X-Message-Number: 27428 From: "Basie" <> Subject: evolutionarily conserved capacity Date: Tue, 13 Dec 2005 20:31:50 -0500 Nutrition & Metabolism 2005, 2:30 doi:10.1186/1743-7075-2-30 The electronic version of this article is the complete one and can be found online at: http://www.nutritionandmetabolism.com/content/2/1/30 Received 22 August 2005 Accepted 21 October 2005 Published 21 October 2005 2005 Seyfried and Mukherjee; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Keywords: glioma, vascularity, caloric restriction, ketone bodies, metabolic control analysis, angiogenesis, apoptosis, inflammation, Warburg Outline Abstract Abstract Introduction Metabolic Control Analysis Energy Metabolism in Normal Brain Cells Ketones and Free Radicals Energy Metabolism in Brain Tumors Dietary Energy and Brain Cancer Metabolic Control of Brain Cancer: An Evolutionary Perspective Abbreviations Acknowledgements References Malignant brain tumors are a significant health problem in children and adults and are often unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration, malignant brain cancer is potentially manageable through changes in metabolic environment. A radically different approach to brain cancer management is proposed that combines metabolic control analysis with the evolutionarily conserved capacity of normal cells to survive extreme shifts in physiological environment. In contrast to malignant brain tumors that are largely dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (?-hydroxybutyrate) for energy in vivo when glucose levels are reduced. The bioenergetic transition from glucose to ketone bodies metabolically targets brain tumors through integrated anti-inflammatory, anti-angiogenic, and pro-apoptotic mechanisms. The approach focuses more on the genomic flexibility of normal cells than on the genomic defects of tumor cells and is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with dietary energy restriction and the ketogenic diet. >Evolutionarily conserved capacity of normal cells to survive extreme shifts >in physiological environment. >Normal neurons and glia readily transition >to ketone bodies (?-hydroxybutyrate) for energy in vivo when >glucose >levels are reduced. The above quote is of importance to cryonics. Basie Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=27428