The oxidative portion of the pentose phosphate pathway consists of three reactions that lead to the formation of ribulose 5-phosphate, CO2, and two molecules of NADPH for each molecule of glucose 6-phosphate oxidized.
IRREVERSIBLE OXIDATIVE REACTIONS
The oxidative portion
of the pentose phosphate pathway consists of three reactions that lead to the
formation of ribulose 5-phosphate, CO2, and two molecules of NADPH
for each molecule of glucose 6-phosphate oxidized (Figure 13.2). This portion
of the pathway is particularly important in the liver, lactating mammary
glands, and adipose tissue, which are active in the NADPH-dependent
biosynthesis of fatty acids; in the testes, ovaries, placenta, and adrenal
cortex, which are active in the NADPH-dependent biosynthesis of steroid
hormones; and in red blood cells (RBCs), which require NADPH to keep
glutathione reduced.
Glucose 6-phosphate
dehydrogenase (G6PD) catalyzes an irreversible oxidation of glucose 6-phosphate
to 6-phosphogluconolactone in a reaction that is specific for oxidized NADP
(NADP+) as the coenzyme. The pentose phosphate pathway is regulated primarily
at the G6PD reaction. NADPH is a potent competitive inhibitor of the enzyme,
and, under most metabolic conditions, the ratio of NADPH/NADP+ is sufficiently
high to substantially inhibit enzyme activity. However, with increased demand
for NADPH, the ratio of NADPH/NADP+ decreases, and flux through the cycle
increases in response to the enhanced activity of G6PD. Insulin upregulates
expression of the gene for G6PD, and flux through the pathway increases in the
absorptive state.
6-Phosphogluconolactone
is hydrolyzed by 6-phosphogluconolactone hydrolase. The reaction is
irreversible and not rate limiting. The oxidative decarboxylation of the
product, 6-phosphogluconate, is catalyzed by 6-phosphogluconate dehydrogenase.
This irreversible reaction produces a pentose sugar–phosphate (ribulose
5-phosphate), CO2 (from carbon 1 of glucose), and a second molecule
of NADPH (see Figure 13.2).
Figure 13.2 Reactions of the
pentose phosphate pathway. Enzymes numbered above are: 1, 2) glucose
6-phosphate dehydrogenase and 6-phosphogluconolactone hydrolase,3)
6-phosphogluconate dehydrogenase, 4) ribose 5-phosphate isomerase, 5)
phosphopentose epimerase, 6 and 8) transketolase (coenzyme: thiamine pyrophosphate),
and 7) transaldolase. Δ2C
= two carbons are transferred in transketolase reactions; Δ2C = three carbons are transferred in
the transaldolase reaction. This can be represented as: 5C sugar Δ2C,
+ 5C sugar 7C sugar + 3C sugar Δ2C, 4C sugar + 6C
sugar. NADP(H) = nicotinamide adenine dinucleotide phosphate; P = phosphate.
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