Proteins metabolic enzymes

Proteins other than histones can also be modified by Lys acetylation. Many transcription factors, cytoskeleton proteins, metabolic enzymes, and signaling proteins are acetylated (55). 

Group II assays consist of those monitoring cellular second messengers. Thus, activation of receptors to cause Gs-protein activation of adenylate cyclase will lead to elevation of cytosolic or extracellularly secreted cyclic AMP. This second messenger phosphorylates numerous cyclic AMP-dependent protein kinases, which go on to phosphorylate metabolic enzymes and transport and regulatory proteins (see Chapter 2). Cyclic AMP can be detected either radiometrically or with fluorescent probe technology. 

Plants are constantly subject to adverse environmental conditions such as drought, flooding, extreme temperatures, excessive salts, heavy metals, high-intensity irradiation and infection by pathogenic agents. Because of their immobility, plants have to make necessary metabolic and structural adjustments to cope with the stress conditions. To this end, the expression of the genetic programme in plants is altered by the stress stimuli to induce and/or suppress the production of specific proteins which are either structural proteins or enzymes for specific metabolic pathways. 

The first is cell injury (cytotoxicity), which can be severe enough to result in cell death. There are many mechanisms by which xenobiotics injure cells. The one considered here is covalent binding to cell macromol-ecules of reactive species of xenobiotics produced by metabolism. These macromolecular targets include DNA, RNA, and protein. If the macromolecule to which the reactive xenobiotic binds is essential for short-term cell survival, eg, a protein or enzyme involved in some critical cellular function such as oxidative phosphorylation or regulation of the permeability of the plasma membrane, then severe effects on cellular function could become evident quite rapidly. 

Hansch and Leo [13] described the impact of Hpophihdty on pharmacodynamic events in detailed chapters on QSAR studies of proteins and enzymes, of antitumor drugs, of central nervous system agents as well as microbial and pesticide QSAR studies. Furthermore, many reviews document the prime importance of log P as descriptors of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties [5-18]. Increased lipophilicity was shown to correlate with poorer aqueous solubility, increased plasma protein binding, increased storage in tissues, and more rapid metabolism and elimination. Lipophilicity is also a highly important descriptor of blood-brain barrier (BBB) permeability [19, 20]. Last, but not least, lipophilicity plays a dominant role in toxicity prediction [21]. 

The major determinant of myocardial redox status is the glutathione content of the heart (Griffith and Meister, 1979). Therefore, fluctuations in myocardial glutathione status may exert a regulatory role in cellular metabolism in a comparable manner to the phosphorylation and dephosphorylation of proteins and enzymes. 

Tirmenstein, M.A. and Nelson, S.D. (1990). Acetaminophen-induced oxidation of protein thiols contribution of impaired thiol metabolizing enzymes and the breakdown of adenine nucleotides. J. Biol. Chem. 2265, 3059-3065. 

Hepatocytes, whether freshly cultured or cryo-preserved, can provide an assessment of not only CYP metabolism but also clearance by other metabolizing enzymes and potentially the role of transporters [51]. The accuracy of the data is of course dependent on how well the proteins in the hepatocytes function after culturing or freezing. 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Organic contaminants such as petroleum hydrocarbons or chlorinated solvents can be directly metabolized by proteins and enzymes, leading to the degradation, metabolism, or mineralization of the contaminants. Furthermore, many of these contaminants can be broken down into harmless products or converted into a source of food and energy for the plants or soil organisms.50... 

From the above, it is clear that the gut wall represents more than just a physical barrier to oral drug absorption. In addition to the requirement to permeate the membrane of the enterocyte, the drug must avoid metabolism by the enzymes present in the gut wall cell as well as counter-absorptive efflux by transport proteins in the gut wall cell membrane. Metabolic enzymes expressed by the enterocyte include the cytochrome P450, glucuronyltransferases, sulfotransferases and esterases. The levels of expression of these enzymes in the small intestine can approach that of the liver. The most well-studied efflux transporter expressed by the enterocyte is P-gp. 

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