Photochemical Action Spectrum of the Terminal Oxidase of Mixed Function Oxidase Systems

Cooper, David Y.; Levin, Scott; Narasimhulu, Shakunthala; Rosenthal, Otto; Estabrook, Ronald W.

doi:10.1126/science.147.3656.400

Cited by 479 publications

(104 citation statements)

References 9 publications

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“…Moreover, it was recently shown that the administration of phenobarbital markedly stimulate amount of P-450 and other several lines of evidence indicate that P-450 may have an important role for the oxidation of drugs in liver microsomes (21)(22)(23)(24)(25). Therefore, it was of interest to see whether the alternations in the amount of cytochrome b5 and P-450 by the treatment with phenobarbital or methylcholanthrene in the starved or sucrose fed rats were parallel to these in the activities of drug-metabolizing enzymes and NADPH-dependent electron transfer system.…”

Section: Methodsmentioning

confidence: 99%

Effect of Phenobarbital Treatment on the Activities of Nadph-Dependent Enzymes of Liver Microsomes in Fasted or Sucrose Fed Rats

Kato

1967

Jpn.J.Pharmacol

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It is well documented that the activities of many microsomal enzymes which meta bolize foreign compounds are markedly stimulated by administration of phenobarbital and other drugs. The mechanism of the increased activity of these enzymes is likely due to de novo synthesis of microsomal enzymes (1-4).In a previous communication the author reported a marked increae in the activities of N-demethylation of aminopyrine and hydroxylation of aniline in liver microsomes of fasted female rats (5).On the other hand, recently Pitot and Peraino (6) reported that the administration of glucose suppressed the induction of threonine dehydrase after the forced feeding with casein hydrate.It is therefore interesting to investigate a possible interaction in the increase in activities of some microsomal NADPH-dependent enzymes between phenobarbital treatment and starvation or sucrose feeding.The results reported here indicated that the activities of NADPH-dependent enzymes are increased or not altered by starvation, however these activities are markedly depressed by sucrose feeding.Moreover, the stimulation of the activities of the microsomal enzymes by phenobar bital was not prevented in the sucrose fed female rats and indeed the phenobarbital effect was potentiated in the fasted female rats. METHODSFemale and male rats of Sprague-Dawley strain, weighing about 160 and 180g, respec tively, were used. The rats were divided in three groups, and fed on standard chow diet or sucrose, or fasted for 72 hours. Halves of the each group were treated with phenobar bital sodium (80 mg/kg) or methylcholanthrene (40 mg/kg) 72 hours and 48 hours before the sacrifice.

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Section: Methodsmentioning

confidence: 99%

Effect of Phenobarbital Treatment on the Activities of Nadph-Dependent Enzymes of Liver Microsomes in Fasted or Sucrose Fed Rats

Kato

1967

Jpn.J.Pharmacol

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“…A role of P450 in steroid hydroxylation was established by D. Cooper et al [14], and the work was carried over to other substrates. A major advance in the study of these mixed-function oxidase reactions occurred in the 1960s with the discovery of a soluble (non-membrane-bound) P450 from the bacterium Pseudomonas putida by I. Gunsalus and co-workers [15].…”

Section: Discovery and Purificationmentioning

confidence: 99%

Cytochrome P450 enzymes in drug metabolism and chemical toxicology: An introduction

Furge

Guengerich

2006

Biochem Molecular Bio Educ

143

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Cytochrome P450 (P450) enzymes include a family of related enzymes that are involved in metabolism of vitamins, steroids, fatty acids, and other chemicals. This review presents a brief historical overview of the discovery and characterization of P450 enzymes extending from intermediary metabolism to the fields of drug metabolism and toxicology. Introductions to P450 enzyme structure and function are also presented. The goals of this review are to 1) provide an introduction to a few of the many aspects of P450 research relating to humans, 2) introduce additional ways of thinking about metabolism, 3) provide some basic examples of P450 enzymology, and 4) provide applications to topics widely taught in undergraduate courses in biochemistry.Keywords: Cytochrome P450 enzyme, drug metabolism, chemical toxicity, P450 mechanism.Cytochrome P450 (P450) 1 enzymes are a family of heme-containing proteins found from bacteria to human. In mammals, the enzymes are membrane-bound (usually in the endoplasmic reticulum, although the seven in Families 11, 24, and 27 are found in mitochondria; Table I). P450s serve a variety of functions including steroid, fatty acid, eicosanoid, and vitamin A and D metabolism as well as metabolism of foreign compounds including natural products, pharmaceuticals, and carcinogens. P450s are found in every tissue except skeletal muscle and red blood cells [1]. With the completion of the human genome sequence project, there appear to be 57 distinct P450 genes in humans [2]. Of these, about 13 are "orphan" P450s for which the metabolic function is not yet known [3].There is wide interest in P450s due to applications in a variety of fields including biochemistry, biotechnology, chemistry, environmental sciences, enzymology, microbiology, physiology, pharmacology, plant sciences, and toxicology. Indeed, in the last decade alone, there were more than 1000 publications per year relating to P450s. This review will highlight the roles of human P450s in drug metabolism and chemical toxicity and applications to undergraduate studies. References to more in-depth reviews are also provided. DISCOVERY AND PURIFICATIONThe history of P450 can be traced back to questions related to the metabolism of steroids, drugs, and carcinogens in the 1940s. Early studies of difficult alkyl oxidations of amino acids and fatty acids, such as oxidation at the terminal methyl group of a fatty acid, allowed for the isolation of cell-free extracts capable of performing NAD(P)Hdependent oxidation reactions [4]. The "mixed-function oxidase" stoichiometry.that is now recognized as the basic reaction catalyzed by a P450 was not immediately obvious. In particular, the requirement for a reduced pyridine nucleotide to achieve an overall oxidation was surprising at the time. The concept of mixed-function oxidation was developed by O. Hayaishi et al. in Japan [5] and H. Mason in the U.S [6]. Subsequently, such reactions were shown to occur with steroids and xenobiotics, particularly drugs (J. Axelrod and B. Brodie et al.) [7,8] and carcinogen...

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“…Nonetheless, we considered that pharmacogenomic labeling was not possible at approval for CYP450s and drugs approved before the seminal article of Cooper et al, which was published in 1965. 12 Similarly, for glucose-6-phosphate dehydrogenase, we considered that pharmacogenomic labeling was not present at approval for drugs approved before the publication by Alving and colleagues in 1956. 13 …”

Section: Data Extractionmentioning

confidence: 99%

Guidance for pharmacogenomic biomarker testing in labels of FDA-approved drugs

Vivot

Boutron

Ravaud

et al. 2015

Genetics in Medicine

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Photochemical Action Spectrum of the Terminal Oxidase of Mixed Function Oxidase Systems

Cited by 479 publications

References 9 publications

Effect of Phenobarbital Treatment on the Activities of Nadph-Dependent Enzymes of Liver Microsomes in Fasted or Sucrose Fed Rats

Effect of Phenobarbital Treatment on the Activities of Nadph-Dependent Enzymes of Liver Microsomes in Fasted or Sucrose Fed Rats

Cytochrome P450 enzymes in drug metabolism and chemical toxicology: An introduction

Guidance for pharmacogenomic biomarker testing in labels of FDA-approved drugs

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