Fat Metabolism: Analyzing KEEG Pathways

The microbiome opens the pathway to understanding how the body works more and more every day. With a Thryve Gut Test, we have the ability to analyze your DNA and look deep into many physiological functions carried out by your system on a molecular level. This is even more important when it comes to fat metabolism. Thanks to these advancements in technology and following KEGG pathway maps, we can determine how efficiently your body metabolizes fats (lipids) to produce energy, control weight, and promote cognitive function. Let’s take a look at the biomarkers for fat metabolism and how Thryve Inside can help you feel your best!

What is Fat Metabolism?

Fats aren’t as bad as
we make them sound

Fat metabolism (or lipid metabolism) is more than just burning off excess pounds around the gut.

There is far much more to fats than pounds on a scale. In fact, they’re not as evil as the mainstream makes them out to be.

Healthy fats are essential for human functioning, including building muscle, maintaining brain health, and absorbing nutrients.

The process of creating fats, breaking them down for energy, getting rid of waste, and recycling nutrients are all part of fat metabolism. These metabolic processes cover consuming fats in your diet or creating them yourself.

Fatty Acid Biosynthesis

Avocado love

Fatty acids are generated within our liver. That’s where our liver processes carbohydrates and introduces them to a litany of enzymes. Depending on these interactions, we get 12 nonessential amino acids. The other eight aren’t products of fat metabolism [1]. Instead, they must be consumed through diet.

Fatty acid biosynthesis is reliant on carbohydrate metabolism. When our digestive system breaks down foods to simpler sugars, it can produce a wide array of beneficial enzymes and cofactors. A couple of these chemicals are acetyl coenzyme A (acetyl-CoA) and Nicotinamide adenine dinucleotide phosphate (NADPH).

When acetyl-CoA and NADPH interact with a group of enzymes known as Fatty acid synthase (FAS), it kicks off the fatty acid biosynthesis process inside the cytoplasm and endoplasmic reticulum of cells.

Acetyl-CoA and Fatty Acid Production

First, the body takes two acetyl-COA. One of these coenzymes gets introduced to a carboxylic acid and the enzyme acetyl-CoA carboxylase (ACC). ACC is the primary enzyme that’s necessary for all fatty acid creation [3].

The spare acetyl-CoA and newly formed malonyl-CoA lose their CoA. A carrier protein by the name of acyl-carrier protein (ACP) fills the void. When ACP enters the fold, the new molecules become acetyl-ACP and malonyl-ACP, respectively.

NADPH and Fatty Acid Reduction

One of the primary responsibilities of fat metabolism is to produce energy to store for later. This backup reserve is known as ketones. They get stored in the liver and are secreted when we are missing out on carbohydrates to break down for simple sugars to create energy. When this happens, it’s known as ketosis.

In this portion of fat metabolism, ketones get hydrolyzed by the enzyme NADPH. NADPH is a reducing agent in fatty acid production [2]. It helps strip molecules that allow other enzymes and cofactors to make a difference.

With NADPH in the picture, water gets removed from the newly hydrolyzed new molecule and hydrogenated to make a saturated fat intermediate. As malonyl-ACP enters the equation, an intermediate fat with 16 carbons is created. This newly chained fat will serve as a prototype for many fatty acids.

Fatty Acid Elongation

Fatty acids that extend beyond 16 carbons typically transpire within the endoplasmic reticulum. The endoplasmic reticulum is an integral organelle within eukaryotic cells. These are cells with a true nucleus. Therefore, eukaryotic cells support the life of humans, fungi, and plants.

On the other side, archaea and bacteria have prokaryotic cells. These cells don’t have a nucleus. However, prokaryotes and eukaryotes both are responsible for similar functions, including protein and fat synthesis, all while serving as hosts for DNA.

long-chain fatty acids fat metabolism
Pilin’ on the carbon!

For 16-carbon molecules to become elongated, they must interact with enzymes within the endoplasmic reticulum. These enzymes are called elongases.

While most fatty acid elongation happens inside the endoplasmic reticulum, it also transpires in mitochondria [4]. Mitochondria serves as the digestive system of a cell. This realization is fascinating because our probiotic bacteria also make short-chain fatty acids, such as butyrate. This healthy fat is essential for the health of our digestive system.

