How We Actually Make Energy
Back to school for you!
Earlier this week, I found myself getting my tongue twisted trying to explain how a human actually makes energy from food.
Something something carbohydrate. Something something mitochondria. Something something electron transport chain.
And so I decided I would fully learn and understand how a human makes energy, including all of the steps and the additional pieces that are needed to get it from one step to another.
You see, if you didn't already know, when we produce energy from food, it doesn't just naturally go along a process.
We need things called cofactors to take it from one process to the next. And many times people are deficient in these cofactors and thus they can't produce energy productively.
Anyway, my goal with this post is to give you a thorough explanation of how a human takes food and turns it into actionable energy that they use to move, think, breathe, and exist.
Table of Contents
Step 1: Macronutrients & Digestion
Step 3: Into the Cells & Further Processing
Step 4: Onto the Powerhouse! Getting into the Mitochondria and Ready to Make Energy
Step 5: The TCA Cycle (Also called the Krebs Cycle or Citric Acid Cycle)
Fun fact - 99% of doctors don’t know you can actually test for leaks in someone’s TCA cycle.
Step 6: The Electron Transport Chain (ETC)
Bonus parts: Ketones & Methylene Blue
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Step 1: Macronutrients & Digestion
Energy in your body comes from the food you eat, which gets broken down into tiny parts to make a special energy battery called ATP.
Think of ATP like a rechargeable battery that powers everything from running to blinking!
Here’s how it works, your body uses three main types of food:
Carbohydrates like bread or fruits break into sugars like glucose & fructose
This is done in the mouth & intestines by an enzyme called Amylase
Fats like butter or oils break into fatty acids like stearic acid (which we like) and linoleic acid (which we don’t like)
This is done in the stomach & intestines by an enzyme called Lipase
You need bile to emulsify the fats which will make them accessible to lipases
You also need calcium to digest phospholipids
Proteins like chicken break into individual amino acids (and peptides) such as glycine or valine
Hydrochloric acid (stomach acid) unfolds proteins so that they can be broken up
This is done in the stomach & intestines by a protease enzymes and pancreatic enzymes
Zinc and Calcium are essential in this enzyme function
Step 2: Into the Blood
You can almost think that until food is absorbed in to the bloodstream, it is essentially still outside of your body. You can’t access it.
Here’s how we gain access to each piece:
Simple sugars like glucose are absorbed straight into the bloodstream
Fatty acids and monoglycerides are absorbed by intestinal cells and reassembled into triglycerides, which are then packaged into chylomicrons for transport in the bloodstream
Amino Acids move from the gut into the cells and then transported across the basolateral membrane into the bloodstream
Sodium (salt) is often used as a co-transporter
Step 3: Into the Cells & Further Processing
Okay, so we have our food that's broken down into these tiny pieces and it's running through our body in the blood. Now we need to get it into our cells, and after that, will be how we get it into the mitochondria.
Glucose enters cells using proteins called GLUT transporters (like GLUT1, GLUT2, GLUT4, etc.)
These transporters act like gates in the cell membrane. When glucose binds to the transporter, it changes shape and moves glucose from outside to inside the cell
Insulin (a hormone ketoers are afraid of) signals these cells to put more GLUT4 transporters on their surface, letting more glucose in after you eat
In your kidneys and intestines there is also a SGLT transporter which behaves the same way but requires sodium
Inside of the cell glucose is taken through a number of steps some of which are called glycolysis ultimately producing pyruvate
Glycolysis uses magnesium and NAD+
Fructose enters cells using specific transport proteins called GLUT5/GLUT2
This mainly happens in the liver
In the liver, fructose goes through a number of processing steps that require ATP (base unit of energy we’re trying to create) to get it into something called pyruvate
Excess fructose is turned into triglycerides (fat) in the liver
Triglycerides are packaged up as VLDL and sent into the bloodstream
This step requires choline
Most people are choline deficient
Chylomicrons & VLDL encounter another enzyme called lipoprotein lipase (LPL) when they reach muscle or fat cells which breaks them down into free fatty acids and glycerol
The free fatty acids released by LPL can now cross the cell membrane and this uptake is facilitated by fatty acid transport proteins
Long Chain free fatty acids inside the cell are “activated” to form fatty acyl-CoA
This step requires ATP (base unit of energy we’re trying to create) and Coenzyme A
Short Chain free fatty acids don’t require activation
Amino acids enter cells through specialized proteins in the cell membrane called amino acid transporters (just like glucose or fructose)
Some amino acid transporters use sodium, potassium or chloride to do their job
Step 4: Onto the Powerhouse! Getting into the Mitochondria and Ready to Make Energy
Funny story - I was under the impression until about 2 years ago, that mitochondria were theoretical parts of a cell that we’ve actually never seen - in the same way that physicists have theoretical particles.
