Molecular Mechanisms of Oxygen Activation reviews some of the major advances that have been made in our understanding of the molecular mechanisms underlying oxygen activation, with emphasis on the role of oxygen activation in contemporary biological processes. The biological role of oxygenases in the metabolism of fatty acids and steroids is discussed, along with the functions of heme-containing dioxygenases, a-ketoglutarate-coupled dioxygenases, and pterin-requiring aromatic amino acid hydroxylases. This book is comprised of 14 chapters and begins with an overview of the general properties and biological functions of oxygenases, along with the chemical aspects of oxygen fixation reactions. The reader is then introduced to research concerning fatty acid and steroid oxygenases which has appeared in the literature since 1962, paying particular attention to the mechanism of oxygenation and the biosynthesis and metabolism of steroids. Subsequent chapters explore the biological functions of a variety of oxygenases such as heme-containing dioxygenases, copper-containing oxygenases, flavoprotein oxygenases, and pterin-requiring aromatic amino acid hydroxylases. Superoxide dismutase, cytochrome c oxidase, peroxidase, and bacterial monoxygenases are also considered. This monograph should serve as a valuable reference for biochemists as well as undergraduate and graduate students of biochemistry.

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This monograph consists of manuscripts, summary statements, and poster abstracts submitted by invited speakers and poster contributors who participated in the symposium "Oxygen Complexes and Oxygen Activation by Transition Metals," held March 23-26, 1987, at Texas A&M University. This meeting was the fifth annual international symposium sponsored by the Texas A&M Industry-University Cooperative Chemistry Program (IUCCP). The co chairmen of the conference were Professors Arthur E. Martell and Donald T. Sawyer of the Texas A&M University Chemistry Department. The program was developed by an academic-industrial steering committee consisting of the co-chairmen and members appointed by the sponsoring chemical companies Dr. James F. Bradzil, The Standard Oil Company, Ohio; Dr. Jerry R. Ebner, Monsanto Company; Dr. Craig Murchison, Dow Chemical Company; Dr. Donald C. Olsen, Shell Development Company; Dr. Tim R. Ryan, Celanese Chemical Company; and Dr. Ron Sanderson, Texaco Chemical Company. The subject of this conference reflects the intense interest that has developed in academic institutions and industry on several aspects of dioxygen chemistry. These include the formation of dioxygen complexes and their applications in facilitated transport and oxygen separation; homo geneous and heterogeneous catalysis of oxidation; and oxygenation of organic substrates by molecular oxygen. The conference differs in two respects from several other symposia on dioxygen chemistry held during the past few years. First, there is extensive industrial participation, especially with respect to oxygen activation.

The aromatic amino acid hydroxylases phenylalanine hydroxylase (PheH), tyrosine hydroxylase (TyrH) and tryptophan hydroxylase (TrpH) utilize tetrahydropterin and molecular oxygen to catalyze aromatic hydroxylation. All three enzymes have similar active sites and contain an iron atom facially coordinated by two histidines and a glutamate. The three enzymes also catalyze the benzylic hydroxylation of 4- methylphenylalanine. The intrinsic primary and?-secondary isotope effects for benzylic hydroxylation and their temperature dependences are nearly identical for the three enzymes, suggesting that the transition states, the tunneling contributions and the reactivities of the iron centers are the same. When molecular oxygen and the tetrahydropterin are replaced by hydrogen peroxide (H2O2), these enzymes catalyze the hydroxylation of phenylalanine to form tyrosine and meta-tyrosine with nearly identical second order rate constants. When the H2O2-dependent reaction is carried out with cyclohexylalanine or 4-methylphenylalanine, the products are 4-HO-cyclohexylalanine and 4-hydroxymethylphenylalanine, respectively. These experiments provide further evidence that the intrinsic reactivities of the iron centers in these enzymes are the same. Wild-type PheH and the uncoupled mutant protein V379D exhibit normal and inverse isotope effects, respectively, with deuterated phenylalanines. When the reaction is monitored by stopped-flow absorbance spectroscopy, three steps are visible. The first step is the reversible binding of O2, the second step is 5-7 fold faster than the turnover number, setting a limiting value for the rate constant for O2 activation, and the last step is non-enzymatic. There is no burst in the pre-steady state formation of tyrosine. These results are consistent with formation of the new C-O bond to form tyrosine as the ratelimiting step of the reaction. The reaction of TrpH with both tryptophan and phenylalanine was studied by stopped-flow absorbance spectroscopy and rapid-quench product analysis. With either amino acid as substrate, four steps can be distinguished. The first step is the reversible binding of O2 to the Fe(II) center; this results in an absorbance signature with a maximum at 420 nm. This O2 complex decays with a rate constant that is 18-22 fold faster than the turnover number with either amino acid, setting a the lower limit for the rate constant for O2 activation. The rate constant for the third step agrees well with the pre-steady state of formation of 5-hydroxytryptophan or tyrosine from rapid-quench product analysis. The rate constant for the fourth step agrees well with the turnover number. Overall, these results show that O2 activation is fast and turnover with each amino acid is limited by hydroxylation and release of a product, with the former step being about 4-fold faster than the latter.

The field of "Oxygen Activation" has attracted considerable interest recently, not only because it presents challenges in those fields of basic research that aim to understand the fundamental aspects of chemical and biological reactions that involve dioxygen, but also because of its wide range of practical implications in such diverse fields as medicine, synthesis of pharmaceuticals and other organic compounds, materials science, and atmospheric science. This is the second of two volumes that focus on the subject of oxygen activation, the first slanted toward chemistry and the second toward biological chemistry. We planned these volumes to be more general than many monographs of this sort, not as detailed summaries of the authors' own research but rather as general overviews of the field. Our choice of topics was strongly influenced by our syllabus for a course entitled "Oxygen Chemistry," which two of us have twice taught jointly at UCLA. Definition of important issues, horizons, and future prospects was an important goal, and, although totally comprehensive coverage was not possible, we believe that we have chosen a representative selection of research topics current to the field. We have targeted this work to a diverse audience ranging from professionals in fields from physics to medicine to beginning graduate students who are interested in rapidly acquiring the basics of this field.