Metabolic rate factors affecting

The engineered bioremediation system (EBS) is a proprietary process for the ex situ bioremediation of organic contaminated soils. The system is designed to enhance the natural bioremediation rate of organic constituents by controlling factors affecting microbial growth and metabolism. 

Apart from the site and route of administration, formulation, dosage, and duration of treatment, biotransformation is often also affected by several other factors including age, species differences, sex differences, diet, diseases, hormones, and environment. The activity of the liver microsomal enzymes is low in newborns and aging animals resulting in a slower rate of biotransformation. Species differences in dosage and response are often due to biotransformation differences. Inadequate protein intake approaching starvation may also decrease the rate of biotransformation (12). Diseases of the liver sometimes also interfere with the normal biotransformation capacity. In addition, increase in biotransformation may occur at high body temperatures because of an increase in the metabolic rate. 

A number of factors can influence the balance between the rate of formation of reactive metabolites and the rate of removal, thereby affecting toxicity. The major factors discussed in this chapter are summarized in the following subsections. A more in-depth discussion of other factors affecting metabolism and toxicity are presented in Chapter 9. 

Factors affecting the rate of synthesis include the level of induction or repression of the gene encoding the enzyme (see Topics G3 and G4 and also the rate of degradation of the mRNA produced from that gene. Many key enzymes at control points in metabolic pathways have particularly short-lived mRNAs and the rate of enzyme synthesis is thus readily controlled by factors that affect the rate of gene transcription. 

One example is the known interference by reducing compounds that affect the chemical conversion of substrate to a colored indicator. This is especially true for the tetrazolium assays (Ulukaya, Colakogullari, and Wood 2004 Chakrabarti et al. 2000 Pagliacci et al. 1993 Collier and Pritsos 2003). The growing list of interfering compounds includes ascorbic acid and sulfhydryl reagents such as glutathione, coenzyme A, dithiothreitol, etc. Similar interferences by compounds that affect the oxidation and reduction chemistry of cells are likely to cause artifacts with the resazurin reduction assay. Assays that measure markers of metabolism also can be influenced by the pH of the culture medium and other factors that may stimulate or stress the metabolic rates of cells. 

The Navy should be aware that the altered atmospheric conditions on a disabled submarine would affect the toxicity of the gases. For example, cold temperatures will cause crew members to shiver this will increase the rate of respiration because of an increase in metabolic rate. Lower air temperature might also result in the crew s breathing unconditioned air, which is a risk factor for lowerairway disease and airway hyperactivity. However, data are lacking on the precise magnitude of effects therefore, the Navy should conduct research to determine the nature and magnitude of the effects from altered submarine atmospheric conditions. 

The intensity of illumination is known to affect the activity of many insects, and therefore may affect insecticide tolerance through the metabolic rate or through uptake rate in the case of residual treatment in a confined environment. Although both factors operate in the same way, it is not surprising that houseflies are more sensitive to DDT residues in light than in darkness. 

Furthermore, pharmacokinetic administration, distribution, metabolism and excretion (ADME) factors affect drug bioavailability, efficacy and safety, and, thus, are a vital consideration in the selection process of oral drug candidates in development pipelines. Since solubility, permeability, and the fraction of dose absorbed are fundamental BCS parameters that affect ADME, these BCS parameters should prove useful in drug discovery and development. In particular, the classification can used to make the development process more efficient.For example, in the case of a drug placed in BCS Class II where dissolution is the rate-limiting step to absorption, formulation principles such as polymorph selection, salt selection, complex formation, and particle size reduction (i.e., nanoparticles) could be applied earlier in development to improve bioavailability. 

The alteration of fermentation conditions, such as pH, drastically affects product concentrations. Research with C. ljungdahlii has shown that at high pH values (5.5-6), acetate was the dominant product, while at a lower pH (4-4.5), there was a drastic shift towards the production of ethanol. " Inhibition by end products or intermediates is the principal factor that limits metabolic rates and final product concentrations in many fermentation processes. Product inhibition can greatly affect the economics of commercialization. With regards to ethanol inhibition, growth of B. methylotrophicum was inhibited at alcohol concentrations of 5g/L. " However, a recently isolated clostridial strain was shown to tolerate ethanol concentrations up to 78g/L. Efforts have been made to eliminate the drawbacks of inhibition by improvement of bacterial strains to tolerate higher product concentrations and/or by use of novel separation coupled fermentation processes such as pervaporation, extraction, and membrane separation. 

Thus, the distribution of the parent compound or metabolite(s) into the target tissue(s), metabolism and excretion in such tissues and the interaction with receptors or other critical cellular macromolecules are all dynamic processes occurring at particular rates. Factors which affect these processes therefore will influence toxicity and the particular target organ, and may even change the target organ. 

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