Studies Of Caloric Restriction, Resveratrol And Sirt1 Demonstrate A ?Metabotype’ Continuum From Cellular Rejuvenation To Aging To Cancer
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Times Approximately 96% of a cell’s organic biomass consists of carbohydrates, fats, nucleotides and proteins. All four of these components can be either burned as fuel to power the cell, or as construction materials to replace defective parts in a quiescent cell or to build a new cell, as in the case of a dividing cell. In a normal, healthy quiescent cell, there is a balance between energy production and repair rates, so that the cell is said to be in homeostasis, or balance. In a normal, healthy dividing cell, growth factors set up a cascade of directives that order the cell to both increase its energy output and to import raw materials and build those raw materials into the components of a new cell. In short, nucleotides become RNA and DNA, amino acids become proteins, sugars become complex carbohydrates and fatty acids become lipids in a process called anabolism, while these same four starting materials can, alternatively, be burned as fuel to create energy, in a process called catabolism. The anabolic intermediate products can further assemble, by anabolism, into molecular assemblies, such as ribosomes, enzyme complexes etc., and, even further, into organelles such as mitochondria, lysosomes, a cell nucleus etc. Eventually, a whole new cell is formed. Cancer cells do this to, but as we shall see later, they don’t do it the same metabolic way as normally dividing cells. Instead, they do it more like in an extended metabolic version of aged cells. Although, what has been presented so far, is a gross oversimplification, suffice it to say, that by the middle of the twentieth century, a pretty sophisticated outline of many hundreds of the molecular trafficking pathways of the catabolic and anabolic interplay of organic molecular transitions, were mapped out. Wall posters in classrooms demonstrated these processes in a fashion analogous to watching automotive freeway traffic flow from an aerial view over a large city. Many discoveries have been made by observing disruptions in the flow, just as auto accidents cause clogs on off-ramps, on-ramps and thru-ways on the freeway system. Otto Warburg, in charge of a large research organization, and a highly respected molecular researcher of his day, being the early to mid twentieth century, thought he saw an intermediary metabolic perturbation both unique and specific to all cancer cells. More precisely, he hypothesized that this perturbation was critically confined to the catabolic, or fuel burning side of metabolism, but also set in motion an anabolic shift as a consequence. Even more specifically, he targeted the anomaly to the burning of a single fuel, glucose, to the relative exclusion of other fuels. Glucose is the primary, but, by no means, only fuel that is burned by cells of the body, and it is burned in two complex systems, called glycolysis and the Krebs cycle. Glycolysis obtains energy from glucose and other sugars by an anaerobic (non-oxygen utilizing) mechanism to produce ATP, an energy carrying molecule. The Krebs cycle, contained in an organelle called the mitochondrion, burns the glycolytic end product, pyruvate, utilizing an aerobic (oxygen consuming) mechanism to produce ATP. The burning with oxygen process sequentially strips hydrogens from the glycolytic end product, converting NAD to NADH2 and then couples the NAD hydrogens to oxygen to form water, while releasing the sugar carbons to form carbon dioxide. The formation of water is a stepwise process in which the energy of the hydrogens and their electrons are rejoined in
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