This volume is concerned with the enzymes of the nervous system. Cerebral enzymes form the basis of the functional brain. They are needed for the control of the energetics of the nervous system, whether it be their release or their direction; for the elaboration of transmitters and for their destruction; for the synthesis, transport, and breakdown of all metabolites of the nervous system. They are indispensable for the control of the multitude of factors that govern our thinking and our behavior. They make it possible for us to comprehend what is taking place around us and perhaps to understand what may be in store for us. Enzymes are the stuff of life, and no living cell can be without them. They are the results of many millions of years of evolution, from the time when biological membranes first came into being and were folded to produce the first cells within which the earliest enzymes were wrought. Countless changes have taken place within them, so that, now, only those enzymes exist that play specific roles in the functions of the living cells of today. Those in the nervous system possess a mUltiple role: in the creation, maintenance, and ultimate breakdown of the component cells and in enabling consciousness, perception, memory, and thought to become possible. But though life may go on forever, the enzymes that make life possible will undergo the many changes involved in the evolutionary process.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases - and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume I untangles the web of these enzymes and their products, and relates them to function in health and disease. Phosphoinositide 3-kinases and 3-phosphatases have received a special focus in volume I, and recent therapeutic developments in human disease are presented along with a historical perspective illustrating the impressive progress in the field.

Major advances have been made in recent years in clarifying the molecular properties of the cytochrome P-450 system. These advances stem, in practical terms, from the generally recognized importance of cytochrome P-450 in the metabolism of drugs and in the bioactivation of xenobiotics to toxic products. The fascinating multiplicity and differential regulation of cytochrome P-450 isozymes, and their ability to catalyze extraordinarily difficult chemical transformations, have independently drawn many chemists and biochemists into the P-450 circle. Progress in the field, from a technical point of view, has been propelled by the de velopment of reliable procedures for the purification of membrane-bound enzymes, by the growing repertoire of molecular biological techniques, and by the development of chemical models that mimic the catalytic action of P-450. As a result, our understanding of the P-450 system is moving from the descriptive, pharmacological level into the tangible realm of atomic detail. The rapid progress and multidisciplinary character of the cytochrome P-450 field, which cuts across the lines that traditionally divide disciplines as diverse as inorganic chemistry and genetics, have created a need for an up-to-date evaluation of the advances that have been made. It is hoped that this book, with its molecular focus on the cytochrome P-450 system, will alleviate this need. The authors of the individual chapters have strived to emphasize recent results without sacrificing the background required to make their chapters comprehensible to informed nonspecialists.

Ribonucleases are a ubiquitous and functionally diverse group of enzymes that have a common ability to cleave RNA. Either through scission of internal phosphodiesters, or removal of nucleotides from RNA 5' or 3' ends, ribonucleases perform essential roles in gene expression and regulation, genome replication and maintenance, host defense, stress response, and viral strategies of infection. Ribonucleases have also served as highly informative models to understand virtually every aspect of biomolecular structure and function. The fifteen chapters in this volume are written by recognized researchers in the field, and provide in-depth analyses of the major ribonuclease families. Particular focus is given to the relation of ribonuclease structure and mechanism to biological function, as well as ribonuclease dysfunction in certain disease states. Other topics include the evolutionary genetics and functional diversification of ribonucleases, engineered ribonucleases as anti-cancer agents, the mechanisms of action of artificial ribonucleases, and ribonucleases as models to understand protein folding and stability. This volume should serve as an essential reference for a broad range of researchers and educators with interests in RNA metabolism, enzymology, and gene regulation.

