Biological consequences

As previously recalled, enzymatic CTI in eukaryotic cells is unknown and the presence of trans fatty acid isomers in humans has been generally attributed to exogenous sources. After a series of studies in several countries it was found that trans fatty acid isomers can give harmful effects on health, involving risk factors of heart attack and coronary artery disease, impairment of fetal and infant growth 

Whether an endogenous path by free radical transformation could account for trans isomer formation had still not been demonstrated, until recently. The working hypothesis started from the fact that several radical-based processes occur during normal cell metabolism [44], and a certain number of thiyl radicals could be derived from the intracellular sulfur-containing compounds. From the biomimetic models described in the previous section, it was clear that an isomerization process, not to be confused with a dietary contribution, could be evaluated by the detection of mono-trans isomers of arachidonate in membrane phospholipids. 

The isomer trends of the models were very useful for helping the identification of isomers. Cell cultures of human leukemia cell lines (THP-1) were incubated in the absence and presence of thiol compounds, ensuring that no trans compounds could come from the medium [45]. In parallel experiments, some millimolar levels of thiol compounds were added to the cell cultures during incubation, and the comparison of isomeric trends was carried out. A basic content of trans lipids in THP-1 cell membranes could be found during their growth without thiol, and after the addition of the amphiphilic 2-mercaptoethanol, it increased to 5.6% of the main fatty acid residues. Moreover, when a radical stress by y-irradiation is artificially produced in the cell cultures added with thiol, a larger isomerization effect could be seen, with trans lipid formation up to 15.5% in membrane phospholipids. The fatty acid residues most involved in this transformation were arachidonate moieties, as expected. 

This result can be considered as the first evidence for a geometrical change induced in the biological environment under radical stress, and it opens new perspectives for the role of trans lipids in the lipidome of eukaryotic cells. 

We have previously mentioned that lipids make part of the membrane architecture, which has the typical bilayer arrangement due to the phospholipid supramo-lecular organization. This leads to biological consequences - the composition of fatty acid residues with saturated and unsaturated hydrocarbon chains is crucial to regulate membrane properties, maintaining the best balance for cellular functioning and also survival. Vesicle models made of phosphatidylcholines with saturated and unsaturated fatty acid residues are useful for studies of permeability and fluidity. Several studies have compared the effects of saturated, cis and trans unsaturated residues. An example is given in Fig. 6.4 for vesicles made up of different phospholipid compositions. 

It was said that reduction as well as oxidation of proteins lead to polypeptidic backbone modifications, fragmentation, dimerization or polymerization. Three 

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From a bioavailabihty standpoint, the fact that a significant amount of nicotinic acid is in a bound form has important biological consequences. Poor bioavailabihty stems from the fact that the ester linkage is resistance to digestive enzymes. In the case of com, this condition can be alleviated if com is pretreated with alkah. This food preparation method is frequently practiced in Mexico for the preparation of tortillas. 

Kinase Inhibitors Mechanism of Action Biological Consequences... 

Grue, C.E., Hart, A.D.M., andMineau, P. (1991). Biological consequences of depressed brain cholinesterase activity in wildlife. In Mineau, P. (Ed.) Cholinesterase Inhibiting Insecticides— Their Impact on Wildlife and the Environment, 151-210. Amsterdam Elsevier. 

The complex series of events in collagen maturation provide a model that illustrates the biologic consequences of incomplete polypeptide maturation. The best-known defect in collagen biosynthesis is scurvy, a result of a dietary deficiency of vitamin C required by... 

Chemokine Protease Product Biological consequences References... 

Lands, W.E.M. (1984). Biological consequences of fatty acid oxygenase reaction mechanisms. Prost. Leuko. Med. 13, 35-46. 

Second is the application of a wide range of experimental designs and techniques. DNA CT is observed in a diverse array of systems over different distance and time regimes. Consequently, a versatile approach which draws upon complementary methods is required to explore different facets of this chemistry and develop a complete picture. We interrogate a variety of nucleic acid assemblies using spectroscopic, biochemical and electrochemical tools to define mechanistic features, exploit biological applications, and explore biological consequences of DNA CT. 

Applications and Biological Consequences of DNA-Mediated Charge Transport... 

While CT mediated by the DNA base stack may not be completely characterized mechanistically, that it does occur is undeniable. This remarkable chemistry, inherent to DNA, has opened the door to a myriad of possible applications, and provoked intriguing questions regarding biological consequences. 

Mark, J., Bailey, M.J., Ronald, G. and Dickinson, R.G. (2003) Acyl glucuronide reactivity in perspective biological consequences. Chemico-Biological Interactions, 145, 117-137. 

Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 2000 61 154-166. 

The interstrand cross-link also induces DNA bending.72 X-ray and NMR studies on this adduct show that platinum is located in the minor groove and the cytosines of the d(GC) base pair involved in interstrand cross-link formation are flipped out of the helix stack and a localized Z-form DNA is observed.83-85 This is a highly unusual structure and very distorting—implications for differential repair of the two adducts have been addressed. Alternatively, the interstrand cross-link of the antitumor inactive trans-DDP is formed between a guanine (G) and its complementary cytosine (C) on the same base p a i r.86,87/ nms- D D P is sterically incapable of producing 1,2-intrastrand adducts and this feature has been cited as a dominant structural reason for its lack of antitumor efficacy. It is clear that the structural distortions induced on the DNA are very different and likely to induce distinctly different biological consequences. 

Due to the numerous possible reactions and related biological consequences, inappropriate overproduction of NO can cause a series of disease states such as a variety of neurodegeneration diseases including inflammation, rheumatic disease, septic shock, diabetes melhtus, and cerebral ischemia. Therefore development of isoform-specific NOS inhibitors to regulate NO synthesis has been an active research area. 

Biochemical and Biological Consequences of Changing the Specificity of p21(Ras) from Guanosine to Xantho-sine Nucleotides, G. Schmidt, C. Lenzen, I. Simon, R. Deuter, R. H. Cool, R. S. Goody, A. Wittinghofer, Oncogene 1996,12, 87-96. 

Alvarez MG, Prucca C, Milanesio ME, Durantini EN, Rivarola V (2006) Photodynamic activity of a new sensitizer derived from porphyrin-C60 dyad and its biological consequences in a human carcinoma cell line. Int J Biochem Cell Biol 38 2092-2101. 

Idee JM, Port M, Raynal I, Schaefer M, Le Greneur S, Corot C (2006) Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging a review. Fundam. Clin. Pharmacol. 20 563-576. 

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