Okay so we have the pieces we need inside the cell. Inside the cell is also the mitochondria. We need to get these pieces into the mitochondria so that they can make energy.
Here’s how we get them in:
Pyruvate (from carbs) is taken into the mitochondria via a specialized protein
Fatty acyl-CoA forms fatty acyl-carnitine using carnitine which obtained from diet or synthesized in the body
Most people are carnitine deficient
Short chain fatty acids cross the mitochondrial membranes directly-they do not require the carnitine shuttle or any specific transporter
This is why MCT oil or Coconut oil can be so powerful
Once inside the mitochondria they are activated to acyl-CoA using ATP and Coenzyme A
Amino acids can pass through the outer mitochondrial barrier without much restriction. The inner membrane is highly selective and impermeable to most small molecules, including amino acids. Specialized transporter proteins are required for amino acids to enter the mitochondrial matrix.
Here’s how we prep them for energy production:
Pyruvate is converted to acetyl-CoA by the pyruvate dehydrogenase complex
This requires Coenzyme A, Vitamin B1 (Thiamine), Lipoic Acid, Vitamin B2 and NAD+ (which comes from Vitamin B3)
Fatty acyl-CoA undergoes beta-oxidation to generate acetyl-CoA, NADH, and FADH₂
Amino acids are converted into acetyl-CoA and other TCA cycle intermediates (more on the TCA cycle later) via several different processes
This requires Vitamin B1, B2, B3, B5, B6, B7, B9, B12
Step 5: The TCA Cycle (Also called the Krebs Cycle or Citric Acid Cycle)
The TCA cycle (also called the Krebs cycle or citric acid cycle) is the main way your body turns food derivates into usable energy.
The main input as you might have noticed above is a molecule called acetyl-CoA.
The Main Steps:
Acetyl-CoA (2 carbons) joins oxaloacetate (4 carbons) to make citrate (6 carbons).
Citrate is rearranged and chopped up, releasing two carbon atoms as carbon dioxide (CO₂)-that’s the waste you breathe out.
As the cycle continues, the original oxaloacetate is re-formed, ready to start the cycle again with a new acetyl-CoA.
What Comes Out?
For each turn of the cycle, you get:
3 NADH (an “energy carrier” molecule)
1 FADH₂ (another energy carrier)
1 GTP or ATP (the cell’s direct energy currency)
2 CO₂
Why Is It Important?
NADH and FADH₂ carry high-energy electrons to the electron transport chain (another part of the mitochondria), where most ATP (energy) is made.
We explore the electron transport chain below
The TCA cycle is a “hub” for metabolism: it connects the breakdown product of carbs, fats, and proteins, (acetyl-CoA) and provides building blocks for other molecules your body needs
The TCA cycle is a repeating loop that turns the food you eat into energy your body can use.
It’s essential for life. If it stops, cells can’t make enough energy to survive.
The cycle itself requires a bunch of additional cofactors to run. Coenzyme A, Vitamin B1 (Thiamine), Lipoic Acid, NAD+ (which comes from Vitamin B3), Magnesium and Calcium.
Furthermore - if steps break or slow down due to external factors additional nutrients may be needed to plug the leak/fix the slow down. That is step dependent. The majority of people have inborn errors in the TCA cycle given our mishmash of genetics and the aggressive environment we now deal with.
Fun fact - 99% of doctors don’t know you can actually test for leaks in someone’s TCA cycle.
Patchwork is building rapid testing, interpretation and protocols to address someones energy production issues in the TCA cycle using something called an Organic Acids Test. You can join the waitlist here.
Use the invite code: Uncivilized to get a $100 discount on launch
Step 6: The Electron Transport Chain (ETC)
First off, if you've made it this far, congratulations to you. This gets more and more complex the further down you go and I've never really been able to put it all together until I wrote this post.
