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Metabolism of Chemical Carcinogens by Intestinal Tissue
Published in Herman Autrup, Gary M. Williams, Experimental Colon Carcinogenesis, 2019
The small and large intestinal cytochrome P-450-dependent monooxygenase systems exhibit the same general reaction characteristics as the hepatic system, i.e., they are dependent on NADPH and O2, and inhibited by CO.32,33 Each monooxygenase system contains at least two catalytic components, namely NADPH-cytochrome P-450 reductase and cytochrome P-450. These monooxygenase components have been purified from rat large intestinal microsomes and phospholipid is required for metabolic activity upon reconstitution.34 Cytochrome P-450 has also been detected in mitochondria of the rat small intestine.35 Furthermore, fatty acid-dependent drug oxidation has been shown to be catalyzed by prostaglandin endoperoxide synthetase in rat and human colonic microsomes.36
Pharmacokinetics of Amphetamines: In Vivo and in Vitro Studies of Factors Governing Their Elimination
Published in John Caldwell, S. Joseph Mulé, Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects, 2019
Although from many studies it has become evident that more than one enzyme is involved in the microsomal oxidation of drugs, the multiplicity of the monooxygenase system is still the subject of much speculation. The existence of different types of cytochromes P-450 has been adequately demonstrated by the spectral studies of microsomal preparations63 and by studies on isolation and purification of cytochrome P-450 from 3-methylcholanthrene and phenobarbital treated rats.64–66 Strong evidence for the heterogeneity of this enzyme system also emerges from data on differential changes in the route or the rate of oxidation of selected substrates in the presence of inhibitors or after induction.67–69 Gram70 suggested in 1971 that the N-demethylation of secondary and tertiary amines proceeds via different N-demethylase systems. It is now accepted that secondary amines, like N-alkyl substituted amphetamines are partly metabolized by N-hydroxylation, whereas tertiary amines are processed by N-oxidation.43,52–56,71
Mammalian CYP2D Members A Comparison of Structure, Function, and Regulation
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
The CYP-dependent monooxygenase system has evolved as a multigene superfamily of proteins with the capacity to insert an atom of molecular oxygen into a substrate and to carry out a variety of other reactions. This property has been exploited through evolution to enable the CYP system to play a key role in xenobiotic and drug metabolism, metabolic homeostasis, and biosynthesis of endogenous compounds that play important physiological roles.
Pathogenic variants in the CYP21A2 gene cause isolated autosomal dominant congenital posterior polar cataracts
Published in Ophthalmic Genetics, 2022
Vanita Berry, Nikolas Pontikos, Alex Ionides, Angelos Kalitzeos, Roy A. Quinlan, Michel Michaelides
CYP21A2 is a member of the cytochrome P450 (CYP450) family of enzymes, and it is also known as steroid 21-hydroxylase, important in the biosynthesis of mineralocorticoids (aldosterone) and glucocorticoids (cortisol). Like other steroid hydroxyases, it requires a heme cofactor to function as a monooxygenase and catalyse the oxidization and hydroxylation of a variety of steroid substrates at position 21 (5), such as progesterone and 17α-hydroxyprogesterone, precursors in the synthesis of aldosterone and cortisol, respectively. For this reason, CYP21A2 is associated with CAH (6), an autosomal recessive endocrine disorder (7,8) that leads to aldosterone deficiency and in its severe form, the pathological loss of sodium ions (9). Here, for the first time, we have identified pathogenic variants in CYP21A2 gene causing an isolated autosomal dominant posterior polar congenital cataract.
Renal and Hepatic Disease: Cnidoscolus aconitifolius as Diet Therapy Proposal for Prevention and Treatment
Published in Journal of the American College of Nutrition, 2021
Maria Lilibeth Manzanilla Valdez, Maira Rubi Segura Campos
In order to excrete non-soluble drugs, xenobiotics of metabolites, these must be metabolized in the liver. Both drugs and fat-soluble chemicals are transported into plasma through proteins to the liver, in order to convert them into water-soluble molecules and be able to eliminate by the kidney (14). These enzymes are responsible for oxidizing, reducing, hydrolyzing, or methylation process. This is achieved with three different phases:Drug oxidation; the CYP monooxygenases contain oxidation and reduction enzymes. These reactions take place in the cytochrome P450. Monooxygenases metabolize substrates by incorporating an oxygen atom of O2 molecules and form –OH.Conjugation reaction: includes sulfation, methylation, and glucuronidation, these reactions in order to increase the solubility of the metabolites.Drug transporters: these, takes the metabolites into the membranes of hepatocytes, kidney and intestine cells for excretion. The liver can also excrete some hormones such as thyroxine, estrogen, cortisol, and aldosterone.
Irreversible oxidative post-translational modifications in heart disease
Published in Expert Review of Proteomics, 2019
Tamara Tomin, Matthias Schittmayer, Sophie Honeder, Christoph Heininger, Ruth Birner-Gruenberger
Finally, irreversible oxidations also affect amino acids with aromatic side chains (Figure 1). Oxidation of aromatic amino acids can either take place in an enzyme-catalyzed manner, e.g. by monooxygenases and peroxidases, or via free hydroxyl radicals. While oxidation of phenylalanine yields tyrosine, further oxidation can either lead to the formation of protein-dihydroxyphenylalanine or to a di-tyrosine crosslink. Tryptophan can be oxidized to kynurenine via two intermediate steps by tryptophan dioxygenase or to 5-hydroxytryptophan via the serotonin biosynthesis pathway whereas random hydroxylations at various positions can occur in the presence of hydroxyl radicals [72,73]. A list of recent publications investigating irreversible oxidative modifications in the cardiovascular field is shown in Table 2.