Aerobic Glycolysis: How An Increased Demand For NAD+ Can Boost It

Aerobic Glycolysis: How An Increased Demand For NAD+ Can Boost It

A recent study sheds light on aerobic glycolysis and cellular proliferation. Read on to learn more. 

 

In this article:

  1. What Is Glycolysis?
  2. What Is Aerobic Glycolysis?
  3. What Did The Researchers Do?
  4. What Were the Results of Their Experiments?
  5. What Did They Discover About Aerobic Glycolysis?

Understanding Aerobic Glycolysis in Proliferating Cells

What Is Glycolysis?

Glycolysis is a metabolic pathway. This pathway involves the conversion of food into energy. Cells use the energy released from glycolysis to make: 

  • Adenosine triphosphate (ATP) 
  • Nicotinamide adenine dinucleotide (NADH). 

ATP is a molecule that stores and transfers energy for different cellular processes. On the other hand, when NADH is oxidized, it becomes NAD+. NAD+ helps transport electrons to the cell's mitochondria. This helps turn nutrients into energy.

The presence or absence of oxygen can impact metabolic processes. When oxygen is available, most cells reduce oxygen to water through respiration. Respiration supports the oxidation reactions cells use to extract energy from nutrients.

Cells use an alternative metabolic process when there isn't enough oxygen available. Instead of respiration, most cells will ferment carbohydrates.

The fermentation process in cells creates lactate or ethanol. Cells use lactate and ethanol to help extract energy from nutrients.

Some rapidly proliferating cells use the fermentation process even if there is more than enough oxygen present. This metabolic phenotype is Aerobic glycolysis. 

 

What Is Aerobic Glycolysis?

Aerobic glycolysis is a type of glycolysis. It is a cellular condition where glucose converts to lactate in the presence of oxygen. It is also called the Warburg effect.

The Warburg effect is more commonly associated with tumors and cancer cells. However, it is also present in non-cancer cells. For example, yeast cells, bacteria cells, lymphocytes, and fibroblasts engage in aerobic glycolysis. 

There are a few non-proliferative cells that also engage in aerobic glycolysis, such as pigmented epithelial cells in mammals' eyes.

Even though a variety of cells engage in aerobic glycolysis, researchers cannot fully explain its mechanisms. They also don't completely understand how it relates to cellular proliferation. 

Researchers ran a series of experiments on yeast and mammal cells to understand aerobic glycolysis better. They examined the consequences of increasing mitochondrial oxidation in cells.

 

What Did The Researchers Do?

Acetyl-coA biochemical, molecular model. Atoms are represented as spheres with conventional color coding | What Did The Researchers Do? | The Role Of HDAC4 In Maintaining Epigenome Identity

Through a series of experiments, the researchers suppressed fermentation in cells. To do this, they increased pyruvate dehydrogenase complex (PDH) activity in cells. PDH is a multi-enzyme that catalyzes the transformation of pyruvate to acetyl-CoA.  

Acetyl-CoA plays a delivery role that facilitates the Krebs cycle. So PDH plays a vital role in regulating aerobic glycolysis in cells. 

 

What Were the Results of Their Experiments?

After running their experiment, the researchers found:

  • PDH activation limits aerobic glycolysis and cellular proliferation. 
  • PDH activation decreases NAD+/NADH in ratios in cells, so it decreases cellular proliferation.
  • Increasing pyruvate oxidation limits NAD+ availability for the oxidation reaction. This impairs the proliferation of cells. 
  • Altering NAD+/NADH impacts PDH activation, so it impacts cellular metabolism. 
  • They can restore cellular proliferation by regenerating NAD+ (even after activating PDH). 
  • Reducing NAD+/NADH ratios impede mitochondrial electron transport and NAD+ regeneration. 
  • NAD+ regeneration is more dependent on mitochondrial complex when PDH is activated. 
  • When pyruvate dehydrogenase kinases (PDK) is inhibited, excess ATP limits NAD+ regeneration. 
  • In proliferating cells, NAD+ regeneration demands can supersede the ATP requirement. 
  • Separating ATP synthesis and electron transport increases NAD+ regeneration through respiration.
  • When PDH is activated, increasing ATP consumption decreases cellular proliferation.
  • NAD+ availability in cells determines aerobic glycolysis in cells.  
  • Giving cells another way of regenerating NAD+ suppresses aerobic glycolysis in yeast and mammal cells. This alternative way of regenerating NAD+ doesn't impact cellular proliferation. 

Overall, the findings suggest that aerobic glycolysis occurs when the demand for NAD+ is more than the demand for ATP. Oxidizing pyruvate (rather than fermenting it), increases the demand for NAD+ regeneration. This regeneration happens through mitochondrial respiration.  

 

What Did They Discover About Aerobic Glycolysis?

Aerobic glycolysis is a cellular process seen in many species, so it is essential to understand the conditions that trigger it. Maintaining a high AT/ADP ratio is essential for the survival of many cells. That is why the oxidation of nutrients is linked to ATP production. 

Mitochondrial respiration can't keep up with NAD+ regeneration when the demand for NAD+ is more than the demand for ATP. This triggers aerobic glycolysis. 

NAD+ plays a vital role in cells. It helps cells create the energy they need for optimal functioning. Some researchers also believe that NAD+ levels can impact aging because its levels decrease as you age. 

Understanding the role of NAD+ in aerobic glycolysis is useful in the field of epigenetics. If you are interested in learning more about the science of aging and epigenetics, visit the Tru Diagnostic website today.

 

What do you think of these new findings? Share your thoughts with us in the comments section. 
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