Hexose monophosphates

Fig. 3. Biosynthetic pathways for amino acids. HMP = hexose monophosphate pathway CAC = citric acid cycle P = phosphate PP = pyrophosphate ...

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. 

Acceptable answers to part 1) indude amino adds and fatty adds or specific examples of each, such as glycine or stearic add respectively. The obvious answer for part 2) is the central metabolite pyruvate, though all of the adds of the TCA cycle would be appropriate. Answers to part 3) include the prindpal add of the hexose monophosphate... 

False. D-gluconolactone is produced directly from glucose via glucose oxidase. 6-phosphogluconolactone is an intermediate in the hexose monophosphate pathway. 

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). 

Defects in the Hexose Monophosphate Pathway and Glutathione Metabolism... 

Mature red blood cells do not have nuclei, mitochondria, or microsomes therefore red blood cell function is supported through the most primitive and universal pathway. Glucose, the main metabolic substrate of red blood cells, is metabolized via two major pathways the Embden-Meyerhof glycolytic pathway and the hex-ose monophosphate pathway (Fig. 1). Under normal circumstances, about 90% of the glucose entering the red blood cell is metabolized by the glycolytic pathway and 10% by the hexose monophosphate pathway. 

The most important product of the hexose monophosphate pathway is reduced nicotinamide-adenine dinucleotide phosphate (NADPH). Another important function of this pathway is to provide ribose for nucleic acid synthesis. In the red blood cell, NADPH is a major reducing agent and serves as a cofactor in the reduction of oxidized glutathione, thereby protecting the cell against oxidative attack. In the syndromes associated with dysfunction of the hexose monophosphate pathway and glutathione metabolism and synthesis, oxidative denaturation of hemoglobin is the major contributor to the hemolytic process. 

Deficiencies of enzymes involved in glycolysis, the hexose monophosphate pathway, the closely related glutathione metabolism and synthesis, and nucleotide metabolism have emerged as causes of hereditary nonspherocytic hemolytic anemias (Table 1) (F10, Fll, M27). Some enzyme deficiencies, such as diphospho-glycerate mutase deficiency, lactate dehydrogenase deficiency, and NADH cy-... 

Triose phosphate isomerase (TPI) catalyzes the interconversion of glyceralde-hyde-3-phosphate and dihydoxyacetone phosphate and has an important role in glycolysis, gluconeogenesis, fatty acid synthesis, and the hexose monophosphate pathway. Red blood cell TPI activity measured in vitro is approximately 1000 times that of Hx, the least active glycolytic enzyme. TPI is a dimer of identical subunits, each of molecular weight 27,000, and does not utilize cofactors or metal ions. Posttranslational modification of one or both subunits may occur by deamidination, resulting in multiple forms of the enzymes and creating a complex multibanded pattern on electrophoresis. 

Glutathione reductase (GR) catalyzes the reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH) using NADPH provided from the hexose monophosphate pathway. GR, a ubiquitous flavoenzyme, maintains a high value of two for the GSH/GSSG ratio in the red blood cells. l,3-Bis(2-chloroethyl)-nitrosourea (BCNU) selectively inhibits cellular GR. GR is composed of two identical subunits, each of molecular mass 50 kDa (S8). The three-dimensional structure and mechanism of catalysis have been established for human GR (K17). 

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. 

Under basal conditions 5% of brain glucose is metabolized via the pentose phosphate shunt (PPS), also termed the hexose monophosphate pathway [66], a pathway active in both neurons and astrocytes. The PPS has... 

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... 

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