Mechanisms of Oxygen Metabolism

Mason, Howard S.

doi:10.1002/9780470122648.ch2

Cited by 83 publications

(16 citation statements)

References 560 publications

(76 reference statements)

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“…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 carcinogens (Mueller and Miller) [9].…”

Section: Discovery and Purificationmentioning

confidence: 99%

“…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 carcinogens (Mueller and Miller) [9].…”

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confidence: 99%

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

Furge

Guengerich

2006

Biochem Molecular Bio Educ

144

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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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Section: Discovery and Purificationmentioning

confidence: 99%

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confidence: 99%

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

Furge

Guengerich

2006

Biochem Molecular Bio Educ

144

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“…However, 2,3-DHBA was preferentially formed because Fe 2+ can either react with the OH groups of the molecule or form a ferryl ion, which interacts with the hydroxyl substrate, often giving a complex. Mason et al (1957) On the other hand, Groves et al (1974;1976) have used this mechanism to describe the hydroxylation of cyclohexanol, which is strongly supported by the formation of stereoselective hydroxylation products. These interactions have also been observed by Lunak et al (1994) and Lang et al (1994) during the photochemical hydroxylation of 2-HBA, where the formation of 2,3-DHBA was favored.…”

Section: +mentioning

confidence: 95%

Degradation of 2-hydroxybenzoic acid by advanced oxidation processes

Zanta

Martínez‐Huitle

2009

Braz. J. Chem. Eng.

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-In this study, advanced oxidation processes (AOPs) such as the UV/H 2 O 2 and Fenton processes were investigated for the degradation of 2-hydroxybenzoic acid (2-HBA) in lab-scale experiments. Different [H 2 O 2 ]/[2-HBA] molar ratios and pH values were used in order to establish the most favorable experimental conditions for the Fenton process. For comparison purposes, degradation of 2-HBA was carried out by the UV/H 2 O 2 process under Fenton experimental conditions. The study showed that the Fenton process (a mixture of hydrogen peroxide and Fe 2+ ion) was the most effective under acidic conditions, leading to the highest rate of 2-hydroxybenzoic acid degradation in a very short time interval. This same process led to a six-fold acceleration of the oxidation rate compared with the UV/H 2 O 2 process. The degradation of 2-hydroxybenzoic acid was found to follow first-order kinetics and to be influenced by the type of process and the experimental conditions. The experimental results showed that the most favorable conditions for 2-HBA degradation by the

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“…They characterized the reaction as belonging to the class of enzymes categorized by Mason as "mixed-function oxidases" (Mason, 1957) and by Hayaishi as "oxygenases" (Hayaishi, 1962). These enzymes required molecular oxygen and a reductant such as NADPH.…”

Section: Discovery Of P450mentioning

confidence: 99%

The Development of Drug Metabolism Research as Expressed in the Publications of ASPET: Part 2, 1959–1983

Murphy¹

2008

Drug Metab Dispos

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ABSTRACT:In 25 years, drug metabolism research went from using subcellular particles of undefined content to an understanding of metabolism at the molecular level. The discoveries of cytochrome P450, enzyme induction, reactive intermediates, and genetic polymorphisms were milestones in the field. New publications from the American Society for Pharmacology and Experimental Therapeutics chronicled the discoveries and provided communications to advance the science of drug metabolism.

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Mechanisms of Oxygen Metabolism

Cited by 83 publications

References 560 publications

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

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

Degradation of 2-hydroxybenzoic acid by advanced oxidation processes

The Development of Drug Metabolism Research as Expressed in the Publications of ASPET: Part 2, 1959–1983

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