Why Cancer Cells Waste So Much Energy (mit.edu) 31
MIT News: In the 1920s, German chemist Otto Warburg discovered that cancer cells don't metabolize sugar the same way that healthy cells usually do. Since then, scientists have tried to figure out why cancer cells use this alternative pathway, which is much less efficient. MIT biologists have now found a possible answer to this longstanding question. In a study appearing in Molecular Cell, they showed that this metabolic pathway, known as fermentation, helps cells to regenerate large quantities of a molecule called NAD+, which they need to synthesize DNA and other important molecules. Their findings also account for why other types of rapidly proliferating cells, such as immune cells, switch over to fermentation. "This has really been a hundred-year-old paradox that many people have tried to explain in different ways," says Matthew Vander Heiden, an associate professor of biology at MIT and associate director of MIT's Koch Institute for Integrative Cancer Research. "What we found is that under certain circumstances, cells need to do more of these electron transfer reactions, which require NAD+, in order to make molecules such as DNA." Vander Heiden is the senior author of the new study, and the lead authors are former MIT graduate student and postdoc Alba Luengo PhD '18 and graduate student Zhaoqi Li.
Fermentation is one way that cells can convert the energy found in sugar to ATP, a chemical that cells use to store energy for all of their needs. However, mammalian cells usually break down sugar using a process called aerobic respiration, which yields much more ATP. Cells typically switch over to fermentation only when they don't have enough oxygen available to perform aerobic respiration. Since Warburg's discovery, scientists have put forth many theories for why cancer cells switch to the inefficient fermentation pathway. Warburg originally proposed that cancer cells' mitochondria, where aerobic respiration occurs, might be damaged, but this turned out not to be the case. Other explanations have focused on the possible benefits of producing ATP in a different way, but none of these theories have gained widespread support. In this study, the MIT team decided to try to come up with a solution by asking what would happen if they suppressed cancer cells' ability to perform fermentation. To do that, they treated the cells with a drug that forces them to divert a molecule called pyruvate from the fermentation pathway into the aerobic respiration pathway.
Fermentation is one way that cells can convert the energy found in sugar to ATP, a chemical that cells use to store energy for all of their needs. However, mammalian cells usually break down sugar using a process called aerobic respiration, which yields much more ATP. Cells typically switch over to fermentation only when they don't have enough oxygen available to perform aerobic respiration. Since Warburg's discovery, scientists have put forth many theories for why cancer cells switch to the inefficient fermentation pathway. Warburg originally proposed that cancer cells' mitochondria, where aerobic respiration occurs, might be damaged, but this turned out not to be the case. Other explanations have focused on the possible benefits of producing ATP in a different way, but none of these theories have gained widespread support. In this study, the MIT team decided to try to come up with a solution by asking what would happen if they suppressed cancer cells' ability to perform fermentation. To do that, they treated the cells with a drug that forces them to divert a molecule called pyruvate from the fermentation pathway into the aerobic respiration pathway.
Removing the fermentation (Score:5, Informative)
I would really like to know if the cancer was unable to properly reproduce after removing pyruvate from the fermentation chain.
Anything that slows cancer is good in my book.
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The findings suggest that drugs that force cancer cells to switch back to aerobic respiration instead of fermentation could offer a possible way to treat tumors. Drugs that inhibit NAD+ production could also have a beneficial effect, the researchers say.
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So cancer is really a bunch of drunk cells (Score:3)
...out on a joy-ride.
Lactic Acid Cycle (Score:5, Informative)
For those who took biology in college.
Apparently it's also called "lactic acid fermentation".
It's the thing that causes muscle burn in intense exercise when your ATP stores have gone bust. (not cramps, that's potassium).
Re:Lactic Acid Cycle (Score:5, Funny)
> It's the thing that causes muscle burn in intense exercise
Slashdot users: I am unfamiliar with that which you speak of
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> It's the thing that causes muscle burn in intense exercise
Slashdot users: I am unfamiliar with that which you speak of
Exercise...
ex...er...cise
ex...ar...size
Eggs are sides
...for bacon...
BACON
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Doctor Who were way ahead of you.
https://m.youtube.com/watch?v=... [youtube.com]
Egg stir min:8 -> exterminate.
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Anybody keeping a sourdough starter or making natural pickles or pepper mash ferments also understands lactic acid fermentation, at least the basics of it.
Which makes me wonder if cancer tastes like pickles or sourdough. Damn my brain.
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Considering dogs often detect cancer by sniffing it out, it's probably closer to sourdough.
Dogs don't even have to be particularly trained to detect cancer - they often just show an intense interest in a particular spot on your body which leads to the doctor examining it and finding cancer. It's likely they're smelling the sour milk and they're interested, dogs being dogs.
But this probably works only on cancers that are close to
You don't get it! (Score:4, Funny)
Bits missing from summary (Score:5, Informative)
They saw, as others have previously shown, that blocking fermentation slows down cancer cellsâ(TM) growth. [..]
When the researchers treated the cells with a drug that stimulates NAD+ production, they found that the cells started rapidly proliferating again, even though they still couldnâ(TM)t perform fermentation. This led the researchers to theorize that when cells are growing rapidly, they need NAD+ more than they need ATP.[..]