The most significant difference between fatty acid synthesis in the cytoplasm and mitochondria (or endoplasmic reticulum) is that the latter uses CoA to attach to the manonyl. As we mentioned earlier, the cytoplasm pathway uses ACP.

Fatty Acid Degradation

This portion of fat metabolism is when our body breaks fatty acids into their simpler metabolites. When it’s all said and done, fatty acid degradation will result in acetyl-CoA. This coenzyme will be then be used in the Citric Cycle of carbohydrate metabolism.

To begin this portion of fat metabolism, the metabolites get stored in our fat tissue (adipose cells). Inevitably, we burn off these fats by exercise and intermittent fasting. This process is known as lipolysis.

intermittent fasting for gut health
The benefits are real

During lipolysis, free form fatty acids are released into the bloodstream and used to power our cells. During their travels, the free form fatty acids will interact with fatty acyl-CoA synthetase. After this enzyme causes a chemical reaction, it will then become introduced to adenosine triphosphate (ATP). ATP is like currency for our cells, giving them the power and incentive to carry out their functions.

During this meeting, the α-phosphate compound loses an electron. This transfer of electrons causes two new phosphate molecules — pyrophosphate and acyl-chained Adenosine monophosphate (AMP). The acyl chain then creates an activated bond with CoA. Now, the fatty acid is ready to be oxidized by the cell.

Once this happens, the fatty acids become 2-carbon acetyl-CoA molecules. These simpler compounds enter the Citric Acid Cycle. This entry generates lower levels of Nicotinamide adenine dinucleotide (NADH) and
Flavin adenine dinucleotide (FADH2). These are coenzymes that can be used in many metabolic processes and are pivotal for the production of more ATP.

Synthesis and Degradation of Ketone Bodies

As we noted, exercise and intermittent fasting can cause lipolysis. The body fat that gets burned off is called triglycerides. Usually, these compounds are used as cholesterol indicators. They are our backup reserve for when we don’t consume carbohydrates in our diet to promote gluconeogenesis.

Burn ketones, burn fat

During this part of fat metabolism, the triglycerides get introduced to water in our system. This interaction causes the triglycerides to become hydrolyzed, breaking them off into free form fatty acids.

Fatty acids get activated within the cytosol and shipped off the mitochondria. Here, beta-oxidation occurs. The end result is Acetyl-CoA. This much simpler coenzyme then makes its way to the liver, where it promotes the production of ketone bodies. All-natural energy powered by ketones is the primary objective of ketosis.

Once the ketones are used, they are recycled back into Acetoacetyl-CoA. This coenzyme is now free to enter the Citric Cycle.

Analyze Your Fat Metabolism

Not sure you’re burning fat adequately, or not producing enough energy to power you through the day? There might be something off with your fate metabolism. The best way to find out if this is happening is to get your gut tested. Using KEGG pathways, we can map out where the deficiencies are. That way, we can get your gut health on the right track. From there, you will shed excess weight and produce energy that will have you looking good and feeling good!

Thryve Probiotics Gut Health

Resources

[1] Hou, Y., Yin, Y., & Wu, G. (2015). Dietary essentiality of “nutritionally non-essential amino acids” for animals and humans. Experimental biology and medicine (Maywood, N.J.)240(8), 997–1007. https://doi.org/10.1177/1535370215587913.

[2] Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21154/.

[3] Parvy, J. P., Napal, L., Rubin, T., Poidevin, M., Perrin, L., Wicker-Thomas, C., & Montagne, J. (2012). Drosophila melanogaster Acetyl-CoA-carboxylase sustains a fatty acid-dependent remote signal to waterproof the respiratory system. PLoS genetics8(8), e1002925. https://doi.org/10.1371/journal.pgen.1002925.

[4] Kastaniotis, Alexander J, et al. “Mitochondrial Fatty Acid Synthesis, Fatty Acids and Mitochondrial Physiology.” Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids, U.S. National Library of Medicine, Jan. 2017, www.ncbi.nlm.nih.gov/pubmed/27553474.