Irreversible Oxidative Reactions

The oxidative portion of the pentose phosphate pathway consists of three irreversible reactions that lead to the formation of ribulose 5-phosphate, CO2, and two molecules of NADPH for each molecule of glucose 6-phosphate oxidized (Fig. 1).

This portion of the pathway is particularly important in the liver, lactating mammary glands, and adipose tissue for the NADPH-dependent biosynthesis of fatty acids ; in the testes, ovaries, placenta, and adrenal cortex for the NADPH-dependent biosynthesis of steroid hormones ; and in red blood cells (RBC) for the NADPH-dependent reduction of glutathione .

Figure 1:  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, 8) transketolase (coenzyme: thiamine pyrophosphate), and (7) transaldolase. Δ2C = two carbons are transferred from a ketose donor to an aldose acceptor in transketolase reactions; Δ3C = three carbons are transferred in the transaldolase reaction. This can be represented as: 5C sugar + 5C sugar 7C sugar + 3C
sugar 4C sugar + 6C sugar. NADP(H) = nicotinamide adenine dinucleotide phosphate; = phosphate; CO2 = carbon dioxide.
A. Glucose 6-phosphate dehydrogenation
Glucose 6-phosphate dehydrogenase (G6PD) catalyzes the oxidation of glucose 6-phosphate to 6-phosphogluconolactone as the coenzyme NADP+ gets reduced to NADPH. This initial reaction is the committed, ratelimiting, and regulated step of the pathway. NADPH is a potent competitive inhibitor of G6PD, and the ratio of NADPH/NADP+ is sufficiently high to substantially inhibit the enzyme under most metabolic conditions. However, with increased demand for NADPH, the ratio of NADPH/NADP+ decreases, and flux through the pathway increases in response to the
enhanced activity of G6PD. [Note: Insulin upregulates expression of the gene for G6PD, and flux through the pathway increases in the absorptive state .]
B. Ribulose 5-phosphate formation
6-Phosphogluconolactone is hydrolyzed by 6-phosphogluconolactone hydrolase in the second step. The oxidative decarboxylation of the product, 6-phosphogluconate, is catalyzed by 6-phosphogluconate dehydrogenase. This third irreversible step produces ribulose 5-phosphate (a pentose sugar– phosphate), CO2 (from carbon 1 of glucose), and a second molecule of NADPH (see Fig. 1).

مواضيع ذات صلة

آلية عمل المجموعة الأولى من الهرمونات

الهرمونات وآليات الاستتباب

تدرك (تقويض) الهرمونات وتعطيلها

نقل الهرمونات في البلازما

تغاير خزن الهرمونات وإفرازها

تخليق POMC ومعالجته

The Amino Acids

Absorption & Transport of Transition Metals

Physiologic Roles of The Essential Transition Metals

تخليق الأنجيوتنسين

تخلیق PTH

تخليق الأنسولين