Normal vs Cancer Cell Metabolism and How PET Scans Work

 [This is my current understanding of the latest ideas on how cellular metabolism works with respect to cancer based on reading a few articles.]

Cells require ATP in order to survive, as well as fulfill whatever duties they have to the organism as a whole. ATP isn't just floating around for free in unlimited amounts for cells to take up and use, so each cell has to manufacture it's own supply. For people eating a normal diet, glucose is the primary raw material used by cells to manufacture ATP. However there are two different methods the cell can use to generate ATP using glucose.

1. Mitochondria: A single glucose molecule can be processed by mitochondria in the presence of oxygen to produce 32 molecules of ATP.
2. Cytosol: Cellular machinery exists in the cytosol which is capable of rapidly producing 2 molecules of ATP from a single molecule of glucose without requiring oxygen as part of the process.

These two processes correspond to the "aerobic" vs "anaerobic" pathways. Running glucose through the mitochondria takes extra time, but is massively more energy efficient than processing glucose directly in the cytosol (specifically, you get 16 times more energy from a given amount of glucose if you process it through the mitochondria). But you need oxygen to process glucose through mitochondria, so if the cell runs short of oxygen (ie. you are running the 400 yard dash) processes in the cytosol will kick in to assist in the production of ATP. However, as a side effect they will also put out lactate and hydrogen ions, which change the pH of the cell and lead ultimately to inability of the muscle cell to contract, the sensation muscle burn, and huffing and puffing.

[Processing glucose through mitochondria also produces byproducts such as reative oxygen species (ROS) but we're not worrying about that right now.]

Cancer cells, however, appear to have dysfunction mitochondria, so they are unable to generate ATP by running glucose through mitochondrial processes.

This puts the cancer cell in a difficult position. All cells need a certain amount of ATP just to survive. For the sake of argument, let's say these example cells need to be able to manufacture 96 molecules of ATP per minute or else they will die. To achieve that, the non-cancerous cell simply needs to transport three molecules of glucose from the extracellular fluid and use oxygen in the mitochondria to produce 96 molecules of ATP.

On the other hand, because its mitochondria doesn't work, a cancer cell has to transport 48 molecules of glucose across the cell membrane and process all of them in the cytosol to produce the same 96 molecules of ATP that only required 3 molecules of glucose for the normal cell. In the process, the cancer cell generates a lot of lactate and hydrogen ions, which alter the pH of the environment and according to some of the articles I've read may contribute to some of the pathological traits of tumors including encouraging them to metastasize.

So, compared to normal cells, cancer cells are like mutants which burn through enormous amounts of glucose. One of the early clues that cancer was related to glucose metabolism came from patients with uncontrolled type I diabetes (prior to insulin therapy I assume). Researchers could tell when these diabetic patients got cancer because the excess glucose normally spilling out in their urine would disappear because it was being devoured by their cancer cells.

[BTW that implies that cancer cells are able to transport the glucose across the cell membrane without the action of insulin, which I think I've heard is possible, but I'm not familiar with the details of how glucose transporters and insulin work.]

With this background you can see why tumors can be detected using radioactively labeled glucose. If you imagine that each glucose molecule comes with a radioactive tag (little red stars in the figures below), here is what the normal cell would look like after producing 96 molecules of ATP.

In contrast, here is the cancer cell after making 96 molecules of ATP.

So the important question is whether or not it is possible to fight cancer by limiting the availability of the large amounts of glucose it needs to survive.