The study of a single well-chosen substance, here aspartate transcarb amylase, can provide an excellent basis for a laboratory course. The student is introduced to a variety of scientific ideas and to many experi mental and interpretive techniques. This enzyme is readily available, is relatively stable, has an extensive literature, and its behavior has many facets: substrate inhibition, a large change in structure upon homo tropic activation by substrates, allosteric stimulation by ATP, allosteric inhibition by CTP synergistic with VTP, positive cooperativity for sub strates, negative cooperativity for CTP binding, and dissociation and reassembly of subunits Cand R2 from the holoenzyme CI\5. In addition 3 6 to the known biochemical aspects of these properties, the results ob tained here can be interpreted in the light of the high-resolution X-ray diffraction structures of the T and R forms, the low-angle X-ray scattering results, and the large number of mutants now available by recombinant DNA methods. Future development of this course could also involve part of these methods, as well as the carefully chosen experiments described here. This approach resembles research more than the approaches one usually finds in biochemical laboratory courses. A consistent develop ment of ideas about a single enzyme, which shows so many facets in its behavior, is sure to hold the interest of the student. Moreover, one explores a depth, and reasons to move forward, that are an essential part of research."

In September 1998 experts from 19 countries came together for an interdisciplinary discussion of the function of animal peroxidases, a family of enzymes embracing myeloperoxidase, eosinophil peroxidase, thyroid peroxidase and lactoperoxidase. Their papers have been updated for publication, yielding a wide-ranging overview of the state of the art. The chapters cover a wide range of topics, including three-dimensional structure of representative family members, their biosynthesis and intracellular transport, mechanism of action as well as applications to clinical medicine. They are of clinical relevance in, for example, arteriosclerosis, multiple sclerosis, infections, tumorigenesis, rheumatic diseases and hypothyroidism. This book forms an excellent introduction for anyone interested in the peroxidase family of enzymes.

Key Building Blocks via Enzyme-Mediated Synthesis, by Thomas Fischer and Jorg Pietruszka
*
Engineered Biosynthesis of Plant Polyketides: Structure-Based and Precursor-Directed Approach, by Ikuro Abe
*
Enzymatic and Chemo-Enzymatic Approaches Towards Natural and Non-Natural Alkaloids: Indoles, Isoquinolines, and Others, by Joachim Stockigt, Zhong Chen, and Martin Ruppert
*
Chemoenzymatic and Bioenzymatic Synthesis of Carbohydrate Containing Natural Products, by Bohdan Ostash, Xiaohui Yan, Victor Fedorenko, and Andreas Bechthold
*
Total (Bio)Synthesis: Strategies of Nature and of Chemists, by Alexandra A. Roberts, Katherine S. Ryan, Bradley S. Moore, and Tobias A.M. Gulder"

The development of agents capable of cleaving RNA and DNA has attracted considerable attention from researchers in the last few years, because of the immediate and very important applications they can find in the emerging fields of biotechnology and pharmacology. There are essentially two classes of these agents - nucleases that occur naturally inside cells and synthetically produced artificial nucleases. The first class includes protein enzyme nucle ases and catalytic RNA structured ribozymes that perform cleavage of the phosphodiester bonds in nucleic acids according to a hydrolytic pathway in the course of different biochemical processes in the cell. A different pathway is used by some antibiotics which cleave DNA via redox-based mechanisms resulting in oxidative damage of nucleotide units and breakage of the DNA backbone. The above molecules are indispensable tools for manipulating nucleic acids and processing RNA; DNA-cleaving antibiotics and cytotoxic ribonucleases have demonstrated utility as chemotherapeutic agents. The second class, artificial nucleases, are rationally designed to imitate the active centers of natural enzymes by simple structures possessing minimal sets of the most important characteristics that are essential for catalysis. A dif ferent approach, in vitro selection, was also used to create artificial RNA and DNA enzymes capable of cleaving RNA. Being less efficient and specific as compared to the natural enzymes, the primitive mimics are smaller and robust and can function in a broad range of conditions."

