Book Reviews

Vitamin-Dependent Multienzyme Complexes of 2-Oxo Acid Dehydrogenases: Structure, Function, Regulation and Medical Implications

“Dr. Bunik has produced a comprehensive, detailed and authoritative account of the biochemistry, enzymology and regulation of this important family of multienzyme assemblies that control key steps in the major pathways of central metabolism. Their involvement in oxidative stress responses and disease states including cancer and neuropathological conditions linked to glutamate toxicity and acetylcholine synthesis is also discussed in detail. This book represents a distinctive and significant contribution to this important area of research, providing an ideal source of information for new or experienced researchers alike.” - John Gordon Lindsay, Ph.D., Professor of Medical Biochemistry (Honorary), University of Glasgow, Institute of Molecular, Cell and Systems Biology, Glasgow, Scotland, UK

"As a life-long enzyme enthusiast and scholar of thiamine and redox biology, I am captivated by the novel insights that Victoria Bunik has narrated in her monograph on vitamin-dependent multienzyme complexes. This work presents new dimensions in the actions of the age-old B-vitamin, thiamine, and delineates the interdependent actions of the various catalytic functions of the 2-oxo acid dehydrogenases, characterizing rate-determining conformational changes in the macromolecular structure and distinguishing key progressive reactions from side reactions. Difficult mechanistic details of catalysis such as the role of thiyl radical intermediates are portrayed with skill. Besides regulation of gene expression, an in-depth consideration of various mechanisms of post-translational regulation of the enzyme complex provides a valuable resource for investigators entering this field of study. Finally, the functional importance of these enzyme complexes in health and disease is brought to the fore. This monograph by Bunik is a scholarly tour de force which will capture the interest and satisfy the creative imagination of investigators and students over a broad range of the biomedical sciences." - John J. Mieyal, Ph.D., Professor and Vice-Chairman of Pharmacology, Case Western Reserve University, Cleveland, Ohio USA

"Victoria Bunik, who worked successfully also here in Tuebingen, wrote this excellent book, comprehensive and always up to date in any respect. Never I read a better book in this important field. It is absolute worthwhile to read it!" - Peter Bohley, Professor of Biochemistry, Emeritus, Interfakultaeres Institut fuer Biochemie, Tuebingen, Germany

"This book is an important contribution by the world leader in this area. Interest in the 2-oxo acid dehydrogenases has exploded. New and powerful tools for studying their structure and function have stimulated new understanding. Roles for these enzymes beyond energy metabolism and ROS production including regulation of protein cross talk and transcription are now apparent. In addition, we now know these enzymes have a surprisingly key role in cancer, stem cell biology, neurodegeneration and many other areas. In combination, these new ideas have created a large literature that requires the kinds of syntheses that has been accomplished in this outstanding book." - Gary E. Gibson, Ph.D., Professor, Brain and Mind Research Institute Weill Cornell Medicine, Burke Medical Research Institute, NY, USA

"In her concise book prof. Victoria Bunik summarizes comprehensive information on multienzyme complexes of the dehydrogenases of pyruvate, 2-oxoglutarate and branched-chain 2-oxo acids. Unique nature of the molecular conveyers, with their usage of multiple vitamin derivatives and precise regulation, is shown to be appropriate for metabolic checkpoints which the complexes occupy." - Slawomir Strumilo, PhD, Dr.Sci., Professor of Biochemistry, University of Bialystok, Poland

“This book gives an excellent overview of a multitude of aspects of 2-oxoacid dehydrogenase multienzyme complexes. Originally, the attention was mainly directed to the structure, function and regulation of the bacterial complexes. The introduction of genetic methods resulted in expression of separate components, crystallization and NMR. A wealth of detailed insights how rigidity and mobility are combined in these large multienzyme complexes was revealed. This is well described in Chapter 2, 3 and 4.

Presently this knowledge is being used to understand their function in mammalian systems. These complexes play a central role in energy metabolism of carbohydrates, fatty acids and amino acids. Because of this central function there is a strict regulation on a genetic level, by metabolites and by hormones. This is extensively discussed in Chapter 6. In Chapter 7 the role of these complexes is described with respect to homeostasis in normal physiology and under pathological conditions, e.g. cancer. Special attention is given to the role of these complexes in the metabolism of neurotransmitters in brain. For all of those who want to know about the present state of art of these intriguing multienzyme systems I can greatly recommend reading this review.” - Aart de Kok, PhD, former leader of the research on 2-oxo acid dehydrogenase complexes at the University of Wageningen, The Netherlands

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