Ever since I started my ketogenic lifestyle I’ve been experiencing higher energy levels. Basically I have the same increased energy from the minute I wake up at ~7 A.M. up until I go to sleep at 2 A.M. at night. No post-prandial (after-meal) fatigue and no sleepiness during the day. It’s been quite amazing because during my entire life I was kind of suffering of moments of tiredness throughout the day.
As I began researching what happens inside the body under high-fat-very-low-carb nutrition, I wanted to know what could be the possible explanation of the higher energy levels. I’ve learned that carbohydrate metabolism yields lower amounts of ATP compared to beta-oxidation (fat metabolism).
It basically starts with glycolysis which has the purpose of converting 1 molecule of glucose to two molecules of pyruvic acids (pyruvates). Glycolysis yields 4 ATPs, but it requires 2 ATPs to be completed, so the net gain of energy is 2 ATPs.
After glycolysis, the 2 pyruvates react with Coenzyme A to form 2 molecules of Acetyl-CoA, which will later go into the TCA Cycle (Citric Acid Cycle or Krebs Cycle). In the TCA Cycle there are series of chemical reactions which lead to the release of more ATPs (yet, very decent amounts), CO2, CoA, and H+.
So far, we’ve only gained 4 ATPs, 2 from glycolysis and 2 from the TCA Cycle.
The next step is oxidative phosporylation or the Electron Transport Chain. This is where the hydrogen made available in the early stages of glucose metabolism will be oxidized. This is also where the most energy in the form of ATP is created. The ETC gives roughly 30 ATPs, yet there are 4 hydrogen atoms remaining which are released by their dehydrogenase into the chemiosmotic oxidation (in oxidative phosporylation). These 4 H+ give roughly 2 ATPs.
The total would be 38 ATPs for 1 molecule of glucose. Remember that glucose is a 6 carbon molecule (the black dots are the carbon molecules).
Some biochemistry textbooks say that 1 molecule of glucose yields between 36-38 ATPs. However, the amount of energy as ATP revolves around these numbers.
According to Guyton, 1 ATP has ~12,000 calories (12 kcals). Thus 38 ATPs would have 456,000 calories or 456 kcals.
However, the complete oxidation of each gram molecule of glucose releases 686,000 calories or 686 kcals.
This means that the efficiency of energy transfer in this case is 456/686 or 66%, while the remaining 34% of energy is released as heat. Let see what happens in fat metabolism.
If we took glucose (6 Carbon molecule) as an example in carbohydrate metabolism, let’s take palmitic acid (16 Carbon molecule) as an example in fatty-acid metabolism.
In order for a fatty acid to be metabolized, it needs to undergo three steps:
2. Transport from the cytosol into the mitochondrial matrix
1. The first step is the activation of the fatty acid. This is where the fatty acid is being added CoA to form the Fatty Acyl-CoA. The reaction uses energy (ATP) and it is performed under the action of thiokinase (a Fatty Acyl-CoA synthatase enzyme)
2. The second step is the transport of the Fatty Acyl-CoA from the cytoplasm into the mitochondrial matrix, so that it can undergo beta-oxidation. This transport is facilitated with the help of carnitine.
Basically Acyl-CoA is being attached carnitine and its CoA is removed. So it is an Acyl-Carnitine now, which gets inside the mitochondrial matrix from the cytosol through carnitine acyl-transferase I.
Once inside the matrix Acyl-Carnitine dumps carnitine and it gets its CoA back. Carnitine is shuffled back into the cytosol through carnitine acyl-transferase II, where the same process would start all over again.
So now we have the Acyl-CoA in the mitochondrial matrix and the beta-oxidation process can take place.
3. The third step is beta-oxidation where Acyl-CoA is dehydrogenated and undergoes a series of oxidation and hydration reactions to create Acetyl-CoA, which will further be able to enter the TCA Cycle.
This is a repetitive process and its length depends upon the length of the fatty acid that is metabolized. Every time Acyl-CoA enters the process it will have 2 fewer carbons and these reactions undergo up until there are no more carbons left. Here’s a quick video that would make you understand it better:
In the case of palmitic acid we have 16 carbons (even number), but if the number of carbons is odd, the oxidation process occurs until there are three carbons left. Then, several reactions take place to create Succinyl-CoA which can also further enter the TCA Cycle.
