GAPDH: Biological Properties and Diversity (Advances in Experimental Medicine and Biology Book 985)

The book represents a comprehensive review and synthesis of the biomedical literature that spans over a half-century on a single protein called glyceraldehyde 3-phosphate dehydrogenase (or, GAPDH). Due to the protein’s involvement in a vast array of cellular activities, GAPDH is of interest to the cell biologist, immunologist, virologist, biochemist etc. The protein has a significant role in fertility, cancer and neurodegeneration, suggesting that this book can be a vital resource for drug development. GAPDH function may provide insight into anesthesia. Furthermore, GAPDH is highly conserved meaning that the protein found in microorganisms, such as pathogens, remained relatively unchanged in evolution. Pathogens use GAPDH as a virulence factor, offering a unique challenge in developing anti-microbial agents that target this protein. To the evolutionary biologist, a book on the multi-functionality of GAPDH provides a focal point for a cogent discussion on the very origin of life. GAPDH (glyceraldehyde 3-phosphate dehydrogenase) is more than just a glycolytic enzyme. An unprecedented amount of literature demonstrates that GAPDH has an astounding multiplicity of function. This diversity is not simply due to cell compartmentation (i.e. redistributing glycolytic energy to where it is needed), although this feature is undoubtedly important and discussed in the book. GAPDH integrates glycolysis with other cellular processes. This concept of integration cannot be understated. But, there is more. GAPDH actively participates in numerous non-glycolytic cellular events that fall into very broad categories including the cell infrastructure and the transmission of genetic information. Some of GAPDH's biological properties are completely non-intuitive given the current undergraduate textbook understanding of this glycolytic enzyme. For example, GAPDH binds to select phospholipids and catalyzes organelle biogenesis. It has fusogenic properties, enabling it to be actively involved in nuclear envelop reassembly, autophagy and membrane trafficking. Human macrophages exhibit surface-localized GAPDH with receptor function. As scientists, we are trained to consider GAPDH as a soluble cytosolic dehydrogenase enzyme. The literature observations - as described in this book - tell us something quite different. Besides oxidoreductase activity, GAPDH exhibits peroxidase, uracil DNA glycosylase, nitrosylase, mono-ADP-ribosylase, esterase and phosphotransferase activity. GAPDH binds membrane transport proteins, G-proteins, poly-nucleotides, adenines, specific lipids, select carbohydrates, cytoskeletal proteins, nuclear import and export proteins, diverse ATPases, molecular chaperones and other molecules Front Matter....Pages i-xiv Basic Biology of GAPDH....Pages 1-36 GAPDH and Intermediary Metabolism....Pages 37-59 Compartmentation of GAPDH....Pages 61-101 Functional Diversity....Pages 103-147 GAPDH, as a Virulence Factor....Pages 149-178 Target for Diverse Chemical Modifications....Pages 179-206 Dynamic Oligomeric Properties....Pages 207-247 Multiple Binding Partners....Pages 249-267 GAPDH in Anesthesia....Pages 269-291 Back Matter....Pages 293-295