section 15.3
Alternative Pathways of Glucose Metabolism and Hexose Interconversions
301
6 Ribulose 5-P (30)
Epimerase /
Isomeras©
4 Xylulose 5-P (20)
2 Ribose 5-P (10)
F I G U R E 1 5 -2 0
Nonoxidative phase of the pentose phosphate pathway. Numbers in
parentheses show the distribution of carbon atoms between the various
branches of each reaction. TK = transketolase; GAP = glyceraldehyde
3-phosphate; DHAP = dihydroxyacetone phosphate; P = phosphate.
3. Transfer of a two-carbon unit from a 2-keto sugar to
the carbonyl carbon (Ci) of an aldose by a
transketolase, which requires thiamine pyrophosphate
and magnesium as cofactors. A covalent enzyme-
substrate intermediate is formed similar to the one
that occurs during the pyruvate dehydrogenase
reaction (Chapter 13).
4. Transfer of carbons 1-3 from a ketose phosphate to
the carbonyl carbon (Ci) of an aldose phosphate by a
transaldolase. The reaction mechanism is similar to
that of aldolase, with formation of a Schiff base
intermediate involving the £-amino group of a lysyl
side chain on the enzyme.
Glutamate + Cysteine •
N A D P*
NADPH + H -
A T P
A D P +P
W
Mg
y
-Glutamylcysteine
A T P -
-G lycine
adp + f;-^
— y-Glutamylcysteinylglycine (G SH )
RO O H or H jO ,-
RO H or H * 0-
—
Oxidized glutathione (G SSG )
From pentose phosphate pathway
F I G U R E 1 5 -2 1
Metabolism of glutathione. (1) y-Glutamylcysteine synthase; (2) GSH
synthase; (3) glutathione peroxidase (Se-containing enzyme); 4.
glutathione reductase (an FAD enzyme).
reduce glutathione for protection against oxidant injury.
Glutathione (y-glutamylcysteinylglycine; GSH) is syn-
thesized by
y
-glutamylcysteine synthase and GSH syn-
thase (Figure 15-21). In the steady state, 99.8% of the
glutathione is in the reduced form (GSH), and only 0.2%
is in the oxidized form (GSSG), because of theNADPH-
dependent reduction of oxidized glutathione, catalyzed by
glutathione reductase:
y -G lu ta m y lc y s te in y lg ly c in e
I
S
I
s
y -G lu ta m y lc y s te in y lg ly c in e
(G S S G )
NADPH + H
NADP
S H
2 y -G lu ta m y lc y s te in y lg ly c in e
(G S H )
Glutathione reductase also catalyzes reduction of mixed
disulfides of glutathione and proteins (Pr):
The flexibility of this phase of the pathway allows for
interconversion of a number of sugars and glycolytic in-
termediates, in part because of the ready reversibility of
the reactions and regulation of the enzymes by substrate
availability. Thus, the pathway adjusts the concentrations
of a number of sugars rather than act as a unidirectional
anabolic or catabolic route for carbohydrates.
Pentose Phosphate Pathway in Red Blood Cells
In the erythrocyte, glycolysis, the pentose phosphate
pathway, and the metabolism of 2,3-bisphosphoglycerate
(Chapter 28) are the predominant pathways of carbohy-
drate metabolism. Glycolysis supplies ATP for membrane
ion pumps and NADH for reoxidation of methemoglobin.
The pentose phosphate pathway supplies NADPH to
Pr-S-SG + NADPH + H+ ^ Pr-SH + GSH + NADP+
Thus,
the
active
sulfhydryl
groups
of hexokinase,
glyceraldehyde-phosphate dehydrogenase, glutathione re-
ductase, and hemoglobin (-SH group at the /1-93 position)
are maintained in the reduced form. Glutathione reductase
is an FAD enzyme composed of two identical subunits
encoded by a single locus on the short arm of human
chromosome 8.
GSH is used in the inactivation of potentially dam-
aging organic peroxides (e.g., a peroxidized unsaturated
fatty acid) and of hydrogen peroxide. Hydrogen perox-
ide is formed through the action of superoxide dismutase
(Chapter 14):
20j + 2H+
H20 2 + 0 2
