Relation of Cell Growth to ATP

Hi Ashley, Thank you for your comment. I'm unsure if you meant this as a question, but if so, sure it's sharable. Gene and Richard

Chris, to elaborate further, as in our publication in 2009, the inhibition of pyruvate dehydrogenase by abundant acetyl CoA (derived from fatty acids or ketone bodies) and of phosphofructokinase by TCA cycle citrate is called the 'Randle cycle', from publications by Randle and coworkers in the 1960's and '70s. This inhibition generally doesn't occur in many free living people nowadays who eat their fat together with much carbohydrate (e.g. chocolate cake or buttered mashed potatoes) because the carbs stimulate insulin, thus driving excess glucose AND fatty acids into many cells with insulin sensitive GLUT4 transporters (e.g. adipose). The insulin also inhibits lipolysis and KB production. Randle et al, by comparison, performed their experiments under conditions of glucose and insulin clamping in ex vivo preparations. Under these conditions an increasing supply of fatty acids or KB's will in fact inhibit glycolysis. (A proper explanation of the Randle cycle was well clarified by Robert Wolfe and colleagues in the 1990's). Meanwhile the GLUT1 transporter on the membranes of many aggressive cancer cells is not insulin sensitive and has excellent (and constant, i.e. similar to clamped) transport kinetics of glucose. Under these conditions we postulated that added KB's would indeed inhibit glycolysis in cancer cells, similar to the conditions of Randle's clamped experiments.

yes, it makes sense!

Chris--Yes. The hypothesis is that overexpression of UCP2 in the cancers (& not in control fibroblasts) results in inefficient ATP production in the TCA cycle from added acetoacetate, and therefore reduced cell proliferation/growth, in the cancer lines only. (We haven't tried other percentages of AcAc, 'though that would be of interest).