I preface this post with saying: read it slowly and carefully. Look at the diagrams. It’s interesting as long as you can keep track of the key players. This is like what my husband said before we watched “The Departed.”
“You have to pay attention or it’s not going to make ANY sense.”
Enjoy!
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People need money to live. They use it to buy clothes, a home, food, cars, and anything in between. The money that cells use is called ATP. It’s a small molecule that holds lots of energy in its bonds that the cell needs to make proteins, replicate DNA, pass through the cell cycle checkpoints, etc.
People work to bring money home so how do cells make money?
They break down glucose! Glucose is specific kind of sugar that when broken down properly can give the cell a lot of ATP.
Figure 21.1 is showing you, in very brief and simple details, how a cell breaks down glucose to make ATP. It consists of three steps.
The first step is called Glycolysis (literally meaning the breaking of glucose). The final product of glycolysis is a molecule called pyruvate.
Pyruvate is then turned into citric acid.
Citric acid is then converted into several molecules before being turned back into citric acid again. This is called The Citric Acid Cycle (TCA).
These first two steps generate two other molecules: ATP and NADH (from NAD+).
The third and final step is called the Electron Transport Chain (ETC), which essentially turns NADH back into NAD+ and creates ATP. This final step generates many more ATPs than glycolysis or the TCA alone. This step also requires oxygen.
Figure 21.2 shows the same steps again with the important molecules highlighted in red.
Healthy cells take in glucose and turn it into ATP all day long as long as oxygen is plentiful (we are breathing). Think of this system as a nice 9 to 5 working man who consistently brings home money and can provide well for his family.
Cancer cells, on the other hand, are greedy. They want more money. They want as much as they can possibly get. Think of these cells as thieves, charlatans or con artists. Cancer cells grow rapidly and to do so they need a tremendous amount of ATP. The straight forward glycolysis to TCA /ETC just isn’t cutting it for them to grow the way they want to. So… they change.
Cancer cells accelerate the rate of glycolysis, which increases the amount of pyruvate and NADH around. This phenomenon is named “The Warburg Effect.” Increasing the rate of glycolysis ensures that more ATP is around in the cell (Figure 21.3).
However, the cancer cells have a problem. There is only a finite amount of NAD+ in the cell and if glycolysis is moving faster, then NAD+ is being depleted very rapidly. To continue its high rate of glycolysis, the cancer cell needs more NAD+. How does it get it?
It can wait for the TCA/ETC to catch up, but many times oxygen isn’t plentiful in tumors. Maybe there isn’t a blood vessel there yet to carry oxygen to it. Regardless, waiting isn’t for cancer cells. They want a more immediate solution.
The cancer cells choose an alternate path: they turn NADH back into NAD+ by turning pyruvate into lactate*. The details aren’t important, but what is interesting is that instead of pyruvate entering the TCA, it becomes lactate and isn’t useful to the cell for energy anymore.
This means that glycolysis is running at top speed and pyruvate is being used up as quickly as it’s made.
I said cancer cells are greedy. They want as much ATP as possible. Pyruvate isn’t available from glycolysis to run the TCA/ETC. If they could just get some more pyruvate from somewhere, then they could get the whole slew of ATPs from the TCA/ETC as well.
Where can the cell get more pyruvate? Where??
By breaking down glutamine, an amino acid used to build proteins. Cancer cells break down glutamine, turn it into pyruvate, and can now run the TCA/ETC again. This leads people to say that cancer cells are “glutamine addicted.” The need the glutamine to keep turning into pyruvate so the TCA/ETC can still run and pump out lots of ATP in addition to the lots of ATP made by glycolysis (Figure 21.4). The metabolism of cancer cells is quite ridiculous!
* - Turning pyruvate into lactate is what happens in our muscle cells during exertion. For example, if you are running and you start to feel as if you can’t go anymore, your muscles hurt or you just want to stop, this is because there isn’t enough oxygen around to allow pyruvate to turn to citric acid and run the TCA/ETC. The cell changes its metabolism so it can still generate some ATP and keep you running, but it isn’t enough as if the TCA/ETC was running. Eventually we tire and have to stop.
Glucose: a sugar molecule broken down by cells to make ATP
ATP: adenosine triphosphate, a molecule commonly referred to as the “energy currency of the cell.”
Glycolysis: the process by which glucose is turned into pyruvate.
The Citric Acid Cycle: aka TCA, part of metabolism that breaks down and recreates citric acid over and over again. It also generates some ATP and NADH from ADP and NAD+.
The Electron Transport Chain: aka ETC, part of metabolism that makes a lot of ATP from NADH and recreates NAD+ for glycolysis and the TCA.
REFERENCES
Alberts et al. “Molecular Biology of the Cell, 4th Edition.” Garland Science, New York, New York. (2002).
Warburg O (1956). "On the origin of cancer cells". Science 123 (3191): 309–14.
Kim JW, Dang CV (2006). "Cancer's molecular sweet tooth and the Warburg effect". Cancer Res. 66 (18): 8927–30
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