Genetic control levels

Mefabo//sm - The half-life of INH is widely variable and dependent on acetylator status. Isoniazid is primarily acetylated by the liver this process is genetically controlled. Fast acetylators metabolize the drug about 5 to 6 times faster than slow acetylators. Several minor metabolites have been identified, one or more of which may be reactive (monoacetylhydrazine is suspected), and responsible for liver damage. The rate of acetylation does not significantly alter the effectiveness of INH. However, slow acetylation may lead to higher blood levels of the drug, and thus to an increase in toxic reactions. 

But many metabolic processes are likely to influence amino acid blood levels and urinary excretion both ways, some of which may be genetically controlled specifically or else may be influenced by a variety of body functions. Endocrine factors have for instance been taken into consideration in the case of histidinuria (S22). It seems, however, that in our present state of knowledge we are still altogether insufficiently informed about amino acid blood levels and on their possible fluctuations. As long as the data published in the literature on amino acidemia remain as scarce as they are at the present time, we feel that our knowledge of the... 

Yesell ES, Page JG. Genetic control of dicumerol levels in man. J Clin Invest 1968 47 2657-2663. 

The enzyme concentration in cells is regulated at the synthetic level by genetic control (Gottesman, 1984), which may occur positively or negatively. 

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. 

Data with a polymodal distribution If we give a series of patients a standard oral dose of the anti-tuberculosis drug isoniazid, obtain a blood sample from each individual 6 h later and determine the isoniazid concentrations of those samples, the results will probably look like Figure 3.1. The data are bimodal, because the metabolism of isoniazid is genetically controlled and we all fall into one of two groups - fast or slow metabolizers. The fast metabolizers form the cluster at the low end of the concentration scale and the slow metabolizers form a distinct group with higher levels. 

Because of the ease of qualitative analysis, first through distillation to isolate major components and, subsequently, through GLC, volatile oils have consistently attracted the attention of chemotaxonomists. These oils are almost invariably complex mixtures in which monoterpenes and/or sesquiterpenes usually predominate, although the bios)mthetically unrelated phenylpropanes can also be important. Some of the earliest studies on the genetic control of SM involved the oils of mints, Mentha (Murray, 1960). Volatile oils yielded the first properly documented examples of chemical races (Penfold and Morrison, 1927 Sutherland and Park, 1967), while Zavarin and co-workers (1971) provided clear evidence for the impact of environmental factors on the composition of volatile oil. Because of the comparative nature of GLG analysis, volatile oils were among the first compounds to be extensively studied at the population level and to be subjected to numerical analysis. The work of Adams on Juniperus in south-eastern USA... 

Vesell, E.S. Page, J.G. Genetic control of drug levels in man antipyrine. Science 1968,161, 72-73. 

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