DNA Notebook

Let us be a resource and a window into the advances in personalized medicine driven by DNA testing.

What is a biological pathway?

Introduction

Biological pathways are often multifaceted and require some background knowledge in order to understand the principle mechanisms and functions. This series of short topics will give you a better idea of how your genes affects how well your body processes medication. This is the basis for how MatchMyMeds works!

What does the liver do?

The function of the liver is to metabolize, or break down, different substances in your body. These substances may be nutrients or toxins[1]. Nutrients are converted into useful molecules that your cells can use as an immediate energy source or store for future use. Toxins are broken down into smaller, harmless units and are removed from the body.

Both of these metabolic pathways would not be possible without enzymes. Enzymes are a type of protein that increase how fast molecules are rearranged. Without these proteins, any metabolic process would take much longer to complete. A faulty enzyme in the liver would result in a build-up of toxins or too little of an important energy source. A very important application of this liver function is the breakdown of drugs. If you would like more information, visit: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072577/

Looking closer at drug metabolism

When you take a medication, it is circulated through the bloodstream which allows it to reach different tissues and organs. Eventually it is carried to the liver, where enzymes break down the drug molecules into smaller pieces and removed from the body[2].

There are a few common enzymes that are responsible for drug metabolism. The main type of enzymes that metabolize drugs are cytochrome P-450. This enzyme breaks down many different medications, from cardiovascular medications, to antidepressants, or even painkillers. Different enzymes can break down drugs at a various rates. For more information, visit https://www.merckmanuals.com/en-ca/home/drugs/administration-and-kinetics-of-drugs/drug-metabolism

Genes & Metabolism

Every person’s reaction to a substance, whether it’s caffeine, aspirin, or insulin, varies drastically. One of the underlying reasons for this is variation in our DNA. As explained in a previous blog [link to Genetics 101 blog, “click for a quick genetics refresher”], humans share nearly identical DNA sequences with a 0.1% variation. Changes in single bases of the genome, SNPs [scroll over or link for definition/clarification], are a major category of this variation. SNPs found in genes [scroll over or link to ‘gene’ definition’] that codes for proteins causes changes in the structure and function of that protein.

How does this relate to drug metabolism [scroll over or link to metabolism definition]? Due to variations in your genetic makeup, liver enzymes may interact with, and metabolize, medications at different rates and efficacy levels. As a result, the variation of the enzyme that your body produces becomes very important. If it is able to metabolize a certain medication faster, it may be necessary to have a higher dosage of the drug. Inversely, a slower metabolizer results in build-up of the drug, making it important to appropriately lower the dosage.

This, in a nutshell, is pharmacogenetics. It is the study of how variations in the genome, that result in slightly different protein structures, are important to keep track of to ensure proper prescription of drugs. For more details and examples, visit: https://www.merckmanuals.com/en-ca/home/drugs/factors-affecting-response-to-drugs/genetic-makeup-and-response-to-drugs#v715903

[1] https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072577/

[2] https://sunrisehouse.com/cause-effect/path-drugs-take-body/

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