Additional Metabolic Pathways

A diverse cross section of enzymes has been studied in Jerusalem artichoke (Table 10.8), some simply because the tuber provides a convenient source that can be easily stored. In other instances, especially where there are relatively unique properties involved, the focus has been on the role of the enzyme system in the species. The following describes several such enzymes. 

Biology and Chemistry of Jerusalem Artichoke Helianthus tuberosus L. 

Cinnamic acid hydroxylase Cyclic AMP phosphodiesterase Diamine oxidase 

Park et al., 1991 Zawistowski et al., 1988a, 1988b, 1987a, 1987b 

The downstream synthesis of two coumarins, ayapin (6,7-methylenedioxy-coumarin) and sco-poletin (6-methoxy-7-hydroxy-coumarin), is of biological interest due to their apparent roles as phytoalexins. Their accumulation has been correlated with resistance to pathogens in Helianthus (Tal and Robeson, 1986a, 1986b) and as feeding deterrents (Olson and Roseland, 1991). Both compounds are found in Jerusalem artichoke tubers (Cabello-Hurtado et al., 1998), and their synthesis via the phenylpropanoid pathway involves the first three steps leading to the activation of 4-coumaroyl CoA (Werck-Reichhart, 1995). Several routes have been postulated ayapin does not appear to be derived from scopoletin (Cabello-Hurtado et al., 1998). 

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In chickens a pattern similar to a capacity limited-elimination was noticed. The cause may be either a capacity limitation in the SDM metabolism (hydroxylation ) of SDM or extensive drug reabsorption from the cloaca occurring at night(known as chrono-pharma-cokinetics). In the chicken, 58 % of the intravenously administered dose is lost, which is also reported for other birds (24). Thus birds must possess additional metabolic pathways. 

A full characterization of the metabolic pathways of CPT-11 in human cancer patients has not been undertaken. The incomplete recovery of the irinotecan dose based on urine and bile determinations of irinotecan, SN-38, and SN-38 glucuronide suggests the presence of additional unidentified metabolites. Recently, a major metabolite, 7-ethyl-10-[4-A-(5-aminopenatoic acid)-l-piperidino]carbonyloxycamptothecin, has been identified in dogs and humans, suggesting the presence of an additional metabolic pathway (18). Renal clearance has not been reported to be a major route of elimination for these compounds in humans. 

Three metabolic pathways were identified (i) O-dealkylation to metabolites Ml and M2, with subsequent glucuronidation to metabolites M3 and M5 (ii) hydrolysis to metabolite M4 and (iii) N-oxidation to metabolite M6 (Fig. 3.13). Additional metabolic pathways maybe operative, as represented by the number of unknown compounds observed. However, as each unknown metabolite represented an average of <2% of the dose, these pathways are considered minor contributors to the metabolic process [52],... 

One obvious way to treat pathogens that have accumulated multiple resistance mechanisms or are intrinsically resistant to a given therapy is to use a drug with an entirely different mode of action. Since the major antifungal therapies target sterol biosynthesis or composition, a large variety of additional metabolic pathways are theoretically available. In reality,... 

In the rat studies a major additional metabolic pathway was discovered, which had not been found in soils, i.e. the hydroxylation of the intact diflubenzuron molecule leading to the three different metabolites indicated in the Figure, which were found partly as conjugates. These hydroxy derivatives accounted for almost all the metabolites in the bile and for about half the metabolites in the urine. The rat metabolism studies will be published more extensively elsewhere (22.) ... 

The field of solid phase synthesis has also benefited from enzyme technology. Several reports have described the use of sialyltransferases in the solid-supported synthesis of oligosaccharides that bear sialic acid [49]. Additionally, metabolic pathways have been harnessed by Bertozzi and coworkers to synthesize glycoconjugates on cell surfaces that bear modihed sialic acids [50]. 

