Elucidate metabolic pathways

No studies were located regarding methods for reducing body burden or methods for interfering with the mechanism of action for toxic effects. Also, no definitive studies were located regarding the metabolic fate of white phosphorus after absorption. Therefore, studies elucidating metabolic pathways would be helpful as baseline data for developing methods for reducing body burden. 

MetaCyc SRI International Database of nonredundant, experimentally elucidated metabolic pathways—1,790 pathways from more than 2,216 different organisms (http //metacyc.org/)... 

MetaCyc (5) is a multiorganism encyclopedia of metabolic pathways and enzymes. Like EcoCyc, it contains literature-derived information on experimentally elucidated metabolic pathways and enzymes. MetaCyc version 10.5 (October 2006) contains all... 

Isotopic tracers have been extremely useful in elucidating metabolic pathways. Precursor-product relationships (i.e., the sequence of reactions) can be established by introducing a very smalt amount of highly labeled suspected precursor into the system and then following the appearance of label in the other intermediates an l the final product. The mass in the labeled precursor should be very smalfso that the steady-state pool sizes of the various intermediates do not change. For example, consider the sequence shown below w here we suspect that C is an intermediate in the pathway from A to D. 

The details of the methods used in elucidating metabolic pathways inevitably depend on the particular organisms studied, but the most common approach involves administration of isotopically labelled compounds and detection of the label in metabolic intermediates. Work on whole animals and plants is subject to certain obvious limitations. For example ... 

Having many active synergistic constituents (a multicomponent character) interacting with multiple receptors in the human body is seen as a major advantage of TCMs and pivotal for the overall therapeutic effect [2]. However, the multicomponent character is also a major obstacle for the quantitation of components, identification of structures, explanation of the mode of action, and elucidating metabolic pathways. To date, himdreds of papers report on the simultaneous determination of multiple components in crude materia medica or finished TCMs [10,12—20]. 

Radioactive isotopes are widely used as tracers or labels for substances separated by TLC for following the causes of chemical and biochemical reactions, determining the distribution of substances in a reaction mixture, elucidating metabolic pathways of drugs, pesticides, pollutants, and natural substances in human, animal and plant tissues, and assessing the purity of isotopes. The most widely used labelled substances in TLRC contain (tritium) and... 

All overview of the glycolytic pathway is presented in Figure 19.1. Most of the details of this pathway (the first metabolic pathway to be elucidated) were worked out in the first half of the 20th century by the German biochemists Otto Warburg, G. Embden, and O. Meyerhof. In fact, the sequence of reactions in Figure 19.1 is often referred to as the Embden-Meyerhof pathway. 

Cyclic nitrosamines are among the most potent and environmentally significant nitrosamine carcinogens. Like the acyclic nitrosamines, metabolism is necessary for their carcinogenicity. Elucidation of the specific metabolic pathways of cyclic nitrosamine activation and detoxification is a challenging problem, and considerable progress has been achieved in recent years. In this chapter, we will review metabolic studies on N-nitrosopyrrolidine (NPYR), N -nitrosonornicotine (NNN), N-nitrosopiperidine (NPIP), N-nitrosohexamethyleneimine (NHEX), N-nitrosomorpholine (NMOR),... 

Elucidation of more complex metabolic pathways includes the following ... 

Elucidation of the Unexpected Complexity of an Apparently Straightforward Metabolic Pathway... 

Oldfield C, O Pogrebinsky, J Simmonds, ES Olson, CE Kulpa (1997) Elucidation of the metabolic pathway for dibenzothiophene desulphurization by Rhodococcus sp. strain IGTS8 (ATCC 53968). Microbiology (UK) 143 2961-2973. 

Certainly, the identification of the degradation products responsible for the cytotoxic effects and their metabolic pathways require a thorough elucidation, and a cultured RPE offers a good model for these investigations. 

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