From step 5 we saw the critical output of each turn of the TCA cycle is 3 NADH and 1 FADH₂ molecule. These guys really make the energy that powers life.
The ETC uses high-energy electrons carried by NADH and FADH₂.
How does it work?
Electrons are dropped off:
NADH and FADH₂ deliver their electrons to the first protein complexes in the chain.
Electrons move down the chain:
The electrons are passed along a series of four big protein complexes (I, II, III, IV) and small carriers (like ubiquinone and cytochrome c).
Proton pumping:
As electrons travel through the complexes, energy is used to pump protons (H⁺ ions) from inside the mitochondria (the matrix) to the space between the membranes (the intermembrane space). This builds up a high concentration of protons outside the inner membrane.
Oxygen is the final electron acceptor:
At the end of the chain, the electrons combine with oxygen (which you breathe in) and protons to make water. Without oxygen, the chain stops.
ATP is made:
The protons want to flow back into the matrix (like water behind a dam). They rush through a special protein called ATP synthase, which uses this flow to make ATP from ADP-just like a water wheel making electricity
Each of the protein complexes has it’s own nutrient need but the critical cofactor that makes the ETC work is CoQ10 which carries electrons and protons up and down the chain.
Bonus parts: Ketones & Methylene Blue
Even in ketosis, the majority of the fuel that your body is burning is fatty acids, which we've already explained goes through fatty acid oxidation and then its own part of the TCA cycle. However, I want to mention how ketones work and also what methylene blue does in the context of how we make energy.
Ketones
Ketone bodies (mainly β-hydroxybutyrate and acetoacetate) are produced in the liver and transported to other tissues (like brain, heart, and muscle) during fasting, low-carb diets, or prolonged exercise.
Ketone bodies (acetoacetate and β-hydroxybutyrate) are small, water-soluble molecules produced in the liver mitochondria from fatty acids. Once made, they diffuse out of liver cells into the blood and are transported to other tissues (like brain, heart, and muscle)
When these tissues use ketones for energy, ketone bodies enter cells and cross the mitochondrial membranes without the need for carnitine.
In these tissues, ketones are converted into our old friend acetyl-CoA - And thus the story begins again as they enter the TCA cycle to produce energy.
Methylene Blue (MB)
Used by many bio-hackers and recently as part of the conversation now that the new HHS secretary was spotted taking this on a plane. Methylene Blue can act as a back up generator in energy production.
Bypassing Damaged Complexes
Normal ETC Flow: Electrons from NADH and FADH₂ travel through complexes I → III → IV, creating a proton gradient to make ATP.
Methylene Blue’s Role: If Complex I is damaged (e.g., in neurodegenerative diseases), MB accepts electrons directly from NADH and shuttles them to cytochrome c (bypassing Complex I). This keeps the ETC running smoothly.
Enhancing Complex IV Activity
MB donates electrons to Complex IV (cytochrome c oxidase), boosting its activity. This increases oxygen consumption and ATP production.
Example: In Alzheimer’s or Parkinson’s, where mitochondrial function declines, MB helps neurons maintain energy levels
Reducing Harmful Byproducts
Less Electron Leakage: By providing a direct path for electrons, MB minimizes “leaky” electrons that form reactive oxygen species (ROS) like superoxide radicals. Fewer ROS means less oxidative damage to cells.
Supporting Energy in Stressful Conditions
Cancer Cells: Tumors rely on inefficient glycolysis (Warburg effect). MB forces them back to oxidative phosphorylation, slowing growth.
Chronic Fatigue: MB improves ATP production in energy-starved cells, alleviating fatigue
Conclusion
Well, congratulations. You made it to graduation. If you read and understood any of this, I give you a B+.
Fundamentally, what I wanted to do in this post is explain that it's actually not that complex how we make energy.
There are a bunch of additional co-factors involved when we talk about vitamins and why we need to take them or choline and why we need to make sure we're getting enough.
It's important because we actually do need those things in making energy.
Oh there’s the bell… Class dismissed.
Want help?
At Patchwork we help people avoid diet & supplementation mistakes to achieve an optimal metabolism with personalized insights based on your DNA.
Not sure if we’re a good fit? Take the quiz