Cells overproduction

Correct answer = A. Methotrexate interferes with folate metabolism by acting as a competitive inhibitor of the enzyme dihydrofolate reductase. This starves cells for tetrahydrofolate, and makes them unable to synthesize purines and dTMP This is especially toxic to rapidly-growing cancer cells. Overproduction of dihydrofolate reductase, usually caused by amplification of its gene, can overcome the inhibition of the enzyme at the methotrexate concentrations used for chemotherapy, and can result in resistance of the tumor to treatment by this drug. 

Mutations or chromosomal translocations that permit RTKs for growth factors to dimerize in the absence of their normal ligands lead to constitutive receptor activity (see Figures 23-14 and 23-15). Such activation ultimately induces changes in gene expression that can transform cells. Overproduction of growth factor receptors can have the same effect and lead to abnormal cell proliferation. 

Other biochemical changes include depressed serum concentrations of calcium and inorganic phosphate, largely because of insufficient intestinal absorption directly relating to too Httle of these ions in the usual diet. Serum alkaline phosphatase, especially bone-specific alkaline phosphatase, is elevated because of osteoblastic cell overproduction when these cells attempt to form new bone tissue. 

Many kinds of amino acids (eg, L-lysine, L-omithine, t-phenylalanine, L-threonine, L-tyrosine, L-valine) are accumulated by auxotrophic mutant strains (which are altered to require some growth factors such as vitamins and amino acids) (Table 6, Primary mutation) (22). In these mutants, the formation of regulatory effector(s) on the amino acid biosynthesis is genetically blocked and the concentration of the effector(s) is kept low enough to release the regulation and iaduce the overproduction of the corresponding amino acid and its accumulation outside the cells (22). 

Situated as it is between glycolysis and the electron transport chain, the TCA cycle must be carefully controlled by the ceil. If the cycle were permitted to run unchecked, large amounts of metabolic energy could be wasted in overproduction of reduced coenzymes and ATP conversely, if it ran too slowly, ATP would not be produced rapidly enough to satisfy the needs of the cell. Also, as just seen, the TCA cycle is an important source of precursors for biosynthetic processes and must be able to provide them as needed. 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

Elroy-Stein, D., Bernstein, Y. and Groner, Y. (1986). Overproduction of human Cu/Zn-superoxide dismutase in transfected cells extenuation of paraquat-mediated cytotoxicity and enhancement of lipid peroxidation. EMBO J. 5, 615-622. 

A. Chatterjee, Y. Cui, Y. Liu, C. K. Dumenyo, A. K. Chatterjee, Inactivation of rsmA leads to overproduction of extracellular pectinases, cellula.ses, and proteases in Erwinia carotovora subsp. carotovora in the absence of the starvation/cell densitysensing signal, N-(3-oxohexanoyl)-L-homoserine lactone. AppL Environ. Microbiol. 6/ 1959 (1995). 

F9. Fujii, H., Miwa, S., Tani, K., Fujinami, N., and Asano, H., Overproduction of structurally normal enzyme in man Hereditary hemolytic anemia with increased red cell adenosine deaminase activity. Br. J. Haematol. 51,427-430 (1982). 

M22. Miwa, S., Fujii, H Matsumoto, N Nakatsuji, T., Oda, S., Asano, H Asano, S., and Miura, Y A case of red-cell adenosine deaminase overproduction associated with hereditary hemolytic anemia found in Japan. Am. J. Hematol. 5, 107-115 (1978). 

Virus infection obviously upsets the regulatory mechanisms of the host, since there is a marked overproduction of nucleic acid and protein in the infected cell. In some cases, virus infection causes a complete shutdown of host macromolecular synthesis while in other cases host synthesis proceeds concurrently with virus synthesis. In either case, the regulation of virus synthesis is under the control of the virus rather than the host. There are several elements of this control which are similar to the host regulatory mechanisms, but there are also some uniquely viral regulatory mechanisms. We discuss various regulatory mechanisms when we consider the individual viruses later in this chapter. 

Yukimune, Y., Tabata, H., Higashi, Y. and Hara, Y. (1996) Methyl jasmonate-induced overproduction of paclitaxel and baccatin III in Taxus cell suspension cultures. Nature Biotechnology, 14, 1129-1132. 

Poly(3HB) is usually produced in a batch or fed-batch regime. These types of process control are derived from the general observation that overproduction of poly(3HB) occurs when cell multiplication is limited by an essential nutrient and the carbon substrate is available in excess. Batchwise production has an advantage in that a high poly(3HB) content can be reached. One disadvantage is the quality of the product, which can vary from one batch to the next. This can be overcome by a continuous process. Continuous production is basically possible if ... 

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 ROS can be harmful. Thus, cells have developed a complex antioxidant defense system to counteract the biological potential of ROS formation [213],... 

Gardner et al. [165] have shown that the redox-cycling agent phenazine methosulfate (PMS), mitochondrial ubiquinol-cytochrome c oxidoreductase, or hypoxia inactivated aco-nitase in mammalian cells. It has been proposed that the inactivation of aconitase is mediated by superoxide produced by prooxidants because the overproduction of mitochondrial MnSOD protected aconitase from inactivation by the prooxidants mentioned above except hyperoxia. Later on, the reaction of superoxide with aconitases began to be considered as one of the most important ways to NTBI generation in vivo. 

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