Prior to the start of the eighth meeting, I had the good sense to ask Professor Rosa Angela Canuto of Turin, Italy if she would help me organize the ninth meeting. She quickly suggested that both she and Dr. Guiliana Muzio, also of Turin, help plan the meet ing. Each of our previous eight meetings was a unique experience for the participants. The science was always outstanding and the presentations and discussions were excellent. By moving each meeting to a different part of the world we were able to experience exciting foods and cultural aspects of the world in addition to the science. The ninth meeting was no exception. We met from June 18 to 22 in the small mountain city of Varallo, Italy, the birth place of Dr. Canuto. Holding the scientific sessions in a several-hundred-year-old converted mansion and having an afternoon trip to either Lago Maggiore or Monte Rosa made some aspects of this meeting extremely memorable. An additional unique aspect of the social portion of the meeting was our ability to invite the townspeople to share with us a concert performed in an old church. Though the social and cultural aspects of the meeting were outstanding, the pur pose of the meeting was to exchange scientific information about the status of the three enzyme systems.

Gamma-Glutamyl Transpeptidases ( -GTs) are members of the N-terminal nucleophile hydrolase superfamily, enzymes that cleave the -glutamyl amide bond of glutathione to liberate cysteinylglycine. The released -glutamyl group can be transferred to water (hydrolysis) or to amino acids or short peptides (transpeptidation). -GT plays a key role in the gamma glutamyl cycle by regulating the cellular levels of the antioxidant glutathione, hence it is a critical enzyme in maintaining cellular redox homeostasis. -GT is upregulated during inflammation and in several human tumors, and it is involved in many physiological disorders related to oxidative stress, such as Parkinson's disease and diabetes. Furthermore, this enzyme is used as a marker of liver disease and cancer. This book covers current knowledge about the structure-function relationship of -GTs and gives information about applications of -GTs in different fields ranging from clinical biochemistry to biotechnology and biomedicine.

This volume represents a collection of lectures delivered by outstanding specialists in the fields of biophysics and of related scientific disciplines th during the 7 International Summer School on Biophysics held in Rovinj, Croatia from 14 to 25 September 2000 under the title "Super molecular Structure and Function ." This scientific-educational event was organized by the Ruder Boskovic Institute ofZagreb, Croatia with substantial material and intellectual support of a number of national and international institutions including the Croatian Biophysical Society (CBS), the International Union of Pure and Applied Biophysics (IUPAB), the International Centre for Genetic Engineering and Biotechnology (ICGEB) and the UNESCO Venice Office - Regional Office for Science and Technology for Europe (UVO-ROSTE). The seventh edition of the series of International Summer Schools on Biophysics, which was started in 198I, attracted more than 120 young researchers and post-graduate students coming from 27 countries of Europe, Asia, Africa and Latin America. Twenty-five outstanding experts in pure and applied biophysics presented the most advanced knowledge ofthis very interdisciplinary area of science during their lectures and round tables. It was commonly acknowledge that the Summer School achieved great success and fully reached its objectives. The success of the Rovinj Summer School was also due to the constantly growing attention being paid by scientific communities to younger generations of scientists, thanks also to the major outcomes of the World Conference on Science "Science for the Twenty-first Century: A New Commitment" held by UNESCO and ICSU in Budapest, Hungary in June 1999.

Presently, intensive and global attention is being devoted to "biotechnology"--the technology utilizing marvelous capacities of living things for human welfare. Each country is strongly promo ting its development. In particular, enzyme engineering, whose pur pose is to utilize efficiently enzymes, microorganisms, and cultured plant as well as animal cells as organic catalysts, is one of the main themes in the field of biotechnology. Under these circumstances, the Sixth Enzyme Engineering Confe rence was held at Kashikojima, Mie Prefecture, Japan from September 20 to 25, 1981, under the joint auspices of the Engineering Foun dation of New York and the Japanese Society of Enzyme Engineering. This series of international conferences has been held biannually since 1971. The first three and the fifth conferences were held in the United States and the fourth one was in the Federal Republic of Germany. This sixth conference was the first to be held in Asia; and it was significant that a number of participantGBP could visit Japany, which has produced successful achievements in the field of biotechnology.

