Nucleotide Metabolism: Analyzing KEGG 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 nucleotide metabolism. Thanks to these advancements in technology and following KEGG pathway maps, we can determine how efficiently your body metabolizes nucleotides to make DNA and RNA. Let’s take a look at the biomarkers for nucleotide metabolism and how Thryve Inside can help you feel your best!

What is Nucleotide Metabolism?

Nucleic acids are essential for the production and degradation of DNA and RNA. These important molecules are comprised of a cluster of nucleotides. All of the components that create a nucleotide polymer are created during the carbohydrate metabolism process.

From there, the body uses simplified sugars to see the nucleotide metabolism process through. That way, our body has the genes necessary to keep our family lineage going, facilitate energy metabolism, and maintain our overall health.

Types of Nucleotides

While there are five types of nucleotides [1]. Typically, these compounds are produced in the liver. They are dependent on the nitrogen base that forms the nucleotides’ structure. Nuts and bolts, all nucleotides consist of three main components:

nucleotide metabolism
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  • A Nitrogenous Base (Adenine, Guanine, Cytosine, Thymine, Uracil)
  • A 5-Carbon Sugar (Either D-Ribose or D-Deoxyribose)
  • A Phosphate

Nucleotides are given their names based on the simple nitrogen and number of phosphates. Let’s take the most significant catalyst for energy, adenosine triphosphate (ATP).

As the name implies, ATP is an adenine-based molecule. With the name triphosphate, ATP has three phosphate molecules. While it holds no bearing on the name, ATP contains D-Ribose. Cue the “More You Know” rainbow!

Nucleotide metabolism commences when the compound interacts with an enzyme known as Phosphoribosyl pyrophosphate (PRPP) [2]. What happens next depends on the particular nucleotide. That’s because there’s two different paths a nucleotide can take during nucleotide metabolism.

Purine Metabolism

While there are five classified nucleotides, these compounds can be broken into two distinct groups. Both go through different nucleotide metabolism processes. Which pathway they go down is dependent on the nitrogen base. Adenine and guanine are classified as purines.

Purine Synthesis

For purine to produced, PRPP must be converted into inosine monophosphate (IMP). This process requires many essential nutrients and proteins to transpire.

Namely, the conversion of IMP requires:

  • Amino Acids (Aspartate, Glycine, Glutamine)
  • 6 ATP
nucleotide metabolism
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The ATP in the formula helps create Guanosine triphosphate (GTP) [3]. As you remember, guanine is one of the nucleotides mentioned above. GTP and ATP help stimulate each other’s production. So, they autonomously keep one another in check, so your body has enough of these essential catalysts to carry out nucleotide metabolism processes.

Thanks to GTP, IMP can convert to adenosine monophosphate (AMP), a simpler derivative of ATP. Subsequently, AMP can promote the production of guanosine monophosphate (GMP). Keeping these two purines in balance is essential. Otherwise, you can develop DNA mutations [4].

Purine Catabolism

To see the nucleotide metabolism through, you can’t just rely on synthesizing compounds. Your body must break them down. Purines also go through a different nucleotide catabolism than their three counterparts.

During this process, your liver uses enzymes to break the purines down to uric acid. The 5′-nucleotidase enzyme in our liver will use up the phosphate. This process will strip the nitrogen away from the nucleotide. Each will go on a slightly different path.

Adenine Degradation

Water/blood start the degradation process

On its own adenine becomes deactivates and vulnerable. When it comes into contact with water in our system, adenine becomes hyrolyzed, producing hypoxanthine. This transformation is made possible by adenosine deaminase [5].

Adenosine deaminase is an enzyme that helps the body break down adenine from food. So, the circle of life continues thanks to our nucleotide metabolism.

When oxygen comes into the mix, hypoxanthine inevitably turns into uric acid. We expel uric acid through our waste, completing the purine catabolism process.

Guanosine Degradation

Without its phosphate, guanosine becomes guanine. Once hydrolyzed, this compound interacts with the enzyme guanine deaminase. This kickstarts the metabolic processes that converts this nitrogen into uric acid, which gets dispelled from the system.

Pyrimidine Metabolism

This part of nucleotide metabolism involves cytosine, thymine, and uracil. Pyrimidine compounds go through many of the same nucleotide metabolism benchmarks as purines. However, they pull the show off with a different cast of characters. Let’s take a look.

Pyrimidine Production

All pyrimidines require many of the same chemicals to pull off their metabolic processes.

