Peter Attia· MD
The real surprise was when we got to the molecular mechanism. And that was that you had to have fructose and glucose because the actual carbon atoms that were being used to grow the tumor were were coming from the glucose and not from the fructose. And what the fructose was doing is when it went into the polyp, it was converted to fructose 1-phosphate by an enzyme called ketohexokinase, also called fructokinase. That enzyme's only found in three tissues in any significant concentration, the liver, the kidney, and the gut. And so these polyps, like the normal gut cells, have that enzyme. that has been something of a mystery of why that enzyme exists at that location. But in any event, it does. What happens is the fructose goes in, it gets phosphorylated by that enzyme, and it happens very rapidly. It's a very active enzyme. And that drops the ATP level in the cell because you're consuming ATP to phosphorylate that fructose that's coming in. Now, I mentioned earlier that the thing with the Warburg hypothesis is that In order to get glucose to flux at a high rate into a cell, you have to drop the ATP level. Well, this is a way to drop the ATP level. Instead of consuming it in some other way, you're consuming it by phosphorylating the fructose. There's an additional complication, or not complication, but intervention that is also important, which is once you start doing glycolysis at a higher rate, the process of doing glycolysis incorporates an inorganic phosphate to make a doubly phosphorylated and 1,6-bisphosphate. And so that additional consumption of inorganic phosphate drops a negative regulator of inosine deaminase, and that drops the ability to keep ATP synthesis going on in the cell. So the combination two drops the ATP level dramatically. And now the glucose that's coming in is flooding through glycolysis, but it's going into all these anabolic processes. It's being used to make lipids. We see all the label from glucose going into fatty acid synthesis and serine synthesis and nucleotide synthesis going up five or tenfold. It's really quite dramatic what happens. But if you leave the fructose out, even though the glucose gets in the cell, it can't go through glycolysis at a high rate, and so you don't get growth. You have to have both molecules. The carbon atoms are coming from the glucose. The fructose is basically driving the kinetics. Exactly.