Chris Trejbal, CNP, NNCP, PTS

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Remember that Krebs guy?

Recently my wonderful fiancée asked me to explain glycolysis, the Krebs cycle and the electron transport chain (ETC).

Remember any of that from biology class? I barely did, despite having taken copious amounts of anatomy and physiology and biochemistry. Upon explaining, I found it EXTREMELY helpful to have diagrams. So, below are some excellent photos to help explain how we make ATP- the energy currency in the body.

Step 1- Glycolysis

Let’s jump right into it. We can see in a simplified way how we take the glucose we eat from food and turn that 6-carbon chain into 2 pyruvate- 2x 3 carbon chained molecules. Why is this step necessary? Because we need that sweet, sweet acetyl-CoA as our golden ticket into the Krebs cycle, and making pyruvate is our step to getting there. We can also get to lactic acid fermentation from here, but that’s for another time. 

Cool fact- See in green the NADHs? Those are actually made from niacin. Yes, that’s vitamin B3. We’ll see along the way how certain vitamins and minerals play a crucial role in energy production. 

Step 1.5- Transition Reaction

This intermediary step is often forgotten, but I consider it quite important! First, it shows you how we get from pyruvate to acetyl-CoA. This is also where coenzyme A is essential and where vitamin B5 (pantothenic acid) plays a role in energy production. Finally, as seen by the H+, we have hydrogen being built up for later.  

Coenzyme A

There it is! Look at you go, pantothenic acid. Another cool fact is that acetyl-CoA can be synthesized from glucose, ketone bodies, and fatty acids. Yes, for those who are fat-adapted, AKA deriving their energy from fat instead of carbs, this is where your ketones are converted into acetyl-CoA and turned into energy. 


Step 2- The Krebs cycle (AKA the citric acid cycle or CAC)

Whether we eat primarily carbs or fats, we’ve got the golden ticket: acetyl-CoA. Now, we can start our journey through the Krebs cycle. Get ready…

General view of the Krebs cycle

I’m sure most people look at this thing and ask themselves: just why? Why does energy production need to be so complicated and involve cycles? Well, I think you’re right. However, this cycle does a heck of a lot more than produce energy. So let’s focus on that first before seeing what else it can do. 

Now that we have 2 acetyl-CoA molecules from 2 pyruvates let’s hop on the Krebs cycle. There’s a lot going on here in the photo, but let’s concentrate on NADH and FADH. As we mentioned earlier, we are building up hydrogen atoms. Every time we pass a step in the Krebs cycle (labelled 1 through 8), we add to this build-up for the next step in the electron transport chain (ETC)- ATP production. ATP in the ETC…see, it rhymes, so it must be true!

What else goes on in the Krebs cycle? 2 cool facts.

1. Notice the FADH in the general view of the Krebs cycle? FADH, AKA flavin adenine dinucleotide contains, you guessed it- riboflavin, or vitamin B2. There it is on the left! 

2. Amino acids have a carbon skeleton that gets cleaved off from the amine group. Some of those enter the Krebs cycle and act as constituents for those intermediates (labelled 1 through 8). Pretty cool! Here’s and example of what amino acid skeletons go where:

Amino acid participation in the Krebs cycle

Step 3- The electron transport chain (ETC)

Okay okay okay, so what does the ETC look like? I’m glad you asked.

Voila! This is where the magic happens. This is where we’ve taken all of our stored hydrogens and are ready to put them to work. 

See how all of that NADH and FADH lose their hydrogen atoms? Through those red potato-looking structures wedged in the inner mitochondrial membrane, those guys carry electrons across the membrane, where hydrogen crosses into the intermembrane space. The golden line going across is the flow of electrons across the membrane. 

Another cool fact- those complexes (I, II, III, IV) contain iron-sulphur-based protein. The Q (hidden by the line) is ubiquinone, AKA CoQ10, which is reduced to ubiquinol, its active form. Another molecule we obtain from the diet that is often supplemented. Hence why we need to eat a varied diet containing foods like red meat, organ meats, some fortified cereals, and some legumes to get adequate iron. CoQ10 is found at high amounts in beef & chicken heart and other organ meats, as well as peanut, sesame, and sunflower oil, soybeans, and more. 

Back to making ATP. Now that we have a bunch of hydrogen atoms in the intermembrane space, they create an electrochemical gradient. They’re ready to move downhill back into the mitochondrial matrix. And when they do, oh boy, it’s ATP synthase time. ATP synthase is like the turbine that takes those hydrogen atoms (that are ready to move downhill in this photo) and turns ADP into ATP. Boom. Energy. If you’re interested, this process is called chemiosmosis,  which refers to any process where energy stored in a gradient is used for something. In our case, to make ATP. 

How much ATP have we made?

After heading through glycolysis, the transition reaction, the Krebs cycle and the ETC, the ‘on paper’ number of ATP created is 36-38. I’ve decided not to tally up the ATPs/NADHs/FADHs because this number varies depending on where you look. This was meant to be a broad overview. Finally, below is yet another photo of the entire cradle-to-grave process behind cellular respiration (as I mentioned above, lactic acid fermentation is a topic for another time).

Overview of cellular respiration

I also made this because sometimes you need that one person (or online source) for something to really click in. Even though a dozen people have tried to explain something one way, you come across a photo or video where everything makes sense. So I hope to have done this for you.

References

Coenzyme A - an overview | ScienceDirect Topics

β-hydroxybutyrate and ACA are utilized as fuel molecules in all... | Download Scientific Diagram (researchgate.net)

Ubiquinol is superior to ubiquinone to enhance Coenzyme Q10 status in older men - Food & Function (RSC Publishing)

Krebs / citric acid cycle (video) | Khan Academy

Oxidative phosphorylation | Biology (article) | Khan Academy

https://www.tandfonline.com/doi/abs/10.1080/10408390902773037

(Photos are clickable to their respective web page)