More on Metabolism

You are all probably aware of the important connection between cancer and metabolism. By the way, you might ask, "What is metabolism"? It means the sum total of all chemical reactions in your body. That's a pretty big topic! Interestingly, when I was a student, almost every laboratory had a large wall poster of 'metabolism' showing many of the classical biochemical pathways, some of which you might know, like the citric acid cycle. However, by the 80s basic biochemistry had become somewhat passe, as many considered we knew it all. Besides, molecular biology was just coming in to its own and as more and more papers on genomics and gene expression were published, fewer scientists were interested in studying biochemistry which had become very 'old school'.

But lets flash back even further to the 1920s when the study of biochemistry was in full swing as many of the aforementioned classical pathways were being worked out. An amazingly prescient scientist, Otto Warburg, made the observation that cancers had a unique biochemical signature he referred to as aerobic glycolysis. Glycolysis is the conversion of glucose to pyruvate which when there's enough oxygen around enters mitochondria where it can be further metabolized to stoke oxidative phosphorylation which makes our currency of energy (ATP).  In the absence of oxygen, pyruvate stalls outside mitochondria and is converted to lactate. Cancers, Dr. Warburg observed, have very accelerated glycolysis and convert most of the resulting pyruvate into lactate even in the presence of oxygen...hence, aerobic glycolysis (note this is a slight misnomer given that glucose - pyruvate covers glycolysis; maybe accelerated, aerobic, glycolytic lactate production would be more accurate...whew). Anyway, the amazing thing is that Otto was right!!! And as this signature has been confirmed again and again for a variety of cancers, more and more interest is accumulating in studying the biochemistry of cancer. That means, all those old-school wall posters of my youth are coming back to the laboratory! Now, we're looking at an intersection of biochemistry and molecular biology in many cancer-focused laboratories....and some of these are likely to have real importance for EHE. 

Interestingly, although it was assumed that transformation of cells to cancer causes the acceleration of glycolysis typical of cancers, it's recently been considered that the reverse is true, too: acceleration of glycolysis could promote cell proliferation typical of cancer. For example, it was recently shown that metabolic flux through one of the several enzymes required for normal glycolysis, phosphofructokinase (PFK), seems to turn on TAZ....the protein that is active in EHE. Although this effect is 'upstream' of TAZ, it's conceivable that dampening glycolysis could also slow down this signaling pathway and reduce one of the signals activating TAZ.....possibly even TAZ that is mutated by the disease-defining translocation of EHE. OK, that ice is somewhat thin, since upstream signals might be irrelevant to a mutation like the one in EHE, that constitutively (persistently) activates TAZ. However, let me go out even further onto the thin ice......some people, like Kris Karr believe in the benefits of a special diet. I don't hold with holistic medicine, but I wonder if there might something there. Is it possible that funneling tons of simple carbs down the glycolytic pathway causes PFK to turn on TAZ? Is it possible that the opposite is true: by eating well she's taming the effect of glycolysis on TAZ?