The findings suggest that drugs that force cancer cells to switch back to aerobic respiration instead of fermentation could offer a possible way to treat tumors. Drugs that inhibit NAD+ production could also have a beneficial effect, the researchers say.
keto diet (Score:2)
Re:keto diet (Score:5, Informative)
>On a keto diet, there's less sugars available for fermentation.
On a 100% fat and protein diet (think pre-westernized African tribespeople), free of linoleic acid (a polyunsaturated, omega-6 fat), there is less sugar available for fermentation. Lean and very little cancer.
On a 90% carb diet, free of linoleic acid (think pre-westernized pacific islanders), there is less sugar available for fermentation too. Lean and very little cancer.
Your great grandparents ate carbs and were probably lean and they certainly had a lower risk of cancer that we do today - they had little linoleic acid in their diets.
Dietary sugar isn't good for sure, but people have stayed healthy with low blood sugar on high sugar diets.
I eat carnivore, but I'm avoiding linoleic acid first and sugar second.
Linoleic acid has a low F/N ratio (compared to saturated fats and so suppresses satiety signaling within the mitochondria by suppressing the voltage differential at the mitochondrial boundary. Also, being unsaturated, linoleic acid has a bend in it. The mitochondrial boundary (that keeps the ions apart like a battery's membrane) is made from saturated fats because they're straight and so line up an provide a consistent membrane. Linoleic acid, when in excess gets into the boundary and renders it porous, so the charge on either side of the boundary can just leak through an equalize. There goes your efficient ATP production and now you feel hungry despite eating a low cab diet.
Linoleic acid drives carb intolerance and suppresses satiety.
The ratio of Linoleic acid to saturated fats in the fat in our bodies has been going up for a long time, driven by changes in the fats we eat (feeding grain to cows, seed oils replacing lard and tallow, etc) in line with rates of obesity an cancer..
So - grass fed ruminant meat, eggs from happy chickens, the occasional fish, heavy cream from grass fed cows. It takes a few years to swap out all the bad fats in your cells, but it can be done. Mix in a bit of fasting to switch between anabolic and catabolic states so you're tearing down and rebuilding cells with the available, healthier fats.
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Some scientists seem to think that linoleic acid is the bees knees... who to trust?
https://www.hsph.harvard.edu/n... [harvard.edu]
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Some scientists seem to think that linoleic acid is the bees knees... who to trust?
https://www.hsph.harvard.edu/n... [harvard.edu]
Trust the ones with hypotheses that fit not just just the data they chose, but the historical and anthropological data too.
Harvard is probably the worst in terms of producing flawed nutrition science.
These people were first in line to promote low fat diets, hydrogenation, ideas that LDL is a cause of disease rather than a response to it and other known incorrect things.
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As a little thought experiment, consider how LA is good when populations have been getting fatter with increases in diabetes and cancer in line with the LA component of the diet over the last century. Wouldn't the reverse be the case if it was true that it was a health giving fat? Sugar consumption has gone the same way, but it doesn't line up as well.
At the cell level, we know how sugar acts roughly the same way as alcohol on the liver, leading to fat in the liver and the predictable consequences of that.
W
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Re:keto diet (Score:4, Informative)
Fat is catabolized to ketone bodies via Acetyl-CoA, which are metabolized directly. Glucose is not involved.
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Smell Cancer (Score:5, Interesting)
I've heard of dogs and even people that can smell certain cancers with surprising accuracy. I wonder if the smell is caused by this different form of ATP production?
Re: Smell Cancer (Score:2)
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Yes, but from exercise, this is in the muscles where it won't escape. If it's in the lungs, then you'll have a much better pathway for it to reach a dog's nose.
In any case, I hope they've studied the smells enough to determine which chemical is being released so that they understand the pathway.
Who knew (Score:2)
The solution to the obesity epidemic is cancer. Isn't nature beautiful?
Come again ? (Score:2)
"Since then, scientists have tried to figure out why cancer cells use this alternative pathway, which is much less efficient."
[...]
Since Warburg's discovery, scientists have put forth many theories for why cancer cells switch to the inefficient fermentation pathway."
Car analogy ... (Score:3)
But it like driving a Tesla in through the wind swept plains of Indiana, in winter, when out side temp is 2 deg F. Praying the battery will last till the Mishawaka supercharger. The gasoline car on the other hand generates so much waste heat (NAD+), it can be repurposed heat the cabin (synthesize DNA).
So, in short, cancer cells drive gasoline cars, Normal cells drive battery electric car. Agree, Rei?
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I know... I know... Attempted murder!
(Once you go over the top,... in for a penny... in for a pound)
Paradox?? (Score:2)
Cancer is just cells reverting to an older state in evolution.
Cells would naturally grow like that, but us more modern lifeforms have an inhibitor on top of that mechanism, to slow it down. Cancer is just when the inhibitor fails. So the older mechanism dominates again.
And it makes sense that then, older ways of using energy would come back with it too.
How's that been a "paradox" for anyone but he NIH crowd?