Enzyme amount physiological mechanisms

Adrenaline and noradrenaline are unstable in aqueous solution where they are subjected to spontaneous oxidation. In vivo this mechanism is only relevant under pathophysiological conditions of an catecholamine excess, since two enzymes, the catechol-O-methyltransferase (COMT) and the monoamineoxidase (MAO), inactivate physiological amounts of the transmitters. There are at least two subtypes of the enzyme MAO, A and B, which can be inhibited selectively for therapeutic purposes, for example by moclobemide and selegiline. 

As noted earlier, the velocity of any enzyme-catalyzed reaction is dependent upon the amount of effective enzyme present. Enzyme biosynthesis, like that of all proteins, is under genetic control, a long-term process. Biosynthesis of enzymes may be increased or decreased at the genome level. Various hormones can activate or repress the mechanisms controlling gene expression. Enzyme levels are the result of the balance between synthesis and degradation. This enzyme turnover may be altered by diverse physiological conditions, by hormone effects, and by the level of metabolites. 

To be used effectively, the mechanisms through which inhibitors exert their effects need to be understood. For example, competitive inhibitors compete with physiological substrates for binding sites. Their effect depends on the relative concentrations of substrates and the inhibitor and the degree of inhibition depends on the number of active sites occupied by the inhibitor versus the metabolic substrate. In contrast, noncompetitive inhibitors bind to parts of the enzyme other than the substrate binding site, so the degree of inhibition depends only on the inhibitor and not the substrate concentration. This type of inhibition is typically irreversible and reduces the amount of total enzyme available to catalyze a particular reaction. Uncompetitive inhibition occurs when the inhibitor binds to the enzyme-substrate complex and prevents the reaction from being catalyzed. 

Just as physiological patterns of control over metabolite flow can be recognized, so can physiological patterns of control over the amount of enzyme. Table III lists a convenient classification. Clearly, the amount of enzyme at any time is a summation of the amount formed and the amount destroyed. Two specific patterns controlling formation might be recognized repression by endproducts and induction by substrate or a precursor. It should be stressed that the terms "repression" and "induction" are operational and should carry no connotations regarding the mechanisms. 

The body has a wide array of very effective defense mechanisms which protect it from toxins. This initial response of the body is a process of physiological adaptation. This includes such phenomena as enzyme induction, hormonal changes, alterations in blood flow, blood cell distribution, energy utilization, immunologic responses, as well as the rate of cell division and cell destruction. This process of adaptation is not considered to be evidence of toxicity it s the body s normal response to an insult. When the amount of insult exceeds the body s ability to maintain itself, toxicity exists. The transition from physiological adaptation to a toxic response can be considered a threshold. 

---