Let’s Talk About The Liver

By Elaine Novik and Aaron Goldman

The function of the liver is to filter out our blood and metabolize, or break down, different substances in our bodies. These substances may be chemical toxins found in the food we eat or the air we breathe; they may be metabolites created in our day-to-day biological processes; or they may be nutrients or medications that need to be metabolized. Nutrients are converted into useful molecules that your cells can use for example as an immediate energy source or stored for future use. Toxins (including medications) are broken down into smaller, harmless units and are removed from the body so as to avoid having too much which can lead to unwanted side effects.

These metabolic pathways would not be possible without enzymes. Enzymes are a type of protein that increase how fast molecules are modified. Without these proteins, metabolic processes would take much longer to complete, or may not take place at all. A faulty enzyme in the liver could potentially result in a build-up of toxic chemicals or too little of an important energy source.

Let’s take a closer look at drug metabolism.

When you take a medication, it circulates through your 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 can be removed from the body.

There are a few common enzymes that are responsible for drug metabolism. The main type of enzymes that metabolize drugs are from the cytochrome P-450 family of enzymes. These enzymes break down many different medications, from cardiovascular drugs like statins, to antidepressants and anti-anxiety meds, painkillers like ibuprofen and opioids, proton pump inhibitors like Nexium, and many others. Different enzymes can break down drugs at various rates, and we all carry genetic variations that impact how we metabolize these drugs, and can inform a more personalized approach to prescribing.

Genes & Metabolism.

Every person’s reaction to a substance, whether it’s caffeine, codeine, or carbohydrates, can vary drastically. One of the underlying reasons for this, and arguably one of the most important reasons, is variation within our DNA. Genetic variations within our genes that encode the cytochrome-P450 family of enzymes are very common in the population. In fact, about 80% of people carry genetic variants that would influence how they metabolize drugs. These genetic variants in genes that encode drug metabolizing enzymes cause changes in the structure, function, and or expression levels of that enzyme and can result in a person metabolizing a drug too slowly or too quickly.

How does this change in drug metabolism impact drug safety and/or efficacy? If an enzyme metabolizes a certain medication too quickly, it may be cleared out of your system so fast that it never accumulates to therapeutic levels, and thus it may be necessary to increase dosage of the drug in order for it to be effective. Conversely, if a genetic variation results in an enzyme that functions too slowly, the drug may not be cleared from your bloodstream quickly enough and can result in the build-up of the drug to toxic levels, and can result in unwanted side effects. In this case, it may be important to use a lower dosage.

This, in a nutshell, is pharmacogenetics. It is the study of how variations in our genes can influence drug metabolism by impacting the activity of drug-metabolizing enzymes. Understanding what variants you carry can be important in ensuring a safer and more effective way of prescribing medications.

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