Oxidative hexose phosphate shunt

The additional pathway diverts glucose 6-phosphate from the first step of glycolysis and reduces NADP" in two redox reactions (Fig. 11-25). This reaction sequence is called the oxidative part of the pathway or the oxidative hexose phosphate shunt. It is especially active in lipogenic cells such as hepatocytes and adipocytes. 

The oxidative pathway for the metabolism of D-glucose 6-phosphate (XLV), distinctive from the glycolytic, Embden-Meyerhof route (see p. 200) and known as the hexose monophosphate shunt, was suggested by certain experiments of Warburg,200 Gerischer,207 Lipmann,208 and Dickens209... 

Pentose phosphate pathway Summary of the path way Reduced coenzymes produced by the pathway PENTOSE PHOSPHATE PATHWAY (p. 143) Also called the hexose monophosphate shunt, or6-phosphogluconate pathway, the pentose phosphate pathway is found in all cells. It consists of two irreversible oxidative reac tions followed by a series of reversible sugar-phosphate interconversions. No ATP is directly consumed or produced in the cycle, and two NADPH are produced for each glu cose 6-phosphate entering the oxidative part of the pathway. 

FMN was first identified as the coenzyme of an enzyme system that catalyzes the oxidation of the reduced nicotinamide coenzyme, NADPH (reduced NADP), to NADP (nicotinamide adenine dinucleotide phosphate). NADP is an essential coenzyme for glucose-6-phosphate dehydrogenase which catalyzes the oxidation of glucose-6-phosphate to 6-phosphogluconrc acid. This reaction initiates the metabolism of glucose by a pathway other than the TCA cycle (citric acid cycle). The alternative route is known as the phosphoglneonate oxidative pathway, or the hexose monophosphate shunt. The first step is ... 

Some mammalian cells have the ability to metabolize glucose 6-phosphate in a pathway that involves the production of C3, C4, C5, C6, and C7 sugars. This process also yields the reduced coenzyme, NADPH, which is oxidized in the biosynthesis of fatty acids and steroids (Chap. 13). Consequently, this metabolic pathway is of major importance in those cells involved in fatty acid and steroid production, such as the liver, lactating mammary gland, adrenal cortex, and adipose tissue. The pentose phosphate pathway, which does not require oxygen and which occurs in the cytoplasm of these cells, has two other names the phosphogluconate pathway (after the first product in the pathway) and the hexose monophosphate shunt (since the end products of the pathway can reenter glycolysis). 

In the previous section we considered three possible pathways for glucose-6-phosphate dephosphorylation by glucose-6-phosphatase, conversion to fructose-6-phosphate followed by oxidation through the Embden-Meyerhof pathway, and conversion to glucose-1-phosphate followed by glycogen synthesis. A fourth pathway exists—the hexose monophosphate shunt [61-63]. 

A number of intermediates common to both the hexose monophosphate shunt and the glycolytic pathway are glucose-6-phosphate, fructose-6-phosphate, fructose-6,1-diphosphate, and triose phosphate. Thus, the two pathways can be expected to compete for intermediates, and, indeed, when a reconstituted glycolytic system made of purified enzymes is added to the reconstituted hexose monophosphate shunt, glucose oxidation by the shunt is inhibited by glycolysis. 

Glucose must be converted to glucose-6-phosphate for further metabolic transformation. Glucose-6-phos-phate may then be used for glycogen synthesis or oxidized through glycolysis, the hexose monophosphate shunt, and the glucuronic pathway. 

The various reactions of the hexose monophosphate shunt have been summarized in Fig. 9. By this pathway it is possible to oxidize completely glucose 6-phosphate without having to go through the BMP pathway or the tricarboxylic acid cycle. A more detailed account of this oxidative path-... 

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