Soil enzymes are one of the vital key mediators involved in nutrient recycling and the decomposition of organic matter and thereby in maintaining soil quality and fertility. This Soil Biology volume covers the various facets of soil enzymes, such as their functions, biochemical and microbiological properties and the factors affecting their activities. Enzymes in the rhizosphere, in forest soils, and in volcanic ash-derived soils are described. Soil enzymes covered include phosphohydrolases, lignocellulose-degrading enzymes, phenol oxidases, fungal oxidoreductases, keratinases, pectinases, xylanases, lipases and pectinases. Several chapters treat the soil enzymatic activities in the bioremediation of soils contaminated with pesticides and pollutants such as oil, chlorinated compounds, synthetic dyes and aromatic hydrocarbons. The role of soil enzymes as bioindicators is a further important topic addressed.

Enzyme kinetics has undergone very rapid growth and development during the past fifteen years and has been well received by the biochemical community. A cursory glance at the current biochem ical literature reveals the increasing popularity of enzyme ki netics1 yet, there are very few books available to guide the enzymologist who wishes to conduct kinetic experiments. This monograph was undertaken to provide the fledgling kineticist with an outline of contemporary initial rate enzyme kinetics. A large portion of the material contained in this book is presented in a second-year, graduate-level course in biochemistry at Iowa State University. I have found that the presentation in this course has enabled students without a strong background in math ematics to undertake initial rate studies at the research bench. The monograph obviously is more comprehensive than any course could be, and should permit similar accomplishment. As the title implies, the major emphasis of this monograph is on initial rate enzyme kinetics. I considered at length the advis ability of including chapters on integrated rate equations and on the theory and application of rapid reaction kinetics, such as rapid-mixing stopped-flow, and temperature-jump kinetics. These, however, are topics that would require a good deal of space to develop if they were to be helpful to the beginner."

Being small, shapeless and inert a gas molecule does not seem to be an enzyme's dream of a substrate. Nevertheless evolution has provided a host of enzymes which can interact specifically with gas molecules such as oxygen, carbon dioxide, nitrogen, hydrogen etc. Many of these enzymes play dominant roles on the world scene in biogeochemical cycles. On the cellular level they tend to be closely connected to the energy conserving apparatus. We define Gas Enzymology as the study of these enzymes. Historically, Gas Enzymology is a subspecialty of bioenergetics. Its foundations, technical as well as conceptual were laid by Warburg in his studies of the cellular combustion of nutrients. The Warburg apparatus supported the first thirty years of research in the field. It was succeeded by the Clark electrode which had its heyday during the period when the modern concepts of bioenergetics took shape. The Clark electrode, itself approaching thirty years of age, is now being sup plemented and in some cases replaced by the vastly more powerful membrane inlet mass spectrometer which measures with equal ease all dis solved gases of interest in biochemistry. It is our belief that future development of Gas Enzymology will be linked to the widespread exploit ation of this technique."

The second international symposium on Pectins and Pectinases was organized by Wageningen University and Research Centre and held in Rotterdam, May 6-10, 2001. This successful meeting was attended by around 130 participants from more than 20 countries representing almost all of the groups and industries working woridwide on pectins and pectinases. Following the first meeting on this subject held in December 1995, the symposium defInitely forms a platform for researchers and industries working in the fIeld, all within their own discipline and expertise. The symposium demanded a written account and this book is the resuit of that. It contains aIl keynote lectures and other oral presentations and provides an update about the current research. SignifIcant progress has been made in the last 5 years. This book provides an up-to-date insight into the research on pectin and pectic enzymes involved in their biosynthesis, degradation, modifIcation or utilization. The progress in the elucidation of the chemical structure of pectin and mode of action and 3-D structure of the pectin degrading enzymes allows us to identify and influence the functionality of pectins and pectic enzymes, both in vitra after isolation as weIl in the plants themselves (in planta). Other contributions deal with new applications of both pectin and pectin-degrading enzymes, while more and more attention is paid to health and nutritional aspects ofpectins. The book provides a 'state of the art' account for both beginners and experienced researchers of almost all disciplines of pectin research.

