Monophosphate shunt

Cells require a constant supply of N/ X)PH for reductive reactions vital to biosynthetic purposes. Much of this requirement is met by a glucose-based metabolic sequence variously called the pentose phosphate pathway, the hexose monophosphate shunt, or the phosphogluconate pathway. In addition to providing N/VDPH for biosynthetic processes, this pathway produces ribos 5-phosphate, which is essential for nucleic acid synthesis. Several metabolites of the pentose phosphate pathway can also be shuttled into glycolysis. 

Superoxide is produced by the NADPH oxidoreduc-tase (oxidase), which is a membrane-bound enzyme complex containing a flavoprotein that catalyses the transfer of single electrons from NADPH in the cytosol to extracellular oxygen. NADPH is mainly supplied by the hexose monophosphate shunt. In resting cells, the oxidase complex is inactive and disassembled, but is rapidly reconstituted and activated by chemotactic mechanisms or phagocytosis (Baggiolini and Thelen, 1991). 

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... 

The hexose monophosphate pathway has several names just to confuse you. It s called the hexose monophosphate shunt or pathway (HMP shunt or pathway), or the pentose phosphate pathway, or the phospho-gluconate pathway (Fig. 15-1). The pathway in its full form is complicated and has complicated stoichiometry. Usually it s not necessary to remember all of it. The important points are that it makes NADPH for biosynthesis and riboses (C-5 sugars) for DNA and RNA synthesis. 

A series of investigations were performed in search of alterations in enzyme activities of the hexose monophosphate shunt in tissues of various tumors (H13, K17, R8), and an increase of the activities of enzymes involved was found. 

W16. Willmer, J. S., The influence of adrenalectomy upon the activity of the hexose monophosphate shunt in the livers and mammary glands of lactating rats. Can. J. Biochem. and Physiol. 38, 1265-1273 (1960). 

C5a and C5a des Arg stimulate aerobic glycolysis, hexose monophosphate shunt activity, glucose uptake and the respiratory burst of human neutrophils. All of these processes are stimulated in neutrophil suspensions incubated in the absence of cytochalasin B, but the responses are considerably enhanced if this inhibitor of microtubule assembly is present. Stimulated rates of oxidative metabolism are maximal within 2 min of addition of peptides, with half-maximal responses obtained at 30-60 nM C5a and 1-3 pM C5a des Arg. 

Figure 5.3. The glutathione cycle. Abbreviations HMP, hexose monophosphate shunt GSH, reduced glutathione GSSH, oxidised glutathione GR, glutathione reductase GPO, glutathione peroxidase. In the system shown, H2O2 is converted into H20, but the system is also effective in breaking down organic peroxides.

L. M. McIntyre, D. R. Thorburn, W. A. Bubb, and P. W. Kuchel, Comparison of computer simulations of the f type and 1 type non oxidative hexose monophosphate shunts with 3IP... 

Pentose phosphate pathway (= hexose monophosphate shunt) generation of NADPH G6PDH deficiency... 

Nasr et failed to observe a change in the ratio of NADPH to NADP in the tracheal epithelium of rats exposed to ozone at 33 ppm for an hour. This apparently negative in vivo finding is not surprising, inasmuch as NADP will be rapidly reduced back to NADPH if ozone does not disrupt the structural integrity of pyridine nucleotides. In addition, de novo thesis of pyridine nucleotides may also occur. The intracellular ratio of reduced to oxidized pyridine nucleotides is under tine cellular control, in that the oxidation of NADPH or NADH results in the stimulation of enzymatic activity, which restores the initial ratio. In the case of NADPH, its oxidation increases the activity of the hexose monophosphate shunt this also occurs after the oxidation of glutathione. The rel-... 

A, The pentose phosphate pathway (PPP), also called the hexose monophosphate shunt, is an alternate pathway of glucose metabolism that supplies the NAD PH required by many biosynthetic pathways. 

Thiamine pyrophosphate is a coenzyme and the active form of vitamin B. It functions as coenzyme in decarboxylation of a-keto acid and in hexose monophosphate shunt. 

The actions of non-steroidal anti-inflammatory drugs appear to be diverse. Phenylbutazone and sulfmpyrzone inhibited several effects of FMLP on PMNs increased adhesiveness, stimulation of the hexosemonophosphate shunt, lysosomal enzyme release, and formation of O These effects were explained by the ability of both phenylbutazone and sulfinpyrazone to inhibit binding of labelled FMLP to PMNs. Both were selective in that neither inhibited responses of PMNs to Csa and neither inhibited the stimulation of the hexose monophosphate shunt by latex or by opsonized Candida. The responses of PMNs to FMLP, including the release of O have also been inhibited by 5,8,11,14 eicosatetraynoic acid, an inhibitor of the metabolism of arachidonic acid h by indomethacin and by... 

Lipid peroxidation will oxidize GSH, and the reduction of this oxidized glutathione (GSSG), catalyzed by GSH reductase, will also use NADPH and hence contribute to the depletion of this nucleotide (Fig. 7.41). The hexose monophosphate shunt will be stimulated to... 

The result is redox cycling, which produces active oxygen species, which can deplete NADPH and GSH and potentially cause peroxidation of membrane lipids. NADPH is generated by the hexose monophosphate shunt, and NADP can also be reduced by GSH (Fig. 6.18). 

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