Hexose monophosphate shunt activity

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. 

Both these compounds can also cause methemoglobin formation, stimulation of hexose monophosphate shunt activity in isolated suspensions of red cells, and reduced cell viability. 

Martens, M. E. (1994). Hexose monophosphate shunt activity in human epidermal keratinocytes exposed to sulfur mustard. In Proceedings of the Meeting of Research Study Group-3 on Prophylaxis and Therapy Against Chemical Agents (NATO Technical Proceedings AC/243(Panel 8)TP/9, pp. 6.1-6.4). Brussels, Belgium NATO. 

Atamna, H., Pascarmona, G., and Ginsburg, H. (1994). Hexose-monophosphate shunt activity inb Plasmodium falciparum-infected erythrocytes and free parasites. Mol. Biochem. Parasitol. 67, 79-89. 

Cooper, M. R., McCall, C. E., and DeChatelet, L. R. Stimulation of leukocyte hexose monophosphate shunt activity by ascorbic acid. 

Kaplan and Basford (1976) in their study of neutrophil function in four patients with megloblastic anemia showed that resting levels of hexose monophosphate shunt activities were slightly lower in PMN leukocytes from patients with vitamin Bi2 deficiency. However, when challenged with the latex beads or staphylococci, HMPS activity was only 1/3 that of controls. There was no impairment in leukocytes from patients with folic acid deficiency. Microbicidal activity was also slightly decreased in... 

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). 

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). 

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-... 

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 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). 

Fig. 1. Integrated scheme showing the metabolic systems of regulation operating in eu-ryhaline Crustacea (after ref. 9). Broken lines indicate an inhibitory action of the effector and the heavy lines indicate activation. Notice the key role played by glutamic dehydrogenase as well as the controls exerted on the reactions utilizing reducing equivalents. The cAMP concentration is higher in concentrated medium than in dilute medium. The hormone responsible for this effect is not yet identified. HMPS, hexoses monophosphate shunt.

Pyruvate dehydrogenase, especially in the adipose tissue, is stimulated by a high insulin/glucagon ratio. This leads to the production of acetyl-CoA, which may enter the Krebs cycle in the fed state. The more likely possibility is the biosynthesis of fatty acids from acetyl-CoA. The latter requires NADPH, and for this reason, the hexose monophosphate shunt is also activated. 

Studies at the U.S. Army Medical Research Institute of Chemical Defense are thus far consistent with the proposal that, with the exception of activation of hexose monophosphate shunt (Martens, 1994), this biochemical cascade may contribute to blister formation. In addition, however, the process would appear to require an active inflammatory response and altered fluid dynamics in the affected tissue to generate the very large blisters seen after sulfur mustard exposure. 

Schnyder, J., Bagglionoi, M. (1980). Induction of plasminogen activator secretion in macrophages by electrochemical stimulation of the hexose monophosphate shunt by methylene blue. Proceedings of the National Academy of Science (USA), 77, 414-417. 

---