Post-translational protein modifications by members of the ubiquitin family are widely recognized as important regulatory control systems for a variety of biological pathways. Their influence on eukaryotic cellular metabolism is comparable to that of other modifi- tions such as phosphorylation, acetylation and methylation. The small ubiquitin-related modifier SUMO uses a conjugation and de-conjugation system closely related to that of ubiquitin itself; yet, the functions of the SUMO system are highly diverse and largely independent of the ubiquitin system. SUMO modification controls the activity of tr- scription factors and can influence protein stability, but it also contributes to nucleo-cy- plasmic transport, chromosome segregation and DNA damage repair. As a consequence, the SUMO system pervades virtually all areas of basic molecular and cell biology, and scientists from different backgrounds, including medical researchers, are likely to enco- ter SUMO in the course of their studies. This volume, SUMO Protocols, therefore aims at presenting a collection of methods relevant to SUMO research in order to make these tools available to biochemists, molecular and cell biologists as well as research-oriented clinicians not yet familiar with the system. In contrast to the ubiquitin system, which has been the subject of several reviews and methods collections, no practical compendium entirely devoted to SUMO has been p- lished.

This volume provides a unique collection of detailed chapters from some of the leading research groups in the world, many of which have made key discoveries in the field. This allows for particularly insightful discussion of the current understanding of Rho function.

Work on signal transduction pathways involving Rho family GTPases started some ten years ago. There is now a realization that these highly conserved molecular switches not only serve to coordinate cytoskeletal organization but also impact on diverse aspects of cell biology such as membrane trafficking, transcriptional regulation and mitotic progression.

Humans contain more than 20 Rho type GTPases. This volume not only presents a detailed phylogenetic analysis of Rho proteins, but also discusses the possible origins of the human members. Such an analysis of human Rho GTPases has not previously been attempted.

The book includes an overview of how Rho GTPases become activated which is complemented by an extensive Chapter by Darerca Owen and Helen Mott who unravel the beautiful molecular details given to us by the many structural studies of Rho GTPases.

The key areas currently being investigated in relation to these ubiquitous proteins are described for both in vitro and in vivo systems. These are presented in a format that ensures the reader can approach the topic with minimal background knowledge, while ultimately bringing the subject to the level of an expert. Timely and highly authoritative, this volume illuminates newer findings, particularly as they relate to Rho proteins in vertebrate biology.

This book covers the most recent developments in the analysis of allosteric enzymes and provides a logical introduction to the limits for enzyme function as dictated by the factors that are limits for life. The book presents a complete description of all the mechanisms used for changing enzyme activity. It is extensively illustrated to clarify kinetic and regulatory properties. Eight enzymes are used as model systems after extensive study of their mechanisms. Wherever possible, the human form of the enzyme is used to illustrate the regulatory features.

The recognition of oxidative stress as a major factor in health, aging, and disease has led to a surge in research aimed at uncovering effective countermeasures in the form of antioxidants. Unique in its two-fold protective function, alpha-lipoic acid has drawn unprecedented interest as a coenzyme in mitochondrial energy metabolism and as an antioxidant and cell redox modulator. Mounting data regarding its potential health benefits demands an authoritative, single-source reference to codify current knowledge and guide future research. A state-of-the-science compilation, Lipoic Acid follows the history of this potent coenzyme and the latest discoveries regarding the chemistry, biological action, and significance in energy production, antioxidant activity, and health. The book is divided into three sections: * Section I: Discovery and Molecular Structure reviews the early studies leading to the discovery of alpha-lipoic acid and explains the molecular structure, biosynthesis, and the characterization of lipoic acid and its chemical derivatives. * Section II: Metabolic Aspects describes in detail the human pharmacokinetics of alpha-lipoic acid including the lipoic acid-derived dehydrogenase complexes and their roles in energy metabolism. It also explains antioxidant activity and redox modulation and how lipoic acid induces Phase II detoxification enzymes through activation of Nrf2-dependent gene expression. * Section III Clinical Aspects discusses enzyme deficiency disorders and the effects of lipoic acid on insulin. It defines lipoic acid influence on signaling pathways and AMP-activated kinase, and considers the therapeutic implications for treatment of metabolic syndromes and the improvement of mitochondrial function by lipoic acid supplementation. Contributions from leading in

