A Pathway can run in either of two modes B 1

33
Session 20 -
Pentose Phosphate Pathway (PPP)
A. Oxidative Mode: Need NADPH and B. Non-oxidative Mode: Just need pentoses
Roles: Pentoses

1.) Cell's primary source of G G6P F6P GAP P G G6P F6P GAP P
NADPH biosynthetic
reductive cofactor (Malic NADPH
enzyme = another source)
CO2
2.) Source of ribose for
ribonucleotides (also, Pentoses
this is entry portal for Pentoses
metabolism of ribose -- Ribose 5P
from diet) -- Ribulose 5P Carbon scrambling
-- Xyulose 5P network
-- Highly expressed in tissues making lipid To: R5P, Ru5P and X5P (7
-- Expressed in growing tissues (e.g. cancer) Nucleotides and 4 carbon sugars
are also made)

PPP Details (shorthand in 2 pages) -- This is cytosolic pathway C

G G6P
Ribulose-5- P
6-
Lactonase Phosphoglu
PO B -conate DH
PO PO OH PO CO2
H OH OH
O OH O O O
G6POH B
OH OH O H C Ru5P
O O
HO NADP HO HO NADP HO O
H
OH NADPH OH H OH NADPH O OH
next page
+H +H
3 mol β-keto acid

3 CO2
Typically the pathway is
run by processing 3 mol 3 G6P 2 F6P + 1 GAP
of G6P
18 3 carbons 12 3 carbons
carbons carbons
 1
34
PPP (continued)
O CH2OH
CH2OH
CH CH2OH
PO O C O C NH 2
CO2 Ru5P TA
C OH C N
OH C OH Isomerase HO C TA H
TA
C OH CH2OH
CH2OH C OH C OH
CO2 lost HO C OH
O O
from C-1 CH2O P via ene diolate C OH
CH2O P CH
intermediates
Imagine that I have 3 Ru5P(3 mol) C OH
R5P TA C OH TA
molecules of Ru5P
CH2O P
Nucleotides C OH
TK = Transketolase (TPPenz) Ru5P
TA = Transaldolase (works Epimerase S7P CH2O P
like aldolase) Sedoheptulose E4P
TK mechanism 7-Phosphate
CH2OH
CH2OH O
N O C C H
O C
H C TK
HO C HO C C2-TPP + C OH F6P
S
B TPP PO OH
C OH C OH CH2O P
O
CH2O P CH2O P GAP HO

CH2OH OH
X5P (1 mol)
N HO
+
HO C C
S CH2OH
HO C
B O C
C OH TK TK
C2-TPP F6P
CH2O P HO C
O +
C OH O
CH2OH C H
CH2O P C H
HO C TPP + C OH GAP
C OH
Di-hydroxy- CH2O P X5P (1 mol)
ethyl-TPP CH2O P These (3) products are
in mainstream of
C2-TPP GAP GAP Glycolysis / GNG
PPP Shorthand - Helps you see the mass balance A 1
35

F6P Glycolysis
all CO2 come from C-1
GAP GNG
S7P TA DHA-like E4P
C7 1 C3 Fragment 1 + C4 1
3 CO2

G6P Ru5P I R5P TA

C6 3 C5 3 C5 1 F6P F6P
TK C6 1 C6 1
6 NADPH E
C2-TPP
TK C2 1
X5P
C5 1 C2-TPP
GAP C2 1
Everything to this C3 1 *
point is reversible X5P TK GAP
C5 1 C3 1

Summary Points on PPP

1.) Expressed in tissues when making lipid (and in 6.) G6PDH Rate determining step (Oxidative pathway) - stimulated by NADP
growth)
7.) Calvin Cycle = this series of reactions in reverse
2.) If run in oxidative mode, you could oxidize all a.) Photosynthesis Ru1,5BP + CO 2 (2) PGA (2) GAP (Rubisco)
carbons of glucose to CO2 (if use GNG to get
GAP and F6P back to G6P). b.) Must regenerate catalytic molecule of Ru1,5BP (C5 sugar)
c.) Take 6 molecules GAP (18 carbons)
3.) PPP is entry point of dietary ribose into
catabolism GAP * GAP 15 Carbons
Ru1,5BP
C3 6 C3 5 C5 3

GAP (some convert

4.) NADPH helps defend against oxidative stress to F1,6BP)
(cofactor for glutathione reductase) from C3 1
Rubisco If run the carbon scrambling reactions
"Net" Carbohydrate (all reversible) from Right to Left ( ),
5.) Cytosolic pathway synthesis Glycol/GNG this is how plants make
carbohydrates from CO2.
CO2
danger peroxidase reductase Cell regulates generation of NADPH via B
AcCoA NADPH Ru5P sensng need for FA biosynthesis (and
ROOH R'-SH NADP other cytoplasmic NADPH regulated
PPP reactions)
Lipid NADP Glucose
ROH + HOH R'-S-S-R' NADPH + H
= Glu Reductase
harmless G6PDH = RNR
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5.07SC Biological Chemistry I

Fall 2013

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