) glutathione in the reduced form through the action of glutathione reductase:1
GSSG NADPH H ¡ 2GSH NADP
glycogen
NADPH
gluconolactone
6-phosphogluconate
CO2
glucose-6-P
*
NADPH
ribulose-5
phosphate
(C5)
glucose
glucose-6-P
dehydrogenase
glycolosis
gluconeogenesis
ribose-5-P
4, 5, 6, & 7
carbon sugars
transketolase
(thiamin)
transaldolase
Figure 15-1 The Pentose Phosphate Pathway
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Glutathione (GSH) is a tripeptide, -glutamylcysteinylglycine. The -glutamyl part means
that the amino group of the cysteine is attached to the side chain carboxyl group of the glutamic acid rather than to the -carboxyl. GSH is a thiol (sulfhydryl)-containing molecule that
can be oxidized to the disulfide, GSSG, by cellular oxidants such as hydrogen peroxide. It
helps protect cells against damage that can be caused by oxidants.
BG McGraw-Hill: Gilbert, Basic Concepts in Biochemistry, JN 5036
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Pentose Phosphate Pathway
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This reaction also protects proteins with cysteine residues from becoming oxidized to the disulfide since the GSH can be used to reduce the
protein disulfide back to the thiol form:
Protein—SS—Protein 2GSH ∆ 2 protein—SH GSSG
A somewhat more trivial thing to remember about the HMP pathway is that this is one of the places you’ve seen the vitamin thiamin
pyrophosphate. This cofactor is necessary for the transketolase reaction
that is in the middle of the HMP pathway. The transketolase reaction converts two C-5 sugars to a C-7 and a C-3. The other place you’ve seen
thiamin pyrophosphate as a cofactor is in the pyruvate dehydrogenase
and -ketoglutarate dehydrogenase reactions.
BG McGraw-Hill: Gilbert, Basic Concepts in Biochemistry, JN 5036