Hexose Monophosphate Shunt Glycolysis

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. 

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. 

Alternatively, it is possible to write a sequence of reactions, including the action of phosphofructokinase and aldolase on seven-carbon intermediates, in which the carbon of ribulose-5-phosphate is converted mainly to glyceralde-hyde-3-phosphate. Such a pathway, with the triose phosphate entering the glycolytic sequence, amounts to a bypass, or shunt, around the first reactions of glycolysis, and the name hexose monophosphate shunt is sometimes used. Any amount of ribose-5-phosphate or erythrose-4-phosphate that may be needed for biosynthetic sequences can also be ob-... 

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). 

Now, let fatty acid biosynthesis starting from glucose. For that look at the integration of the various pathways involved Glycolysis, hexose monophosphate shunt, Pyruvate-malate shuttle, and Fatty acid biosynthesis. It requires reducing equivalents, redox balance and provision of required cytosolic ATP s as well as carbon source. 

The two major metabolic pathways necessary for normal RBC metabolism are the hexose monophosphate shunt pathway, with its associated enzyme systems, and the Embden-Myerhof pathway of anaerobic glycolysis. The former is responsible primarily for maintaining Hgb in the rednced state and thns preventing the formation of methemoglobin, while the latter metabolizes glucose to lactic acid, which leads to adenosine triphosphate formation. 

PRP depletes cells of NAD+ at vesicating doses of sulphur mustard, leading to the inhibition of glycolysis, stimulation of the NADP-dependent, hexose monophosphate shunt and cell death (Papirmeister et al., 1984,1985). Stimulation of this latter enzyme pathway has also been associated with enhancement of protease synthesis and release, resulting in localized subepidermal blister formation in the skin (Smulson, 1989). 

The pentose phosphate pathway is also called the hexose monophosphate shunt (HMP shunt). It shunts hexoses from glycolysis, forming pentoses, which may be reconverted to glycolytic intermediates. 

A number of studies on the metabolism of 3FG and 4FG in Locusta miaratoria have been undertaken. Both 3FG and 4FG are toxic to locust with LD50 s of 4.8 mg/g and 0.6 mg/g respectively. In vitro studies showed that 3FG is metabolized in the fat body, via the NADP-linked aldose reductase, to 3-deoxy-3-fluoro-D-glucitol (3FGL). This metabolite was detected in the hemolymph of the insect and shown to be both a competitive inhibitor and a substrate for NAD-linked sorbitol dehydrogenase, thereby generating 3-deoxy-3-fluoro-D-fructose (3FF) (541. Subsequently, it was shown by in vivo radio-respirometric analysis of C02 and appropriate chase experiments, that 3FG metabolism irreversibly inhibits glycolysis and not the hexose monophosphate shunt or tricarboxylic acid cycle (55). In addition, the release of fluoride ion and H20 from D-[3- H]-3FG was also observed. Based on the mechanism of aldolase (55) and triosephosphate isomerase... 

Glucose is an important source of energy and building blocks. In mammalian tissue, it is degraded essentially in four metabolic pathways glycolysis, the hexose monophosphate shunt, the tricarboxylic acid cycle, and the uronic cycle. 

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. 

The egg and the embryonic cell are well endowed with bioenergetic pathways. The multiple-enzyme systems involved in glycolysis, the hexose monophosphate shunt, the Krebs cycle, the electron transport chain, and oxidative phosphorylation have all been found in the vertebrate embryo. In the embryonic and in the mature cell, oxidation through the Krebs cycle, electron transport, and coupling of oxidation and phosphorylation occur in mitochondria. The chemical energy provided by these pathways is needed for normal development because if either glycolysis, Krebs cycle, or electron transport chain inhibitors are administered in vivo or added to explanted chick or sea urchin embryos, embryonic development is arrested. 

The postnatal development of alkaline phosphatase in the intestinal mucosa of rats and mice is similar to that of tryptophan pyrrolase. Much work in mammalian developmental biochemistry was done on developing liver. Studies on prenatal liver include investigations on the bioenergetic pathways and studies of the formation of enzyme found exclusively in liver. Burch [13] measured the activity of several enzymes involved in glycolysis, the hexose monophosphate shunt, glycogenolysis, and gluconeogenesis. The results of these studies show that the biochemical development of the liver can be divided into three periods prenatal, from 0 to 21 days, and after 21 days. 

Pyruvic decarboxylase controls the entry of the end products of glycolysis into the Krebs cycle. Therefore, thiamine deficiency must have dramatic consequences if no alternative pathway is available for pyruvic acid oxidation. Understandably, in the absence of an alternative pathway, thiamine deficiency leads to a block of pyruvic decarboxylation, which is the first of the two reactions of the Krebs cycle requiring thiamine. In addition, half of the thiamine content of the brain is used in that reaction. The maintenance of the integrity of the Krebs cycle is probably more important to the cell than that of the hexose monophosphate shunt. 

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. 

In considering the effect of insulin or diabetes on carbohydrate metabolism of muscle preparation in vitro, the effect of insulin on the conversion of glucose to CO2 and the fate of the various possible pathways for glucose—glycolysis, the tricarboxylic acid cycle, the hexose monophosphate shunt, and glycogen synthesis—will be examined separately. 

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