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Query: UMLS:C0027960 (mole)
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The glucose transport system in Leishmania tropica promastigotes was characterized by the use of labeled 2-deoxy-D-glucose (2-DOG), a nonmetabolizable glucose analog. The uptake system has a Q10 of 2 and a heat of activation of 10.2 kcal/mole. The glucose transport system is subject to competitive inhibition by 2-DOG, glucosamine, N-acetyl glucosamine, mannose, galactose, and fructose which suggests that substitutions in the hexose chain at carbons 2 and 4 do not affect carrier specificity. In contrast, changes at carbon 1 (alpha-methyl-D-glucoside, 1,5-anhydroglucitol) and carbon 3 (3-0-methyl glucose) lead to loss of carrier affinity since these sugars do not compete for the glucose carrier. Sugars that compete with the glucose carrier have one common feature--they all exist in the pyranose form in solution. The carrier for D-glucose does not interact with L-glucose or any of the pentose sugars tested. Uptake of 2-DOG is inhibited by glycerol. This inhibition, however, is noncompetitive; it is evident; therefore, that glucose and glycerol do not compete for the same carrier. Glycerol does not repress the glucose carrier since cells grown in presence of glycerol transport the sugar normally.
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PMID:Specificity of the glucose transport system in Leishmania tropica promastigotes. 97 53

3-mercaptopicolinic acid (3MP) was shown to be a powerful and specific inhibitor of the phosphoenolpyruvate carboxykinase (PEP-carboxykinase; ATP:oxyloacetate carboxylyase (transphosphorylating), EC 4.1.1.49) isolated and purified to homogeneity from Trypanosoma (Schizotrypanum) cruzi epimastigotes (Urbina, J. A., 1987, Arch. Biochem. Biophys. 258, 186-195). In the presence of saturating concentrations of the cosubstrates the inhibition was purely noncompetitive toward all substrates in the carboxylation reaction. The inhibition was specific to this enzyme, being nonexistent or moderate toward eight other enzymes tested that are involved in glycolysis, hexose monophosphate shunt, Krebs' cycle, and amino acid metabolism. These facts, together with the kinetic constants of the enzyme and the intracellular concentrations of its substrates, predicted a very potent inhibition of the reaction catalyzed by this enzyme in vivo. In accordance of this prediction 200 microM 3MP inhibited 2.2-fold the production of [2,2'-13C]succinate from D-[1-13C]glucose by intact epimastigotes under anaerobic conditions, as shown by 13C NMR and 1H NMR spectroscopy; correspondingly the overall glucose consumption rate decreased by the same factor, while the relative rate of production (per mole of glucose consumed) of the other main product of glucose catabolism, [3-13C]alanine, was increased 3-fold by the drug. Under aerobic conditions the glucose catabolism was faster (negative Pasteur effect) and the drug at the same concentration again blocked succinate production but had negligible effects on glucose consumption. On the other hand, 200 microM 3MP blocked completely the epimastigotes' catabolism of L-[U-14C]proline through the Kreb's cycle via PEP-carboxykinase, as indicated by the disappearance of 14C label present in alanine, pyruvate, citrate, and isocitrate after 1 h of incubation in the presence of the labeled amino acid, while the amount of radioactivity present in alpha-ketoglutarate and malate doubled. The results support the proposition that PEP-carboxykinase has a central role in the energy metabolism of this organism as it is essential for the catabolism of amino acids.
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PMID:Inhibition of phosphoenolpyruvate carboxykinase from Trypanosoma (Schizotrypanum) cruzi epimastigotes by 3-mercaptopicolinic acid: in vitro and in vivo studies. 222 21

Fatty acid-binding protein (FABP) was isolated, purified, and characterized from developing human fetal lung cytosol by gel filtration and ion-exchange chromatography. FABP exists in three immunochemically identical forms, DE-I, DE-II, and DE-III, having Mr 15,200 +/- 200 each and isoelectric pH 7.8, 6.9, and 5.4, respectively. DE-I is almost lipid-free, DE-II binds mainly long-chain unsaturated fatty acids, and DE-III is an arachidonic acid carrier. One mole of DE-II and DE-III each binds 1 mol of fatty acids noncovalently. Concentrations of all these FABPs increase gradually from early gestation to term. Defatted lung FABP reverses the inhibitory effect of palmitoyl coenzyme A (CoA) (PAL-CoA) on lung glucose-6-phosphate dehydrogenase (G6PD), a key enzyme of the hexose monophosphate (HMP) shunt pathway. This protein when added alone activates the enzyme, suggesting that the original submaximal activity is probably due to the presence of endogenous long-chain fatty acyl CoA esters in the cytosols. As FABP is present in relatively high concentration in most mammalian cells, the potent inhibitory effects of long-chain acyl CoA esters on the HMP shunt pathway in vitro are not seen in intact cells.
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PMID:Purification and characterization of fatty acid-binding proteins from human fetal lung. 276 6

