Studies on metabolism

E2. Eisenberg, F., Isselbacher, K. J., and Kalckar, H. M., Studies on metabolism of carbon-14-labelled galactose in a galactosemie individual. Science 125, 116-117 (1957). 

T. Watabe, N. Ozawa, A. Hiratsuka, Studies on Metabolism and Toxicity of Styrene. VI. Regioselectivity in Glutathione 5-Conjugation and Hydrolysis of Racemic, R- and S-Phenyloxiranes in Rat Liver , Biochem. Pharmacol. 1983, 32, 111 - 785. 

Prueksaritanont T, Zhao JJ, Ma B, et al. Mechanistic studies on metabolic interactions between gemfibrozil and statins. Pharmacol Exp Ther 2002 301(3) 1042-1051. 

Mertz DP, Wilk G, Koschnick R. 1975. [Conditions affecting renal excretion of silver by humans. Studies on metabolism of trace elements. VIII]. Z Klin Chem Klin Biochem 13 13-15. (German). 

Italian physician Santorio Santorio (1561-1636) publishes studies on metabolism. 

Particular attention is given to the D-Roms test (14), which is very simple and has been used also to evaluate the antioxidant activity of some products in patients and healthy subjects. The test is based on the determination of hydroperoxides that are derivatives of oxidized lipids and consequently indicate the OS at cellular level. The test is used for the epidemiological study on metabolic syndrome, in Italy by the European Society of Biological Nutrition. 

Domanski T, Trojanowska B. 1980. Studies on metabolic kinetics of lead and alkaline earth elements (Ca, Ba). Acta Physiol Pol 31 439-447. 

Kohen, E., Thorell, B., Kohen, C. and Salmon, J.-M. Studies on metabolic events in localized compartments... 

Two-dimensional planar chromatography (2D-TLC) is frequently used in combination with autoradiography or digital autoradiography (DAR) in studies on metabolism. Examples of 2D-TLC-DAR will be given in the analysis of pharmaceutical products. Other applications generally use either different types of development, or utilise different interactions for separation, or different stationary phases, such as elution-displacement absorption-partition normal phase-reversed phase ion exchange-normal phase. 

Experiences in cat nutrition underscore the fallacy of assuming that metabolic pathways found in one species are automatically present in others. Early studies on metabolism of PUFA were conducted on rats, which have high A6 and A5 desa-turase abilities to convert linoleic acid (18 2n-6) to the prostaglandin precursors dihomo-y-linolenic acid (20 3 -6) and arachidonic acid (20 4 -6), respectively. This led to the assumption that other species can desaturate polyunsaturated fatty acids equally well. Over a period of time, it was shown that cats are not able to convert 18 2 -6 to 20 3n-6 or 20 4 -6. The NRC currently recommends the inclusion of 5 g linoleic acid and 0.2 g arachidonic acid/kg diet dry matter. 

Since it is the smallest aromatic hydrocarbon to have a bay-region and a K-region , phenanthrene is often used as a model substrate for studies on metabolism of carcinogenic PAHs. Phenanthrene is absorbed following oral and dermal exposure. Data from structurally related PAHs suggest that phenanthrene would be absorbed from the lungs. Metabolites of phenanthrene identified in in vivo and in vitro studies indicate that metabolism proceeds by epoxidation at the 1-2, 3-4, and 9-10 carbons, with dihydrodiols as the primary metabolites. 

Shift reagents have not been used extensively in xenobiotic metabolism studies however, they may find increased use for determination of isomer composition in studies on metabolic mechanisms because metabolic rates are often different for geometric and stereoisomers. Mizugaki et al. used NMR with Eu(fod)3 to determine structures of cis- and trans-3-alkenoic acids (22). Moser et al. used NK and a chiral shift reagent for analysis of the... 

Gavaghan, C.L. Nicholson, J.K. Connor, S.C. Wilson, I.D. Wright, B. Holmes, E. HPLC-NMR Spectroscopic and Chemometric Studies on Metabolic Variation in Sprague Dawley Rats, Anal. Biochem. 291 (2), 245-252 (2001). 

Koga N, Beppu M, Ishida C, et al. 1989. Further studies on metabolism in vivo of 3,4,3, 4 -tetrachlorobiphenyl in rats identification of minor metabolites in rat feces. Xenobiotica... 

R3. Rao, K. S., Sastry, P. S., and Ganguly, J., Studies on metabolism of vitamin A. 2. Enzymic synthesis and hydrolysis of phenolic sulphates in vitamin-A-defident rats. Biochem. J. 87,312-317 (1963). 

Studies on metabolic stability using hepatocyte suspensions are not feasible for automation/HTS, but these studies do provide rather complete profiles of hepatic biotransformation without the supplements of cofactors and cosubstrates. The use of S9 in metabolic stability studies can be evaluated in a manner similar to that used for the microsomal assays, but with the possible addition of a broader panel of cofactors or cosubstrates. These include NADPH for CYP/FMO-mediated reactions, NADH for xanthine oxidoreductase and quinone oxidoreductase 2, NADPH-dependent reductions by carbonyl reductases, and NADPH/NADH-dependent reductions catalyzed by aldo-keto reductases, uridine 5 -diphosphate... 

Yoshida, H. Kohno, Y. Endo, H. Yamaguchi, J. Fukushima, K. Suwa, T. Hayashi, M. Mechanistic studies on metabolic chiral inversion of 4-(4-methylphenyl)-2-methylthiomethyl-4-oxobutanoic acid (KE-748), an active metabolite of the new anti-rheumatic agent 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298), in rats. Biochem. Pharmacol. 1997, 53, 179-187. 

Before a new type of food surfactant is permitted for use by the health authorities it has to be tested in a number of toxicological studies including short-term and long-term feeding trials on several species together with studies on metabolism. (WHO, 1974). 

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