For palmitic acid, there is an even number of carbons (16) so the process of beta-oxidation is:
It may be difficult to grasp it but see this as a continuous process where every instance of the process has the purpose of removing 2 carbons (which is why the “beta” name) and undergo the subsequent oxidation and hydration reactions to get to Acetyl-CoA (goes to TCA Cycle) and Acyl-CoA (with 2 fewer carbons) which will go into the process again.
Here’s another perspective:
In the case of our 16 Carbon Palmitic Acid we have 7 rounds of beta-oxidation. As you can see, besides Acetyl-CoA, the whole process yields FADH2 and NADH, which will further be used for energy production in the TCA Cycle and in the ETC.
Energy Yield of Palmitic Acid (16C)
8 Acetyl-CoA (1 for each round + the remaining from the last two carbons)
Each Acetyl-CoA yields 12 ATPs, thus 8 Acetyl-CoA will yield 96 ATPs. Each FADH2 yields 2 ATPs (some biochemistry textbooks assume it yields 1.5 ATPs), while each NADH yields 3 ATPs (some biochemistry textbooks assume it yields 2.5 ATPs). So:
8 Acetyl-CoA x 12 = 96 ATPs
7 FADH2 x 2 = 14 ATPs
7 NADH x 3 = 21 ATPs
The total energy yield is 131 ATPs, but the activation of the fatty acid (step 1) requires 2 ATPs so the net yield of energy is 129 ATPs for a molecule of palmitic acid (16 carbon).
Besides, longer chain fatty acids yield even more energy. For example, an 18 Carbon fatty acid (stearic acid) yields 146 ATPs, while a 20 Carbon fatty acid will yield 163 ATPs. Compare that to the 36-38 ATPs that are generated by the oxidation of 1 molecule of glucose. Talk about nutrient dense foods.
Remember that I’ve told you about the energy efficiency of glucose which is 66%. The energy release when 1 molecule of glucose is burned is 686 kcals.
Glucose has a molecular weight of 180g/mole. The amount of ATP generated from 1 molecule of glucose is 38 ATPs, which yields 456 kcals.
So, when burning 1 molecule of glucose, we only use 66% (456/686) from the energy released from it as ATP, while the rest of 34% is energy released as heat.
Conversely, Palmitic acid (16C) has a molecular weight of 256g/mole. Burning it would release 2550 kcals. The amount of ATP generated from 1 molecule of palmitic acid is 129 ATPs, which yields 1548 kcals (129*12). In this case, if we divide 1548/2550 we get 60%, which is the amount of energy transferred to ATP by metabolizing 1 molecule of palmitic acid. The rest of 40% is released as heat.
So, we have more ATP and more energy released as heat for 1 molecule of a fatty acid compared to 1 molecule of glucose. However, molecular weight difference should be considered, but even so, the release of energy is far greater (129 ATP vs. 38 ATP) between these types of macronutrients. I guess this contributes to the higher energy levels that I experience as part of my high-fat nutrition besides other factors (lower oxidative stress). I’ve been detailing them in the upcoming book (see below for details).
If something is unclear or if you want to add something, shoot me a comment in either of the sections below.
1. Guyton, C. & Hall, J. E. (2010). Medical Physiology. Saunders.
2. Stoker, S. (2006). General, Organic, and Biological Chemistry. Cengage-Learning.
3. Darvey, I. G. (1998). How does the ratio of ATP yield from the complete oxidation of palmitic acid to that of glucose compare with the relative energy contents of fat and carbohydrate?. Biochemical Education, 26(1), 22-23.
4. Meltzer, V., Pincu, E., & Cristescu, G. (2007). Heat of Combustion of some saturated dicarboxylic acids from group contributions. gas, 2, 4.
5. Lodish, H. Berk, A., Zipursky S. L., Matsudaira, P., Baltimore, D. & Darnell, J. (2000). Molecular Cell Biology. W. H. Freeman, New York.
6. Krisnangkura, K. (1991). Estimation of heat of combustion of triglycerides and fatty acid methyl esters. Journal of the American Oil Chemists Society, 68(1), 56-58.
Photos: here, here, here, here and here