Fructose series part 1: fructose depletes ATP?

Fructose is the most evil monosaccharide there is according to most nutritionists out there.

One of the main reasons why is because it’s thought to deplete ATP. Glucose is thought to enter a cell on an insulin-dependent mechanism (GLUT4), whereas fructose doesn’t require insulin to enter a cell (GLUT2 and GLUT5).

Here’s what you’ll hear them say: “Fructose doesn’t require insulin to enter a cell, so it streams in, overwhelms the cell, and depletes ATP. Glucose requires insulin so its uptake is limited to insulin.”

My reply to that is: “Glucose can also enter a cell without insulin through other glucose transporters, such as GLUT1. In fact, research shows that the rate of glucose uptake is dependent on the amount of glucose in the blood. In the face of hyperglycemia, tissue glucose uptake is usually increased above normal even when insulin deficiency is severe.”

To which they respond:

Furthermore, it’s impossible for fructose to deplete ATP, even if you consume a very large amount of it, and here’s why… Let’s look at glycolysis (on the left) and fructolysis (on the right) in the diagram below.

As you can see, fructokinase uses ATP as a cofactor to convert fructose into fructose-1-phosphate. So if a large amount of fructose streams into the cell, it can deplete ATP right? Incorrect.

If we look a little further down, 1,3-Biphosphoglycerate conversion to 3-Phosphoglycerate creates an ATP. And a little further down, you generate another ATP by converting phosphoenolpyruvate to pyruvate. But for 1 glucose or 1 fructose molecule, that will be 2 ATP (check the diagram below).

Complete conversion of glucose to pyruvate generates 2 ATP (2 loss and 4 gain). Complete conversion of fructose generates 3 ATP (if all the fructose-1-phosphate goes to Dihydroxyacetone instead of also to Glyceraldehyde; which is not the case ofc.). But the point being is that despite the 1 loss of ATP at the start, it still gains 4 ATP back, which is more than glucose (since glucose loses 2 ATP). So no matter how fast fructose enters a cell, it can never deplete ATP unless someone has some serious mutations in glycolysis. And this excludes complete oxidative phosphorylation where pyruvate is converted to water and CO2 and creates 26 additional ATP.

So in summary, fructose actually generates more ATP than glucose. Quite the opposite of depleting ATP don’t you think?

But neither 100% of glucose nor fructose are ever completely converted to pyruvate as there are many side paths they can go. But the fact still stands that fructose doesn’t deplete ATP.

Please share this article with any fructose haters/conservatives you may know. 🙂

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4 Replies to “Fructose series part 1: fructose depletes ATP?”

  1. Good article. You should try to get Georgi on your YouTube channel.

    1. Thanks Luke,
      I plan on starting a podcast, but not sure when I’m actually going to get started on that.

      1. I think you do good work. Plz keep it up.

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