
Pentose phosphate pathway
o An alternative path for glucose 6 phosphate
o Key generator for NADPH
 Fatty acid biosynthesis
 Drug detox
 Glutathione system
o Overall reaction
 3 glucose-6-P + 6 NADP+  3 CO2 + 6 NADPH + 6 H+ + 2 fuctose-6-P
+ glyceraldehyde-3-P
o 2 phases
 Oxidative phase consists of three reactions where NADPH is formed by
three irreversible oxidation reactions converting glucose 6-P to a
ketopentose + CO2
 Glucose 6-P is oxidized, NADP+ is reduced: Rate-limiting step for
the pathway (G-6-P dehydrogenase)
 Important! The 1st and 3rd steps are inhibited by NADPH: cell
doesn’t want to run this pathway if NADPH levels are sufficient.
 The reactions of Phase 1 are irreversible…only occur if NADP+ is
available


Non-oxidative phase consists of 5 freely reversible reactions that
produces ribose 5-P and glycolysis / gluconeogenesis intermediates
 5 rearrangement and transfer reactions that occurs in 2 parts: freely
reversible
 Main point is this…source of Ribose-5-P for nucleotide
synthesis – or reactions can lead back to glycolysis
intermediates fructose-6-phosphate and glyceraldehyde-3phosphate.
 The reactions of Phase 2 are all reversible…these can function
independently to meet metabolic needs for ribose 5-P or for
glucose metabolism intermediates.
When NADPH levels are normal, Phase 1 is shut down, but step 2 can
operate as needed.

NADPH uses
o NADPH is used by phagocytic cells:
 NADPH oxidase uses NADPH to form super oxide from O2 in the
mechanism for killing micoroganisms taken up by phagocytic cells.
o NADPH is central player in the defense against reactive oxygen species,
especially in red blood cells.
 NADPH helps to maintain glutathione in an active form.
 Glutathione peroxidase : 2GSH + ROOH  GSSG + ROH +
H2O
 Glutathione reductase : GSSG + NADPH + H+  2GSH +
NADP+


Pentose phosphate generates NADPH, which is needed in cellular
defenses against ROS. NADPH supplies reducing power to glutathione
reductase (3) to regenerate reduced GSH. If there is a glucose-6phosphate dehydrogenase deficiency, the cell will not have the needed
NADPH, and oxidized glutathione (GSSG) will build up. Without
reduced GSH, glutathione will not have the reducing power to destroy
H2O2.
Interconversion of Sugars
o There are eight carbohydrates that are considered to be very important.
 Mannose, galactose, glucose, fucose, xylose, N-acetylneuraminic acid, Nacetylglucosamine and N-acetylgalactosamine
o Fructose and galactose come from (review structures)
 sucrose (fructose-glucose disaccharide)
 lactose (galactose-glucose disaccharide)
o fructose and galactose are transported into cells and phosphorylated on carbon
1, similar to glucose
o Fructose
 Fructose is metabolized mainly in the liver
 Key point for disease: Aldolase B
 Aldolase B defect: causes accumulation of F-1-P, which is bad
 These patients need to avoid fructose!
 Hexokinase phosphorylates glucose preferentially, but will work on
fructose
 fructose can also be produced from glucose:
 glucose is reduced to sorbitol, which reduces the aldehyde group to
an alcohol
 sorbitol is oxidized at C-2 to form fructose
 Sperm cells use fructose as energy source while in seminal fluid, then
glucose when in the female reproductive tract.
o Galactose
 Net result: galactose is converted to a glucose metabolism intermediate
 Through use of UDP to activate molecule so epimerase can act in
interconversio between galactose and glucose
 UDP-galactose and UDP-glucose are used in the synthesis of
glycoproteins, glycolipids and proteoglycans
 UDP-galactose is also used to form the milk sugar lactose in the mammary
gland.
 Glucuronides
 First step is the production of UDP-glucuronate (oxidation of
UDP-glucose)
 Next is the transfer of the glucuronate moiety onto another
compound (“R”), which can be a protein, another sugar, etc.
 The glucuronate moiety is then modified to a final form, such as
the GAGs, amino sugars, etc.
 Glucuronides are added to compounds to make them water
soluble (important in conjugation step of detox system)
 Deficiency
 Non-classical galactosemia: Galactokinase is deficient and
galactose can’t be processed.
o Can be released back in to blood and processed by kidneys
for excretion
 Classical galactosemia: can’t form UDP-galactose or make
molecules dependent on UDP-galactose
o Galactose-1-P accumulates in liver. Bad for liver cells.