Metabolism of Alcohols
Ronald R. Scheline in Handbook of Mammalian Metabolism of Plant Compounds (1991), 1991
Two main metabolic pathways are available for alcohols: oxidation and direct conjugation. The oxidation of alcohols is carried out by enzymes designated oxidoreductases. In contrast to many oxidative reactions which are catalyzed by NADPH-dependent monooxygenases located in the endoplasmatic reticulum, alcohol oxidation is to a large extent carried out by soluble liver enzymes. The best known of these is liver alcohol dehydrogenase which has been studied mainly in connection with its role in ethanol metabolism, however it is also responsible for the oxidation of many xenobiotic alcohols of various types. The general reaction shown by primary alcohols is: It is noteworthy that this reaction is reversible, allowing both aldehydes and ketones to be reduced. Since the reaction is pH-dependent, in vitro systems show a shift in the equilibrium to the carbinol form as the pH is lowered to neutrality. However, the formation of the aldehydes is usually favored in vivo because these products can be further oxidized to acids.
Metabolism of Higher Terpenoids
Ronald R. Scheline in Handbook of Mammalian Metabolism of Plant Compounds (1991), 1991
Terpenoid compounds include a multitude of diverse plant constituents which are related by virtue of a common biosynthetic origin. Thus, their basic skeletons are derived from mevalonic acid and consist of C5-units, i.e., the isoprene molecule (CH2=C(CH3)-CH=CH2). They are further classified according to the number of such units present, the simplest C 10-derivatives containing two. These C 10-compounds are known as monoterpenoids and in this book the choice was made to include them in other chapters rather than with their higher relatives. This decision was dictated by their close metabolic relationship to other classes of plant compounds, especially the alcohols, aldehydes, and ketones, and, in contrast, the lack of similarity to the metabolism seen with many of the terpenoids included in this chapter. These latter compounds include the sesquiterpenoids (C I5), diterpenoids (C20), triterpenoids (C30), and tetraterpenoids (C40).
Why eat?
David A. Bender in Introduction to Nutrition and Metabolism, 2002
An adult eats about a tonne of food a year. This book attempts to answer the question ‘why?’ – by exploring the need for food and the uses to which that food is put in the body. Some discussion of chemistry and biochemistry is obviously essential in order to investigate the fate of food in the body, and why there is a continuous need for food throughout life. Therefore, in the following chapters various aspects of biochemistry and metabolism will be discussed. This should provide not only the basis of our present understanding, knowledge and concepts in nutrition, but also, more importantly, a basis from which to interpret future research findings and evaluate new ideas and hypotheses as they are formulated.
NADPH-, NADH- and cumene hydroperoxide-dependent metabolism of benzo[a]pyrene by pyloric caeca microsomes of the sea star
Published in Xenobiotica, 1994
P. J. Den Besten, P. Lemaire, D. R. Livingstone
1. Benzo[a]pyrene (BaP) metabolism was studied in microsomes of the pyloric caeca (main digestive tissue and site of P450) of the echinoderm sea star (starfish) Asterias rubens. 2. NADPH-dependent metabolism of BaP produced phenols (36% of total metabolism), quinones (19%), dihydrodiols (25%) and putative protein adducts (20%). 3. NADH-dependent rates of BaP metabolism were approximately twice those found for NADPH-dependent metabolism, and metabolite formation was shifted towards dihydrodiols and quinones. 4. Cumene hydroperoxide (CHP)-dependent rates of BaP metabolism were also higher than NADPH-dependent rates by a factor of six for quinone and putative protein adduct production, and by a factor of four for phenol and dihydrodiol production. 5. Microsomal rates of BaP metabolism in BaP-exposed sea stars appeared to be elevated more in the case of NADPH-dependent than for CHP-dependent metabolism (respectively, increases of 130 and 41%), indicating the induction of forms of P450 preferentially catalysing NADPH-dependent metabolism. 6. 1,1,1-Trichloropropene-2,3-oxide (TCPO) inhibited dihydrodiol formation from both NADPH- and CHP-dependent BaP metabolism, indicating the involvement of epoxide hydratase in BaP metabolism. 7. Incubations of pyloric caeca microsomes with BaP and a superoxide anion radical-generating system (xanthine/xanthine oxidase) produced putative protein adducts but no free metabolites.
The Rate of Aniline Metabolism
Published in Xenobiotica, 1975
Justyna M. Wiśniewska-knypl, Janina K. Jabłońska
1. The rates of aniline metabolism have been studied in vitro using rat liver homogenates, and in vivo by determination of the unchanged aniline remaining in the cadaver. 2. Metabolism of aniline in vivo is stimulated by phenobarbital and 3,4-benzpyrene, and inhibited by SKF 525-A. 3. Cyclobarbital and phenacetin stimulate aniline metabolism both in vitro and in vivo. 4. Pre-treatment with aniline impaired the metabolism of aniline in vivo but increased the in vitro metabolism to p-aminophenol. Pre-treatment of rats with phenobarbital and aniline did not accelerate metabolism of aniline in vivo but the stimulating effect of phenobarbital on protein synthesis in microsomes was maintained. In contrast, pre-treatment with 3,4-benzpyrene and aniline stimulated metabolism of aniline in vivo. The possible mechanism of changes in aniline metabolism due to previous exposure to aniline is discussed.
Species difference in stereoselective involvement of CYP3A in the mono-
Published in Xenobiotica, 2001
L. Zhang, J. F. Fitzloff, L. C. Engel, C. S. Cook
1. To determine which CYP isoenzyme is involved in the N-dealkylation of disopyramide (DP) metabolism in human and dog, and to determine the stereoselectivity of DP metabolism with human CYP and dog CYP isoenzymes, the following in vitro metabolism studies of DP were conducted: correlation between human CYP isoenzyme activities and DP metabolism with human liver microsomes; inhibition of DP metabolism in human and dog liver microsomes with chemical inhibitors of CYP isoenzymes; inhibition of DP metabolism inhuman microsomes withhuman CYPantibodies; inhibition of DP metabolism in dog liver microsomes with human and dog CYP antibodies; metabolism of DP with human (CYP3A4) and dog (CYP3A12) cDNA-expressed isoenzymes; determination of Km and Vmax of DP enantiomers by using cDNA-expressed CYP3A4 and CYP3A12. 2. In human liver microsomes, the formation of the mono-N-dealkylated disopyramide (MNDP) metabolite was best correlated with CYP3A4 activities. DP metabolism was substantially inhibited by ketoconazole, troleandomycin (TA) and human CYP3A4 antibody. DP was metabolized by cDNA-expressed CYP3A isoenzymes. In dog liver microsomes, DP metabolism was inhibited by ketoconazole, TA and dog anti-CYP3A12. DP was also metabolized by cDNA-expressed CYP3A12. 3. CYP3A4 and CYP3A12 are the principal isoenzymes involved in DP metabolism in human and dog respectively. There was no stereoselectivity in N-dealkylation of DP by human CYP3A4. However, there was notable stereoselectivity in the N-dealkylation by dog CYP3A12.
Related Knowledge Centers
- Anabolism
- Cellular Respiration
- Catabolism
- Adenosine Triphosphate