Metabohc

Triazines pose rather more of a problem, probably because the carbons are in an effectively oxidized state so that no metaboHc energy is obtained by their metaboHsm. Very few pure cultures of microorganisms are able to degrade triazines such as Atrazine, although some Pseudomonads are able to use the compound as sole source of nitrogen in the presence of citrate or other simple carbon substrates. The initial reactions seem to be the removal of the ethyl or isopropyl substituents on the ring (41), followed by complete mineralization of the triazine ring. 

Cleavage of C-17 JilkylSubstituents. Resulting primarily in cholan-17-ones, this is a relatively minor metabohc pathway. Corticosterone is not known to... 

C-6 Hydroyylation. This biotransformation is more predominant in infants than in adults, and can prevent other metabohc transformations. 

Compounds having the 16,17 ketal, eg, budesonide, amcinonide, fluocinonide, halcinonide, triamcinolone acetonide, and flurandrenohde, also undergo metabohsm by routes that parahel that of cortisol metabohsm. Unsymmetrical acetals such as budesonide are also metabolized by routes not available to the more metabohcahy stable symmetrical 16a,17a-isopropyhdiene-dioxysubstituted compounds (desonide, flunisohde, and triamcinolone acetonide). Isozymes within the cytochrome P450 3A subfamily are thought to catalyze the metabohsm of budesonide, resulting in formation of 16a-hydroxyprednisolone and 6P-hydroxybudesonide (19,20) (Fig. 3) in addition to the more common metabohc steps (oxidation via reduction of A, etc). 

Prior to this work, dietary fiber, of which ceUulose is oae of the more important constituents, was considered important primarily as a means of preventing or overcoming constipation. Otherwise, dietary fiber was considered to be a metaboHcally iaert substance. A large variety of diseases such as appendicitis, hiatus hernia, gallstones, ischemic heart disease, diabetes, obesity, dental caries, and duodenal ulcers are now suspected to be associated with the consumption of a highly refined diet (42). 

Certain factors and product precursors are occasionally added to various fermentation media to iacrease product formation rates, the amount of product formed, or the type of product formed. Examples iaclude the addition of cobalt salts ia the vitamin fermentation, and phenylacetic acid and phenoxyacetic acid for the penicillin G (hen ylpenicillin) and penicillin V (phenoxymethylpenicillin) fermentations, respectively. Biotin is often added to the citric acid fermentation to enhance productivity and the addition of P-ionone vastly iacreases beta-carotene fermentation yields. Also, iaducers play an important role ia some enzyme production fermentations, and specific metaboHc inhibitors often block certain enzymatic steps that result in product accumulation. 

A critical review of the toxicity of the haloalkyl phosphates and the potential metaboHc products is available (141). The toxicity of flame retardants used in textiles has also been reviewed (142). 

Because of the corrosive effects and discomfort associated with inhalation of fluorine, chronic toxicity does not occur. Although the metaboHc fate of fluorine is not clear, it does not seem that much is converted to fluoride ion in the body (107). Therefore comparisons to effects of fluoride ion poisoning, known as fluorosis, are probably incorrect. 

Many plant substances possess antivitamin D activity but the mode of action and in most cases the identity remain unknown. Rachitogenic factors have been observed in yeast. Because of the metaboHc interrelationships that exist between vitamin D, Ca, and P, it is sometimes difficult to differentiate between chelators of mineral elements and tme antivitamins. One reported vitamin D antagonist in oats was later identified as phytic acid (72). 

At various times, antivitamin factors specific to vitamin folic acid, and choline have been reported. However, it is uncertain whether these are tme antimetaboHtes or if they may result from metaboHc interrelationships with other dietary constituents. 

Cell Activation. Several studies have shown that platelets and white cells undergo shape changes when adhering to filter media. The cells are activated by contact with the filter media and form pseudopods which attach to the filter media. The cells membranes may need a certain degree of viabihty to be able to actively attach to the filter media. When white cells are treated with metaboHc inhibitors, the capabiUty of leukocyte reduction by the filter is reduced. 

This change is influenced by metaboHc hormone action rarely do any of the hormones or other influencing factors act independent of each other to regulate nutrient partitioning. Complex interactions aHow for integration of influences to accommodate a coordinated chronic regulation of nutrient use for maintenance or growth so that an animal may adapt to its environment (see Feeds AND FEED ADDITIVES). 

Mechanism of Action. Eew data are available that describe the effects of anaboHc steroids on protein metaboHsm even fewer data exist for assessment of direct effects of anaboHc steroids on Hpid metaboHsm in growing mminants. The lack of any consistent change in somatotropin, prolactin, insulin, or other metaboHc hormones (qv) in a total of 15 studies has been noted (1,38). 

Mechanism of Action. The mechanisms by which antibiotic adrninistration at subtherapeutic levels enhance growth rate and efficiency of gain in growing animals have not been clarified. Possible modes of action include disease control, nutrient sparing, and metaboHc effects. There is extensive evidence that the principal benefit from subtherapeutic use of antibiotics results from the control of harmfiil microorganisms. 

Evidence for consistent, positive metaboHc effects of feeding antibiotics is fragmented and inconclusive. Direct measurement of increased uptake of nutrients, ie, in vivo amino acids, glucose, or volatile fatty acids in mminants, have not been reported. 

Biorational approaches have proven useful in the development of classes of herbicides which inhibit essential metaboHc pathways common to all plants and thus are specific to plants and have low toxicity to mammalian species. Biorational herbicide development remains a high risk endeavor since promising high activities observed in the laboratory may be nullified by factors such as limitations in plant uptake and translocation, and the instabiHty or inactivity of biochemical en2yme inhibitors under the harsher environmental conditions in the field. Despite these recogni2ed drawbacks, biorational design of herbicides has shown sufficient potential to make the study of herbicide modes of action an important and growing research area. 

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