Consequences of psychophysiological stress on cytochrome P450-catalyzed drug metabolism

Konstandi, Maria; Johnson, Elizabeth O.; Lang, Matti A.

doi:10.1016/j.neubiorev.2014.05.011

Cited by 41 publications

(78 citation statements)

References 215 publications

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“…The P450s are arranged in families based on sequence homologies (340,342) and are very versatile catalysts that activate dioxygen and insert a single oxygen atom into almost any organic compound imaginable (255). Cytochrome P450s are a family of heme-containing monooxygenases that are involved in the oxidation of ethanol, methanol, steroids, fatty acids, and numerous xenobiotics (acetone, benzene, and other alcohols) ingested from the environment (62,249,252,295,530). The heme iron of the CYP enzymes binds two oxygen atoms.…”

Section: Cytochrome P450s-mediated Oxidation Of Methanol and Ethanolmentioning

confidence: 99%

“…Most P450s are considered to operate according to a general scheme (FIGURE 6) (26,27,86,508). There are many P450 isoforms encoded by more than 100 gene families (249,252,340,342,530,538). P450 functions in conjunction with microsomal enzymes such as NADPH-cytochrome P450 reductase and cytochrome b 5 (342) (FIGURE 6).…”

Section: Cytochrome P450s-mediated Oxidation Of Methanol and Ethanolmentioning

confidence: 99%

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Metabolic Methanol: Molecular Pathways and Physiological Roles

Dorokhov

Shindyapina

Sheshukova

et al. 2015

Physiological Reviews

165

125

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Methanol has been historically considered an exogenous product that leads only to pathological changes in the human body when consumed. However, in normal, healthy individuals, methanol and its short-lived oxidized product, formaldehyde, are naturally occurring compounds whose functions and origins have received limited attention. There are several sources of human physiological methanol. Fruits, vegetables, and alcoholic beverages are likely the main sources of exogenous methanol in the healthy human body. Metabolic methanol may occur as a result of fermentation by gut bacteria and metabolic processes involving S-adenosyl methionine. Regardless of its source, low levels of methanol in the body are maintained by physiological and metabolic clearance mechanisms. Although human blood contains small amounts of methanol and formaldehyde, the content of these molecules increases sharply after receiving even methanol-free ethanol, indicating an endogenous source of the metabolic methanol present at low levels in the blood regulated by a cluster of genes. Recent studies of the pathogenesis of neurological disorders indicate metabolic formaldehyde as a putative causative agent. The detection of increased formaldehyde content in the blood of both neurological patients and the elderly indicates the important role of genetic and biochemical mechanisms of maintaining low levels of methanol and formaldehyde.

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Section: Cytochrome P450s-mediated Oxidation Of Methanol and Ethanolmentioning

confidence: 99%

Section: Cytochrome P450s-mediated Oxidation Of Methanol and Ethanolmentioning

confidence: 99%

Metabolic Methanol: Molecular Pathways and Physiological Roles

Dorokhov

Shindyapina

Sheshukova

et al. 2015

Physiological Reviews

165

125

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“…Thus, the toxicity and the ratios of metabolites formed of B[ a ]P in vitro might be different depending of the experimental model and the procedure used, and in vivo product distribution might depend on exposure of an organism to variety of environmental impacts, as well as to its physiological state ( e.g. illness, stress) [7,8,32,33]. …”

Section: Discussionmentioning

confidence: 99%

Development and Uses of Offline and Web-Searchable Metabolism Databases - The Case of Benzo[a]pyrene

Rendić¹,

Guengerich

2018

CDM

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The present work describes development and use of offline and Web-searchable human and other species metabolism databases. A search of the databases presented will produce basic information on metabolic reactions or transporter systems published on specific drug or other chemical, kinetic values, as well as structure of the metabolites. In addition, searching enables comparison of the data between different species models. The data cover time the period until 2008, and the current Web-searchable database [19] is updated quarterly each year and over the period until October 2017. Users of the databases might find occasional discrepancies between the data searched, e.g. data on metabolic activations as presented in Table 6. This is because the data were collected from different literature sources over the time of collection. The data searched may find their application in prediction and interpretation of the metabolism of drugs and other chemicals, drug design, and development, as well as in clinical and toxicological studies. Application of data searching to the study of xeno- or endobiotics metabolism is illustrated by those searched for the properties of the known environmental carcinogens benzo[a]pyrene (B[a]P) and its metabolites covering the period until the year 2008. The results of the data analysis show higher activity of P450 1A1 for metabolic activation of the (−)- isomer, while P4501B1 exerts higher activity for the (+)- isomer of trans-7, 8-dihydroxy-7,8-dihydrobenzo[a]pyrene (trans-B[a]P-7,8-diol). P450 1A2 showed equally low activity in the metabolic activation of both isomers (Tables 2 and 3). The current Web-searchable metabolism database contains 125,359 entries.

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“…Moreover, CYP2B isozymes can be induced by GCs in liver. Variations in GC concentrations are another critical factor that either upregulates or downregulates CYP: CYP2A and CYP2C are induced at low GC concentrations but inhibited at high GC concentrations [ 39 ].…”

Section: Pharmacokinetic Interactionsmentioning

confidence: 99%