Some plants possess an additional metabolic pathway to concentrate carbon dioxide before it enters the Calvin cycle. These are called C4 plants because of the 4-carbon molecules that are formed as intermediates. C4 plants comprise about 1% of plant species and 5% of the Earth s plant biomass. They have higher photosynthetic efficiency than do C3 plants. C4 plants are found in habitats with high daytime temperatures and intense sunlight. They also have an advantage in dry climates because their leaf stomata do not have to be as open to admit CO2 as those for C3 plants. Open stomata allow loss of water to the atmosphere. 

The use of foods by organisms is termed nutrition. The ability of an organism to use a particular food material depends upon its chemical composition and upon the metabolic pathways available to the organism. In addition to essential fiber, food includes the macronutrients—protein, carbohydrate, and lipid—and the micronutrients—including vitamins and minerals. 

Biochemistry is carbonyl chemistiy. Almost all metabolic pathways used by living organisms involve one or more of the four fundamental carbonvl-group reactions we ve seen in Chapters 19 through 23. The digestion and metabolic breakdown of all the major classes of food molecules—fats, carbohydrates, and proteins—take place by nucleophilic addition reactions, nucleophilic acyl substitutions, a substitutions, and carbonyl condensations. Similarly, hormones and other crucial biological molecules are built up from smaller precursors by these same carbonyl-group reactions. 

The NHase responsible for aldoxime metabolism from the i -pyridine-3-aldoxime-degrading bacterium, Rhodococcus sp. strain YH3-3, was purified and characterized. Addition of cobalt ion was necessary for the formation of enzyme. The native enzyme had a Mr of 130000 and consisted of two subunits (a-subunit, 27 100 (3-subunit, 34500). The enzyme contained approximately 2 mol cobalt per mol enzyme. The enzyme had a wide substrate specificity it acted on aliphatic saturated and unsaturated as well as aromatic nitriles. The N-terminus of the (3-subunit showed good sequence similarities with those of other NHases. Thus, this NHase is part of the metabolic pathway for aldoximes in microorganisms. 

The assessment of clearance is complicated by the numerous mechanisms by which compounds may be cleared from the body. These mechanisms include oxidative metabolism, most commonly by CYP enzymes, but also in some cases by other enzymes including but not limited to monoamine oxidases (MAO), flavin-containing monooxygenases (FMO), and aldehyde oxidase [45, 46], Non-oxidative metabolism such as conjugation or hydrolysis may be effected by enzymes such as glucuronyl transferases (UGT), glutathione transferases (GST), amidases, esterases, or ketone reductases, as well as other enzymes [47, 48], In addition to metabolic pathways, parent compound may be excreted directly via passive or active transport processes, most commonly into the urine or bile. 

Skeletal muscle uses only ATP as a source of energy for contraction. However, intracellular stores of ATP are quite limited. In fact, the amount of ATP normally found in skeletal muscle is enough to sustain only a few seconds of contraction. Therefore, metabolic pathways to form additional ATP are needed. These pathways include ... 

Assuming that the metabolic pathways are similar in the biosynthesis of related isocyanoterpenes, these studies remain difficult, due in part to the competitive formation of other secondary metabolites. In addition to the common trio (-NC, NCS, -NHCHO) of the nitrogenous functions found attached to these skeletons, analogs such as -CN, -CNO, and -SCN foreshadow the complexity of identifying and selecting specific precursors to be targeted for incorporation into the family of marine isonitriles. 

In addition, it has been discovered that there are naturally occurring enzymes that facilitate Diels-Alder type reactions within certain metabolic pathways and that enzymes are also instrumental in forming polyketides, isoprenoids, phenylpropanoids, and alkaloids (de Araujo et al., 2006). Agresti et al. (2005) identified ribozymes from RNA oligo libraries that catalyzed multiple-turnover Diels-Alder cycloaddition reactions. 

Plants produce an amazing diversity of secondary metabolites that not only play important biological roles in their adaptation to environments but also provide humans with dyes, flavors, drugs, fragrance, and other useful chemicals. However, many of the secondary metabolic pathways are found or are amplified only in limited taxonomic groups. In addition, the compounds are often restricted to a particular... 

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