Pentose phosphate pathway

1

• Pentose phosphate pathway
• Alternative path to oxidize glucose
• Active in rapidly dividing cells
• and in cells active in synthesizing
• fatty acids, cholesterol, or steroids
• Electron acceptor is NADP,
• generates NADPH
• NADPH needed for reductive
• biosynthesis
• Products are pentose phosphates
• RNA and DNA precursors
• High amounts of NADPH
• prevent oxidative damage to
• proteins (red blood cells, cornea)
• Nonoxidative phase recycles sugars
• in cells where DNA/RNA are not
• synthesized, to generate more
• NADPH (and CO2).

2
2 equivalents of NADPH are produced per G6P
starting molecule, in dehydrogenase reactions
enzymes are cofactor-specific This is the
oxidative phase oxidations have large negative
free energy change and are essentially
irreversible
intramolecular ester
hydrolysis
Oxidative decarboxylation (C-C bond breakage)

• Note NADPH is used for anabolic
• reductions while NAD is used in
• catabolic oxidations.
• Cells maintain each pool separately
• mainly in the cytoplasm (NADPH)
• and the mitochondria (NAD)

isomerization
3
Non-oxidative (recycling) phase 5C sugars are
converted to 6C sugars Continued recycling
amounts to G6P ? 6 CO2 All reactions are
reversible G6P is regenerated to make more
NADPH Epimerase, transketolase, transaldolase
are unique to pentose phosphate pathway A
related pathway fixes CO2 in plants All enzymes
cytosolic note shared inter- mediates with
glycolysis
glycolytic and gluconeogenic enzymes
4
Transketolase transfer of 2-carbon group
TPP-mediated (mechanism similar to pyruvate
decarboxylase)
5
Transaldolase transfer of 3-carbon
unit Mechanism Schiff base (Lys) stabilization
of carbanion, analogous to aldolase in
glycolysis
6
Mechanistic similarity between transketolase and
transaldolase each must generate and
stabilize a carbanion for C-C bond breakage
and formation
7
Glycolysis, pentose phosphate pathway, and
gluconeogenesis all take place in the
cytoplasm Intermediates are shared Relative
partitioning of metabolites is carried out by
regulating key enzymes
Excess NADPH inhibits the first enzyme in the
oxidative pentose phosphate pathway thus the
G6P is partitioned to glycolysis