Synthase overproduction

Berger SH, Jenh CH, Johnson LF et al. Thymidylate synthase overproduction and gene amplification in fluorodeoxyuri-dine-resistant human cells. Mol Pharmacol 1985 28 461—467. 

Overproduction of the chromosomal genes for the dihydrofolate reductase (DHFR) and the dihydroptero-ate synthase (DHPS) leads to a decreased susceptibility to trimethoprim and sulfamethoxazol, respectively. This is thought to be the effect of titrating out the antibiotics. However, clinically significant resistance is always associated with amino acid changes within the target enzymes leading to a decreased affinity of the antibiotics. 

Unsold lA, LiSM, Overproduction, purification and characterization of FgaPT2, a dimethylallyltryptophan synthase from Aspergillus fumigatus, Microbiology... 

E) Structural changes in dihydropteroate synthase and overproduction of PABA. 

Mammalian cells (and some bacteria) lack the enzymes required for folate synthesis from PABA and depend on exogenous sources of folate therefore, they are not susceptible to sulfonamides. Sulfonamide resistance may occur as a result of mutations that (1) cause overproduction of PABA, (2) cause production of a folic acid-synthesizing enzyme that has low affinity for sulfonamides, or (3) impair permeability to the sulfonamide. Dihydropteroate synthase with low sulfonamide affinity is often encoded on a plasmid that is transmissible and can disseminate rapidly and widely. Sulfonamide-resistant dihydropteroate synthase mutants also can emerge under selective pressure. 

Furthermore, as already mentioned above, the interaction of superoxide with NO synthase in vascular tissue may lead to uncoupling of this enzyme and increasing superoxide production [117]. Therefore, the overproduction of superoxide may affect superoxide/nitric oxide by different ways, resulting in cell injury. It is interesting that some biomolecules may be useful for improving this balance. Thus, 17(3-estradiol upregulated NO synthase expression and inhibited NADPH oxidase expression in human endothelial cells [136]. 

HC Gramajo, J White, CR Hutchinson, MJ Bibb. Overproduction and localization of components of the polyketide synthase of Streptomyces glaucescens involved in the production ofthe antibiotic tetracenomycin C. JBacteriol 173 6475-6483,1991. 

HUANG, E. X., HUANG, Q. L WILDUNG, M. R CROTEAU, R SCOTT, A. I. Overproduction, in Escherichia coli, of soluble taxadiene synthase, a key enzyme in the taxol biosynthetic pathway, Protein Expression Purification, 1998,13,90-%. 

Excessive production of liver 5-aminolevulinate synthase causes two forms of congenital porphyria. These diseases are characterized by overproduction of porphyrins and excretion of large amounts of 5-aminolevulinate and porphobilinogen. Some ethnic groups have a high incidence of this disease, and in these people, acute attacks are brought on by barbiturates and other compounds that induce synthesis of the enzyme. 

Mutants constitutive for IP synthase activity were identified on the basis of a phenotype associated with overproduction of mositol (Opi- phenotype) and the subsequent excretion of inositol which can be detected in a bioassay (Greenberg et al., 1982b). Mutants at the OPI1 locus were shown to overexpress IP synthase activity and cross-reacting material, regardless of the presence of exogenous... 

Meier JL, Mercer AC, Rivera H, Burkart MD. Synthesis and 36. evaluation of bioorthogonal pantetheine analogues for in vivo protein modification. J. Am. Chem. Soc. 2006 128 12174-12184. Lambalot RH, Walsh CT. Cloning, overproduction, and characterization of the Escherichia-coli Holo-Acyl carrier protein synthase. 37. 

Activation of glutamate receptors of each sub-type leads to increase in intracellular ROS level [12,25,26] — mainly, SAR and hydroxyl radical, as well as Ca-dependent stimulation of NO-synthase, which results in appearance of NO-radical [27]. When arginine is in deficit, NO-synthase may generate SAR [28], Under conditions of overproduction of... 

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