Glycated albumin levels showed a progressive increase during normal pregnancy. The mean values (mole hexose/mole protein) were 1.68 +/- 0.27 (n = 15) in nonpregnant women, 1.83 +/- 0.21 (n = 11) in first trimester, 2.00 +/- 0.41 (n = 13) in second trimester, and 2.42 +/- 0.49 (n = 15) in third trimester. Glycated hemoglobin levels indicated a biphase pattern with low values at midpregnancy (controls 0.29 +/- 0.05, first trimester 0.30 +/- 0.04, second trimester 0.27 +/- 0.05, and third trimester 0.33 +/- 0.04). The data suggest that glycated albumin reflects the decreased glucose tolerance in pregnancy better that glycated hemoglobin levels. The reasons for the differing pattern of the two glycated proteins are discussed.
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PMID:Glycated albumin and glycated hemoglobin levels in normal pregnancy. 335 15

The effects of gossypol on membrane structure and membrane-associated functions were studied to explore possible reasons for the ability of gossypol to disrupt cellular processes, many of which involve intracellular and plasma membranes. The experiments reported here measured the effects of gossypol on membrane order, permeability, and hexose transport. Electron spin resonance (ESR) studies of I(12,3) nitroxide fatty acid spin-labeled unilamellar liposomes showed that exposure to 0.05 to 4 mM gossypol caused a dose-dependent increase in the polarity-corrected order parameter (S), indicating reduced motional freedom of the spin probe after exposure to gossypol. This observation is consistent with the idea that gossypol causes an ordering or "condensing" of the membrane lipid matrix. Gossypol-induced changes in order parameter in phosphatidylcholine:cholesterol liposomes varied depending on the liposome composition. Liposomes exposed to gossypol also showed increasing permeability to glycerol as the gossypol:phospholipid ratio increased up to 10 mole %. Higher concentrations of gossypol were less effective at enhancing permeability. In addition, basal and insulin-stimulated 2-deoxy-D-[3H]glucose transport were inhibited in freshly isolated rat adipocytes incubated with gossypol at 37 degrees. Half-maximal inhibition occurred at approximately 0.2 mM for uptake in both the presence and absence of 40 ng/ml insulin. Microscopic observation of the cells under low power (40 X) confirmed that diminished hexose transport was not simply due to breakage of the adipocyte plasma membrane, resulting in a decrease in intact cell population and decreased accumulation of label in the gossypol-treated cells. Gossypol produced no significant changes in numbers of intact cells or gross morphology at the concentrations tested. We suggest that ordering and increased permeability of the lipid regions of plasma and subcellular membranes may contribute to some of the toxic and pharmacologic properties of gossypol. Our results also support the idea that gossypol may exert more pronounced effects in cells that are most sensitive to variations in availability of glucose substrates for energy metabolism.
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PMID:Membrane structural/functional perturbations induced by gossypol. Effects on membrane order, liposome permeability, and insulin-sensitive hexose transport. 353 79

Metalloproteinase from the venom of Bothrops asper (proteinase G) is a glycoprotein with 1% neutral hexose and 3.5 moles of sialic acid per mole of protein. It hydrolyses a number of protein substrates such as casein, hemoglobin, gelatin and fibrinogen, whose alpha chain is degraded preferentially. The pH optimum of hydrolysis of casein is approximately 9.5. The protease is devoid of hemorraghic, esterolytic and amidolytic activities. The proteolytic activity of the enzyme increases by about 20% in the presence of 0.2 mM Ca2+ and Mg2+. Among the other ions tested, only Cd2+ and Fe2+ markedly decreased its activity. EDTA and cysteine are also strong inhibitors. In the presence of Ca2+ and EDTA, Zn2+ ions restored 50% of the activity. The amino acid composition shows fewer acidic residues than in related proteinases from other snake venoms.
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PMID:Characterization of a metallo-proteinase from Bothrops asper (terciopelo) snake venom. 367 44