The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes."

Plant protease inhibitors are diverse in number and in specificity towards various proteolytic enzymes. This book focuses on the isolation, structure, characterization, physiochemical and physiological properties, synthesis, functions and mechanisms of action of plant protease inhibitors. It deals with their inhibitory effects on insects and pathogens and with their induction and introduction into plants by genetic engineering for plant protection. The induced resistance of insects to the inhibitors and the hazards to friendly insects are also discussed. Further, findings are presented on the cancer chemopreventive properties of the inhibitors at the cellular, tissue and organ levels and in the organism.

A quantitative description of the action of enzymes and other biological systems is both a challenge and a fundamental requirement for further progress in our und- standing of biochemical processes. This can help in practical design of new drugs and in the development of artificial enzymes as well as in fundamental understanding of the factors that control the activity of biological systems. Structural and biochemical st- ies have yielded major insights about the action of biological molecules and the mechanism of enzymatic reactions. However it is not entirely clear how to use this - portant information in a consistent and quantitative analysis of the factors that are - sponsible for rate acceleration in enzyme active sites. The problem is associated with the fact that reaction rates are determined by energetics (i. e. activation energies) and the available experimental methods by themselves cannot provide a correlation - tween structure and energy. Even mutations of specific active site residues, which are extremely useful, cannot tell us about the totality of the interaction between the active site and the substrate. In fact, short of inventing experiments that allow one to measure the forces in enzyme active sites it is hard to see how can one use a direct experimental approach to unambiguously correlate the structure and function of enzymes. In fact, in view of the complexity of biological systems it seems that only computers can handle the task of providing a quantitative structure-function correlation.

Enzymes in Action is a timely survey of a modern development in organic chemistry. It is clear that bioreagents demand that organic chemists think in a different way. If they do so, they will open up new avenues of exciting, new chemistry that will permit problems to be solved in an elegant way. The first section covers the concepts necessary to understand enzymes in molecular operations. The second section covers heteroatom enzyme chemistry, with considerable attention being given to the use of enzymes in the detoxification of chemical warfare agents and their application in environmental problems. The final section highlights the strategic use of enzymes in organic chemistry. It is clear that the term green chemistry' is appropriate, since enzyme mediated processes occur under mild, environmentally benign conditions, and enzymes enable chemists to perform new chemical operations that would otherwise be difficult to achieve at all.

This book is a fascinating overview of one of the first pharmacogenetic traits to be identified as responsible for genetic variation in response to drugs - the understanding of the arylamine N-acetyltransferases (NATs) is linked to many important therapeutic areas, particularly tuberculosis and also cancer. NATs have been important in the metabolism of established anti-tubercular drugs and also in carcinogenesis and susceptibility to bladder cancer. The reach of these enzymes spans pharmacology and therapeutics as well as toxicology and pharmacogenetics. The NAT genes are encoded in a highly polymorphic region of the human genome which has been explored for fine mapping in molecular anthropological studies.The book takes a wide ranging approach covering all aspects of the arylamine N-acetyltransferases from genetics to the chemistry and structural biology of the enzymes in the organisms in which they are found, from humans to bacteria and fungi where they appear to have distinct roles. The coverage is by experts in the field from across the globe.