Pyrimidines require:

  • Amino Acids (Aspartate, Glutamate)
  • Bicarbonate
  • 2 ATP

Once this polymer is formed, it interacts with PRPP. This is where PRPP will introduce a ribose-monophosphate (RNA) to the polymer. Here lies the significant difference between purine and pyrimidine synthesis. The sugar is added after everything is formed. Whereas, purines need the carbohydrate to form the polymer in the first place.

Introducing a phosphate causes the pyrimidine to become uridine. The uridine interacts with the 2 ATP to create uridine-triphosphate (UTP) [6].

UTP gets together with the nitrogen base to make:

  • Cytidine-Triphosphate (CTP)
  • Thymidine
  • Deoxyuridine

Uniquely enough, you need ATP (a purine) to start this metabolic process. Furthermore, CTP stops pyrimidine synthesis from transpiring [7]. This counterbalance helps keep purine and pyrimidine as equal as possible. Maintaining this balance is essential for DNA production.

Pyrimidine Catabolism

Much like purines, pyrimidines do their own thing, too. There are two different processes that these three nitrogen bases will go through.

Cytosine and Uracil Degradation

The recycling of uracil and cytosine are similar. They converted into the amino acid, beta-alanine. Inevitably, this becomes malonyl-CoA [8]. Malonyl-CoA is a coenzyme necessary for fatty acid production. Seeing as we need amino acids for nucleotide metabolism to happen, this recycling process is pivotal.

Thymine Degradation

Thymine goes down a different path. First, it becomes the byproduct, beta-aminoisobutyric acid, before being used to produce methylmalonyl-CoA [9]. Other carbon molecules are left behind, which get used during our Citric Cycle. In the end, our body is left with ammonia, water, and carbon dioxide.

Analyze Your Nucleotide Metabolism

Want to make sure your genetics remain healthy enough to pass onto future generations? 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 produce DNA and RNA that will set the path for healthy generations to come!

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Resources

[1] Helmenstine, Anne Marie. “The 5 Kinds of Nucleotides Are Polymers Made Up of 3 Parts.” ThoughtCo, ThoughtCo, 10 Dec. 2019, www.thoughtco.com/know-the-kinds-of-nucleotides-4072796.

[2]Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic SignificanceBjarne Hove-Jensen, Kasper R. Andersen, Mogens Kilstrup, Jan Martinussen, Robert L. Switzer, Martin WillemoësMicrobiology and Molecular Biology Reviews Dec 2016, 81 (1) e00040-16; DOI: 10.1128/MMBR.00040-16.

[3] Voet, Donald; Voet, Judith; Pratt, Charlotte (2008). Fundamentals of biochemistry : life at the molecular level(3rd ed.). Hoboken, NJ: Wiley. ISBN9780470129302.

[4] Jewett, M. C., Miller, M. L., Chen, Y., & Swartz, J. R. (2009). Continued protein synthesis at low [ATP] and [GTP] enables cell adaptation during energy limitation. Journal of bacteriology191(3), 1083–1091. https://doi.org/10.1128/JB.00852-08.

[5] Sögüt, Sadik, et al. “The Activities of Serum Adenosine Deaminase and Xanthine Oxidase Enzymes in Behcet’s Disease.” Clinica Chimica Acta; International Journal of Clinical Chemistry, U.S. National Library of Medicine, Nov. 2002, www.ncbi.nlm.nih.gov/pubmed/12367777.

[6] Moffatt, B. A., & Ashihara, H. (2002). Purine and pyrimidine nucleotide synthesis and metabolism. The arabidopsis book1, e0018. https://doi.org/10.1199/tab.0018.

[7] Rabinowitz, J. D., Hsiao, J. J., Gryncel, K. R., Kantrowitz, E. R., Feng, X. J., Li, G., & Rabitz, H. (2008). Dissecting enzyme regulation by multiple allosteric effectors: nucleotide regulation of aspartate transcarbamoylase. Biochemistry47(21), 5881–5888. https://doi.org/10.1021/bi8000566.

[8] SAUER, F., PUGH, E. L., WAKIL, S. J., DELANEY, R., & HILL, R. L. (1964). 2-MERCAPTOETHYLAMINE AND BETA-ALANINE AS COMPONENTS OF ACYL CARRIER PROTEIN. Proceedings of the National Academy of Sciences of the United States of America52(6), 1360–1366. https://doi.org/10.1073/pnas.52.6.1360.

[9] van Gennip, A H, et al. “Beta-Aminoisobutyric Acid as a Marker of Thymine Catabolism in Malignancy.” Clinica Chimica Acta; International Journal of Clinical Chemistry, U.S. National Library of Medicine, 15 June 1987, www.ncbi.nlm.nih.gov/pubmed/3652458.