Ok nerds, every wonder how exactly creatine works to build muscle and to give you that extra push, pull, or crank?

While writing my most recent post where I shared my experiences starting creatine supplementation, part of my research took me on a tangent exploring exactly how creatine works at a cellular level to build muscle and increase training, and this turned out to be so interesting that I thought it merited a post by itself.  

How creatine works to build muscles is by boosting glycolysis and maing more ATP. Glycolysis image from Wikipedia. Creatine boosts glycolysis in muscle cells.

I did not think that my left-over Bio II knowledge of cellular respiration from 1998 would ever be put to use, but here we are.  Honestly, 17-year-old-me worked hard at memorizing the cellular respiration cycle, and surprisingly, it is still in my brain. 

Anyway, if you remember the basics of glycolysis, aka cellular respiration, from high school AP biology or a Bio II class, then you can actually understand the basic, and I mean basic, biochemistry of how creatine works to build muscle.   No fancy college biology knowledge required, and I should know, because I flunked those classes.  

If you want a nice little high school review of glycolysis, here is good old Khan Academy:

Glycolysis | Cellular respiration | Biology (article) | Khan Academy

There are two reactions that you will need to understand to know how creatine works: Glycolysis and what the Creatine Kinase enzyme does. We will look at each part of the process by itself, but the bottom line is this:

Bottom Line: Creatine builds muscle by increasing the threshold of ATP production in Muscle cells (Myocytes)

Lets begin with the end in mind and work back from there.  The bottom line is this: The more energy a muscle cell can generate the better, ATP is energy, and creatine helps a cell make more ATP.  But how?

Creatine works at the celular level in muscles. It is basicaly a loophole in the whole celular respiration/ATP generation process, and it does this through helping with glycolysis and through a reaction produced by the enzyme creatine kinase. Lets take a close look at glycolysis and the reaction produced by the enzyme creatine kinase. Then, we will put it all together.

Glycolysis: How all cells produce energy

Remember how glycolysis goes.  (Skim the Khan Academy page above or watch the videos if you need a refresher.) You need one molecule of glucose and 2 molecules of ATP to start.  One phosphate is removed from each of those ATP and added to that glucose molecule.  This yields one molecule of fructose and 2 molecules of ADP.  This molecule is unstable, and it splits into two different molecules which eventually convert into 2 ATP.  2 x 2 = 4.  Thus the yield for the whole process ‘costs’ 2 ATP but yields 4 ATP.  

But, did you know that when it comes to ATP production, our cells actually have a governor that stops the process.  A high concentration of ATP inhibits glycolysis, essentially placing a cap on a cell’s energy output.  (There is a reason for this, check out this page to learn why our cells turn off ATP production.) Of course, when our metabolism regulates the energy output of a cell in such a way, this limits the whole muscle’s training capacity. Sad.  

Creatine Kinase: How it works to boost cellular respiration and ATP production in muscle cells to build muscle

Here is a really cool video that I watched to learn about this enzyme process: creatine kinase.

Now, let’s understand the enzyme creatine kinase and what it does.  It is easy.  The creatine we ingest from our diets becomes creatine phosphate with the help of an enzyme called creatine kinase. Creatine kinase initiates the following reaction: one molecule of creatine takes a phosphate off a molecule of ATP, and the resulting molecules are ADP and creatine phosphate, a stable molecule.  Now phosphocreatine, a stable molecule, stores the phosphate, not ATP, an unstable molecule.  This benefits us in two ways.

The first benefit is that, we have less ATP, and cellular respiration chugs on without hitting the threshold and shutting down.  The second benefit is that, creatine phosphate can give its phosphate to ADP to make ATP. This means that when we are pushing out muscles to the limit and glycolysis hits the ATP threshold and slows down, creatine phosphate keeps making ATP. That right there is where your extra push, pull, or crank comes from.

From the website Biology Dictionary, this is the reversible reaction caused by the enzyme creatine kinase that when going from right to left, creates ATP. This is how creatine helps build muscle.

Where do we get creatine from and how much?

If you eat meat, you get creatine from your diet, so your body makes creatine phosphate from that.  However, unless you are having 16 oz steaks for breakfast, lunch, and dinner, with herring filet snacks in between, your cells aren’t creating enough creatine phosphate to increase the energy production potential of your muscle cells.

Scroll to the middle of this article to see exactly how little creatine you get from your diet. Again, unless you eat a ton of steak and herring everyday you are not getting much at all.

But, what happens when you supplement with 3-5 grams of creatine each day?  

First, you don’t have to eat 4 lbs of steak and herring every day, which is nice.  When we supplement, the concentration of creatine in our cells goes through the roof, and all of this creatine becomes creatine phosphate by the enzyme creatine kinase.  Because there are more creatine molecules taking phosphates off of ATP by creatine kinase, the concentration of ATP in the cells goes down, and cells never hit the threshold where ATP production stops.  Consequently, not only do we have more phosphates available to turn ADP into ATP but the cellular respiration engine also never slows down because the creatine is there to take phosphates off ATP ensuring that the glycolysis-stopping-threshold is never hit.  Cellular respiration is never inhibited by high concentrations of, and ATP production surges on.

In a Nut Shell: How does creatine work to build more muscle?

Creatine is like a two part escape clause that lets us get out of the restraints of cellular respiration. First, creatine holds on to phosphates (phosphocreatine) so cellular respiration is not shut down by a high concentration of ATP. Second, phosphocreatine can donate its phosphate back to ADT and make ATP. Consequently, a cell’s first method of making ATP is not restricted and a cell’s second method of making ATP is greatly increased. That is your extra push, pull, crank, or whatever you are demanding of your muscles.

Fun fact:  Your body makes about 65 kilos of ATP a day.  

This quote sums it up nicely:

“Given ample PCr (Phosphocreatine), the reaction from the enzyme creatine kinase regenerates ATP at a rate 40 times faster than oxidative phosphorylation and 10 times faster than glycolysis (Walliman et al., 1992). Phosphocreatine therefore acts as a quickly accessible “Swiss Bank account” for energy currency, allowing cells to “hide” ATP in an accessible form.”  https://www.sciencedirect.com/science/article/abs/pii/S0197018615300383

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