The cycle of turning fats into BHB, and then BHB into energy, involves two processes:

Ketogenesis: The production of BHB in the liver. It means ketone (keto-) generation (-genesis).

Ketolysis: The process of transforming BHB into ATP (the energy currency of the cell). It means ketone (keto-) breakdown (-lysis).

Both mechanisms involve complex chemical processes which are condensed below:

STEP #0: MAKING FREE FATTY ACIDS (LIPOLYSIS)

Before BHB production begins, stored fat needs to be converted into free fatty acids.

Lipolysis is the process of turning triglycerides — stored in fat tissue — into glycerol and free fatty acids (FFA) that enter the blood and travel to the liver to be turned into BHB.

PROCESS #1: KETOGENESIS

Where: The mitochondria of liver cells

Result: BHB

BHB production happens in the mitochondria of liver cells (what is commonly known as the powerhouse of the cell), and it follows these steps:

#1. Fatty acid activation (acyl-CoA): Before they’re able to cross the mitochondrial barrier, long-chain fatty acids need to be “activated” because the mitochondria only accepts short-chain fats. A molecule called Coenzyme A (CoA) is attached at the end of the fatty acid, and this combo is called acyl-CoA.

#2. Fatty acid oxidation (acetyl-CoA): Once inside the mitochondria, acyl-CoA is broken down into acetyl-CoA. This a crucial molecule because it’s the only one that can enter the Krebs Cycle:

#3. Krebs Cycle: Also known as the citric acid cycle (CAC) or tricarboxylic acid (TCA) cycle. This is the process that generates ketones and precursors of amino acids by breaking down acetyl-CoA. It works by fully oxidizing all molecules to carbon dioxide (CO2). The process for making BHB goes like this:

Acetyl-CoA

Acetoacetyl-CoA: acetyl-CoA degrades into acetoacetyl-CoA.

HMG-CoA: Acetoacetyl-CoA degrades into HMG-CoA.

Acetoacetate (AcAc): HMG-CoA turns into the first ketone, AcAc.

BHB: AcAc is reduced to BHB, and acetone is produced as a by-product.

PROCESS #2: KETOLYSIS

Where: The mitochondria in cells of other organs except the liver

Result: ATP

Once BHB is released (ketogenesis), your heart, brain, and other organs absorb it to turn it into ATP — the energy currency. It will go through the Krebs cycle again, just a little differently:

#1. Absorption by organs: When BHB is in the bloodstream, your organs — except your liver — take it up for energy. Ironically, the liver doesn’t have the ability to utilize ketones even though it makes them.

#2. Turning BHB back to acetyl-CoA: BHB has to turn back into acetyl-CoA because it’s the only molecule that can go through the Krebs cycle, remember? So, when BHB enters other organs, it retraces the steps it first took in the liver:

BHB

Acetoacetate (AcAc): BHB turns back into the first ketone.

Acetoacetyl-CoA: Acetoacetate (AcAc) is turned back to this molecule.

Acetyl-CoA: Acetoacetyl-CoA turns back to acetyl-CoA, which can enter the Krebs cycle.

#3. Krebs Cycle: Acetyl-CoA completely oxidizes in the cycle, and this oxidation releases electrons into two carrier molecule: NADH or FADH2.

#4. Oxidative phosphorylation (aka ATP creation): The electrons from NADH or FADH2 are transferred towards O2, which creates ATP. This is also called the mitochondrial respiratory chain.

As you can see, using BHB for energy is an intricate process. Basically, acetyl-CoA can turn into BHB (in the liver), and then BHB has to turn back into acetyl-CoA to make usable energy (ATP in organs).

In summary, BHB is created in the liver by oxidizing fats (ketogenesis). Then BHB is turned into ATP (energy) through oxidation in organs (ketolysis).

Running on BHB gives you a metabolic advantage over glucose.