Types of Metabolic Change

Oxidation Sulfation Further metabolism of glutathione conjugates 

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Irreversible inhibition, which is much more important toxicologically, can arise from various causes. In most cases the formation of covalent or other stable bonds or the disruption of the enzyme structure is involved. In these cases the effect cannot be readily reversed in vitro by either dialysis or dilution. The formation of stable inhibitory complexes may involve the prior formation of a reactive intermediate that then interacts with the enzyme. An excellent example of this type of inhibition is the effect of the insecticide synergist piperonyl butoxide (Figure 9.6) on hepatic microsomal monooxygenase activity. This methylenedioxyphenyl compound can form a stable inhibitory complex that blocks CO binding to P450 and also prevents substrate oxidation. This complex results from the formation of a reactive intermediate, which is shown by the fact that the type of inhibition changes from competitive to irreversible as metabolism, in the... 

Six common metabolic reactions (enzyme, type of structural change, and relative rates). 

Insulin and the counterregulatory hormones exert two types of metabolic regulation (see Chapter 26). The first type of control occurs within minutes to hours of the hormone-receptor interaction and usually results from changes in the catalytic activity or kinetics of key preexisting enzymes, caused by phosphorylation or dephosphorylation of these enzymes. The second type of control involves regulation of the synthesis of key enzymes by mechanisms that stimulate or inhibit transcription and translation of mRNA. These processes are slow and require hours to days. 

AG acts as a natural AA precursor whose metabolism by COX and generation of PGEj (an emetic agent) participates in positive modulation of inflammatory mediators such as NO production and COX-2 induction, which may induce certain types of vomiting (Chang et al., 2001 Jeon et al., 1996). 

Amino acid changes can be of a secondary nature and a clue to other types of metabolic disorders such as galactosemia, organic acidopathies and pyruvate metabolic disorders. 

Physiological effects of air pollution are deperrdent on dosage, the ability of the exposed organism to metabolize and excrete the pollution, and the type of pollutant. Many pollutants affect the futretiotring of the respiratory tract some change the structure and function of molecules others can enter the nucleus and turn getres otr or off atrd some cause chromosomal aberrations or mutations that result in cancer. 

FIGURE 5.3 Different types of functional readouts of agonism. Receptors need not mediate cellular response but may demonstrate behaviors such as internalization into the cytoplasm of the cell (mechanism 1). Receptors can also interact with membrane proteins such as G-proteins (mechanism 2) and produce cytosolic messenger molecules (mechanism 3), which can go on to mediate gene expression (mechanism 4). Receptors can also mediate changes in cellular metabolism (mechanism 5). 

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