Studies Of Caloric Restriction, Resveratrol And Sirt1 Demonstrate A ?Metabotype’ Continuum From Cellular Rejuvenation To Aging To Cancer
|
high rates, via some kind of chemiosmotic shuttle, for anabolic purposes, or in some combination, thereof, by some unknown mechanism(s). Thus, he began a literature search and, among other things, he ran into the Warburg debacle. But, being socially unsophisticated, he pressed on, and he pressed on because he found something very interesting, so interesting, in fact, that he virtually abandoned his wet lab (hands on) research for a mental form of research. In mental research, one reviews the work of other researchers in the hopes of ‘an unique synthesis of thought’, or, in other words an overlooked ‘big picture’, that, in this case, might also be suitable for a PhD dissertation. First, G. Bambeck found that there were a lot of cancer cell mitochondria vs. normal cell mitochondria papers out there, a number of them showing that Warburg’s respiratory defect was not there, in more than just a few cases. What he did find, in every cases where the data was taken, that net mitochondrial ATP production on a per mitochondrion and/or, more importantly, per cell basis, was significantly lowered compared to normal dividing cells. He further noted that mitochondrial net ATP synthesis shortfall could be due to low mitochondrial numbers per cell, inefficient electron transport, increased NAD/NADH shuttle export of reducing power, inefficient coupling of ATP formation to hydrogen chemiosmotic potential, a shift in the ATP synthetase to ATPase equilibrium dynamics or some fundamental metabolic Km shift in the chemical pathway linking glycolytic end products to the Krebs cycle. Anything that would block the connection between the NAD/NADH redox coupling to ATP formation, could tip the balance of carbon flow to anabolism. Most importantly, these mitochondrial shortfalls of ATP production could change the glycolytically produced to mitochondrially produced ATP production ratio by over 1000%. He proposed that this ratio differential forced fuel dependency upon glucose while simultaneously forcing other metabolites, reducing power and ATP energy flux toward anabolism. In the light of modern discoveries, to be discussed later, one could say that such a system pre-adapts the cell, metabolically, for a more uncontrolled growth format when not necessarily signaled by a growth factor: a precancerous state or hyperplasic non-dividing growth condition, as one might have it. If carcinogenesis is a multi-step process, why not have a metabolic process, or a progression toward a metabolic state that predicates the terminal process when suitable mutations and their associated stimuli arrive? G. Bambeck optimistically presented his conclusions to the scientific community with the expected dismissive results. Even though his dissertation was of a somewhat heretical nature, he received his PhD because the logic was essentially sound. But with nowhere to publish and nowhere to work on his findings, he evaporated from obscurity to nothingness in the annals of cancer research. Instead, he plied his trade in medical diagnostics and research tool technologies. The tools of 1975-1980 were not available to address a rationale for the collapse of mitochondrial efficiency in cells. For one, there seemed to be too many ways for it to happen. Gene switches and gene switching systems were just in their early days of initial elucidation. There were simply too many unknowns and alternatives. G. Bambeck took a stab at the problem, and notioned that reactive oxygen species (ROS), called free radicals at the time,
Related posts:
|