The growth yields of Escherichia coli on glucose, lactose, galactose, maltose, maltotriose, and maltohexaose were estimated under anaerobic conditions in the absence of electron acceptors. The yields on these substrates exhibited significant differences when measured in carbon-limited chemostats at similar growth rates and compared in terms of grams (dry weight) of cells produced per mole of hexose utilized. Maltohexaose was the most efficiently utilized substrate, and galactose was the least efficiently utilized under these conditions. All these sugars were known to be metabolized to glucose 6-phosphate and produced the same pattern of fermentation products. The differences in growth yields were ascribed to differences in energy costs for transport and phosphorylation of these sugars. A formalized treatment of these factors in determining growth yields was established and used to obtain values for the cost of transport and hence the energy-coupling stoichiometries for the transport of substrates via proton symport and binding-protein-dependent mechanisms in vivo. By this approach, the proton-lactose stoichiometry was found to be 1.1 to 1.8 H+ per lactose, equivalent to approximately 0.5 ATP used per lactose transported. The cost of transporting maltose via a binding-protein-dependent mechanism was considerably higher, being over 1 to 1.2 ATP per maltose or maltodextrin transported. The formalized treatment also permitted estimation of the net ATP yield from the metabolism of these sugars; it was calculated that the growth yield data were consistent with the production of 2.8 to 3.2 ATP in the metabolism of glucose 6-phosphate to fermentation products.
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PMID:Influence of transport energization on the growth yield of Escherichia coli. 392 98

The serum transferrin from the primate, Macaca fascicularis is isolated by a purification protocol consisting of ammonium sulphate precipitation and column chromatography. The hexose (galactose + mannose) content of Macaca transferrin is 4.7 mole per mole of protein. Quantitative determination of the sialic acid content shows that there are two sialic acid residues per molecule of Macaca transferrin. This conclusion is supported by the neuraminidase treatment of Macaca transferrin, in which there is a 2-step decrease in electrophoretic mobility. Monoferric Macaca transferrins with Fe3+ selectively labelled at the C- and N-terminal sites (TfFec and FeNTf) are prepared at pH 5.5 and 8.5 using ferric dinitrilotriacetate [Fe(NTA)2] chelate and ferrous ammonium sulphate, respectively.
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PMID:Primate (Macaca fascicularis) transferrin: isolation and partial characterization. 405 69

1. The effect of chlorpromazine on hexose transfer across the human erythrocyte membrane was investigated by optical and isotopic techniques in intact erythrocytes.2. Chlorpromazine produces two phases of inhibition of glucose exit at 17 degrees C in both types of experiment.3. Glucose exchange flux shows a much smaller decrease in flux rate at the same concentrations of chlorpromazine at 17 degrees C.4. Sorbose and glucose entry at 36 degrees C show a similarly complex inhibition by chlorpromazine. The inhibitor constant (K(i)) for these effects with the two sugars is similar.5. An Arrhenius plot shows that the average energy change for the reaction of the carrier with chlorpromazine is -46 kJ mole(-1) and suggests that a drug-induced conformational change in the carrier may occur.6. These findings require models of hexose permeation to contain separate terms in their kinetics for net and exchange fluxes and the predictions of one such model have been compared with the experimental results.
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PMID:Further effects of chlorpromazine on the hexose permeability of the human erythrocyte. 475 82

1. The cyst wall of Colpoda steinii has been isolated and its chemical nature examined. It had a nitrogen content 13.9+/-0.2% (s.d.) and an ash 8.6+/-1.6% (s.d.). After lipid and hot-acid extraction there was a variable residual phosphorus of 0.19-0.64%. The protein nature, indicated by infrared and ultraviolet absorption, was confirmed when 100mug. of hydrolysed wall gave a ninhydrin colour equivalent to that given by 0.88-1.01mumoles of glycine. Hexosamine, hexose, pentose, lipid and dipicolinic acid were absent. 2. Paper chromatography of hydrolysates, besides showing the presence of the usual protein amino acids and three unidentified ninhydrin-reacting spots, indicated the presence of large amounts of glutamic acid. Estimated by chromatography, the amount present was 52.9+/-0.6 (s.d.) g./100g. of ash-free wall; manometric estimation of l-glutamic acid with l-glutamate 1-carboxy-lyase gave 46.5+/-0.9 (s.d.) g./100g. 3. Free carboxyl groups were estimated by titration as 0.159+/-0.011 (s.d.) mole/100g. and those present as amide as 0.154+/-0.004 (s.d.) mole/100g., and the total was compared with the dicarboxylic acid content 0.360+/-0.010 (s.d.) mole/100g. 4. After treatment with 98% formic acid 25-30% of the wall material could be extracted by 0.05m-sodium carbonate solution (extract 1); after treatment of the residue with performic acid a further 62-63% based on the original weight could be extracted by 0.05m-sodium carbonate (extract 2). 5. The average values found for the glutamic acid contents were 21.7g./100g. for extract 1 and 58.0g./100g. for extract 2. The cysteic acid content of whole oxidized wall was about 5.8g./100g. and of extract 2 also about 5.8g./100g. The glutamic acid and cysteic acid contents of the final residue were also investigated. 6. The significance of these extraction experiments in relation to the wall structure is discussed.
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PMID:The cyst wall of Colpoda steinii. A substance rich in glutamic acid residues. 495 13


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