Mammals metabolic pathways

A substantial fraction of the named enzymes are oxido-reductases, responsible for shuttling electrons along metabolic pathways that reduce carbon dioxide to sugar (in the case of plants), or reduce oxygen to water (in the case of mammals). The oxido-reductases that drive these processes involve a small set of redox active cofactors , that is, small chemical groups that gain or lose electrons. These cofactors include iron porjDhyrins, iron-sulfur clusters and copper complexes as well as organic species that are ET active. 

Ishii and coworkers examined microbial transformations of lysergic acid and related compunds in order to clarify the metabolic pathway of LSD in mammals (162-164). Steptomyces lavendulae (IFM 1031) accomplished selective N-de-methylation at position N6 of lysergic acid diethylamide (LSD) (37) to afford nor-LSD (38) (162). On the other hand, S. roseochromogenes (IFM 1081) ac-... 

Recent work in our laboratories has confirmed the existence of a similar pathway in the oxidation of vindoline in mammals (777). The availability of compounds such as 59 as analytical standards, along with published mass spectral and NMR spectral properties of this compound, served to facilitate identification of metabolites formed in mammalian liver microsome incubations. Two compounds are produced during incubations with mouse liver microsome preparations 17-deacetylvindoline, and the dihydrovindoline ether dimer 59. Both compounds were isolated and completely characterized by spectral comparison to authentic standards. This work emphasizes the prospective value of microbial and enzymatic transformation studies in predicting pathways of metabolism in mammalian systems. This work would also suggest the involvement of cytochrome P-450 enzyme system(s) in the oxidation process. Whether the first steps involve direct introduction of molecular oxygen at position 3 of vindoline or an initial abstraction of electrons, as in Scheme 15, remains unknown. The establishment of a metabolic pathway in mammals, identical to those found in Strep-tomycetes, with copper oxidases and peroxidases again confirms the prospective value of the microbial models of mammalian metabolism concept. 

Such observations as these should inject caution into those who speak glibly about what metabolism is like in the mammalian organism. Furthermore, if differences such as these exist among different species of higher mammals, it lends credence to the idea that, within the human species, quantitative differences of a similar nature may exist. Because of differences in enzyme systems and the extent to which different metabolic pathways are utilized in different individuals, it is not at all unreasonable to conclude that different individuals probably have fundamental needs for quite different levels of the thyroid hormone. 

Figure 6. Simplified scheme of metabolic pathways of cis-chlordane in fish (Route A), desaturation and epoxidation and (Route B), hydroxylations. Both routes are operative in cichlids (as in mammals). Goldfish and bluegills seem to...

It is apparent that the aquatic echinoderm and terrestrial mammal deal with a chemical probe by very different metabolic pathways. The exclusive formation of oxidized ((T-demethylated) product in the mouse may partly reflect the animal s highly oxidizing environment, while the relatively anoxic marine environment is represented in the observed reduced metabolites of the sea urchin. 

Fig. 9.15. Metabolism of acephate (9.82) in mammals [156]. Pathway a leads to toxification by producing methamidophos. Pathways b-d are reactions of detoxification that lead to an O-demethyl, a demethylthio, and a deacetylamino metabolite, respectively.

Dihydropyrimidine dehydrogenase is the first and the rate-limiting enzyme in the three-step metabolic pathway involved in the degradation of the pyrimidine bases uracil and thymine. In addition, this catabolic pathway is the only route for the synthesis of p-alanine in mammals. 

The results of a comparative metabolism study of an aryl-sulfenyl derivative of carbofuran [2,2-dimethy1-2,3-dihydro-benzofuranyl-7 -methyl-N-(2-toluenesulfenyl)carbamate] in the house fly and white mouse Indicated the selective action of this compound to be a consequence of different metabolic pathways in insects and mammals (12). The arylsulfenyl group on the carbamate moiety allows the mammal to carry out metabolic reactions leading to less toxic products which are rapidly conjugated, while the toxic parent methylcarbamate is formed in the insect. 

Another study (202) of sulfadiazine pharmacokinetics in carp treated by the intraperitoneal route showed an elimination half-life of 17.5 h at 20 C. Both acetylation and hydroxylation metabolic pathways appeared to occur, but they only represented 2% and 0.41 % of the dose, respectively. This is in strong contrast to the metabolism profile of sulfadiazine in mammals, where hydroxylation is much more important. 

Figure 1. Metabolic pathways of butadiene, as deduced from findings in mammals in vitro and in vivo... 

Chapters 20 through 22 describe the major anabolic pathways by which cells use the energy in ATP to produce carbohydrates, lipids, amino acids, and nucleotides from simpler precursors. In Chapter 23 we step back from our detailed look at the metabolic pathways—as they occur in all organisms, from Escherichia coli to humans—and consider how they are regulated and integrated in mammals by hormonal mechanisms. 

To figure out the biological meaning of the crossover (Figure 2.9 (C-E)), we need to know why this occurs. In mammals the answer seems to be a simple conseqence of power obtainable from different metabolic pathways maximum ATP turnover rates supported by fat oxidation in mammals are only about two-thirds the maximum ATP turnover rates supportable by glycogen oxidation (figure 2.10). The reasons for... 

All of the above discussion on the functional properties of metabolic pathways has focused on short-term responses. The question arises of the effects of adjustments over acclimation or intermediate time courses because studies with humans and mammals dominate this field, we will refer to these as training effects rather than acclimations (the term that is used elsewhere throughout this book). 

In mammals, 25% of the protein in the body is collagen it provides the scaffold that holds the entire body together. Movement is provided almost entirely by interactions of actin with myosin (making muscle) or of kinesin/dynein with microtubules (see also Chapter 21). Few animal materials have the chemical stability of cellulose probably only chitin (primarily in arthropods and fungi, but also part of the metabolic pathway of other animals including man) and elastin. 

Figure 8.24 Metabolic pathways of carbaryl in mammals and insects. (From Menzie, C.M., U.S. Department of the Interior Fish and Wildlife Service, Special Scientific Report—Wildlife No. 212. Washington, D.C., 1978.)...

Figure 8.26 Metabolic pathways of diazinon in mammals and insects. (Redrawn from Aizawa, H., Metabolic Maps of Pesticides, Academic Press, New York, 1982.)...

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