# Structural Biochemistry/Drug metabolism enzymes
### Introduction

Drug metabolizing enzymes are enzymes that are used to carry out reactions during drug metabolism; they are enzymes that metabolize xenobiotics (Tukey 71). Xenobiotics are defined in biochemistry as foreign chemicals or substances to a certain species. Thus, drugs can be grouped in this category of xenobiotics as well because drugs are foreign substances that enter the body. Xenobiotics are not limited to just drugs; there are many other chemicals that are considered xenobiotics.
There is generally two stages in which drug metabolism is facilitated and they may occur in most of the body. However, it is most likely that they are carried out in the liver and small intestines because the small intestines is where chemicals are absorbed and sent out to the liver (Tukey 74).

### Function

How does it work? First, drugs must be transformed into a different form that the cells can access because they are required to move down a gradient and most drugs are hydrophobic (Gonzalez 71). This means that the chemicals that enter the cell must be hydrophilic or changed into hydrophilic chemicals in order for the cells to eliminate the toxins more easily. The enzyme that is allowed to make the change from a hydrophobic substance to a hydrophilic chemical are drug metabolizing enzymes. Then the drug is passed through the gastrointestinal tract where metabolism is first started; if the drug is not broken down all the way, it is then passed to the liver where more metabolism takes place until the chemical is fully broken down (Tukey 74).
For example, metabolism of phenytoin by the enzyme CYP450 and UGT will make the drug very hydrophilic and thus it will be able to be broken down by the body and taken in by the small intestines into the body (Tukey 72). Also the molecular weight of the compound increases as well which increases the elimination of the drug through urine or the bile (Tukey 72).
Drug metabolizing enzymes not only breaks down chemicals but it may also cause cancer because it may change the toxic accumulation of chemicals into carcinogens which are cancer causing agents (Tukey 72). It usually happens when the converted chemical decides to react with other compounds in the cell like DNA or RNA which may result in mutations and lead to cancer.

## Drug Metabolism Role in Efficient Drugs

How does metabolism connect to the making of drugs for patients?
The role of metabolism is to rid toxic chemicals from the body in order to keep it from entering a toxic state; thus, when drugs are consumed, metabolism will do its job to eliminate the drugs. Therefore, if a drug is eliminated at a rapid rate, this means that the drug is not very efficient (Gonzales 88). Vice versa, if the drug is not metabolized fast enough, then the body will enter a poisonous state. This concludes that metabolism will reduce the efficiency of a drug if it's job is to break down the drug. So, using this information, scientists are able to link metabolism with the efficiency of the drug and so they are able to create drugs that fit the needs of patients according to the studies of the rates of metabolism of different drugs.
However, there is a problem because environmental factors may also contribute the changes in the rate of metabolism. For example, grapefruit juice should not be used to take medication because it has chemicals in it that stop the CYP3A4 enzyme which increases the amount of that drug available (Gonzalez 78). This might sound good that it increases the availability of the drug but this is not the case; the increase of the drug will result in toxicity but will also effect the efficiency of the drug as well so it has its pros and cons. Therefore, it is very difficult for scientists to control the rate of metabolism for a group of individuals with so many different factors changing the rate of metabolism. But with this knowledge, scientists may then follow through their research to hopefully find something to work with.

### Significance

Drug metabolizing enzymes helps eliminate certain chemicals that are harmful to the body through a series of reactions and processes. Therefore, without drug metabolizing enzymes then metabolism will not occur. As a result, harmful chemicals and other substances that are not able to metabolize, will accumulate in the species and will cause the individual to be in a poisonous state. All in all, it is important for an individual to have these enzymes to be able to eliminate xenobiotics (chemicals not known to the individual)to avoid toxicity.

### Overview

There are enzymes that are needed to facilitate drug metabolism. Two recognized enzymes would be CYP3A4 and CYP450. CYP3A4 is a drug-metabolizing enzyme that is located in the intestines. It increases or alters blood vessels of certain medications in people. CYP450 is a cytochrome enzyme that processes essential molecules such as hormones and vitamins. They also help break down many prescribed medicines and natural substances. Both enzymes aid the process of drug metabolism in our bodies.
Scientists have discovered that many different codes for CYP 450 genes can be found in the human genetic code. This leads to CYP 450 proteins having a wide range of activity. An example is that some CYP enzymes can metabolize carcinogens, which activates the chemicals and has a tendency to cause cancer. Studies have shown that CYP 450 can be blocked by natural components that can be found in certain food. These include oranges, horseradish, green tea, and mustard.

#### Reference

Davis, Alison. (2006). Medicines By Design. National Institutes of Health, 8.
Gonzalez, Frank J.; Tukey, Robert H. "Drug Metabolism: How Humans Cope with Exposure to Xenobiotics." Goodman and Gilman's the Pharmacological Basis of Therapeutics. By Frank J. Gonzalez. New York, NY: McGraw-Hill, n.d. 71-91. 21 Nov. 2012.