Cytochrome P-450

A super family of proteins or enzymes, cytochrome P450 (CYP) has a pivotal role in metabolism. These enzymes also work to inactivate alien substances as well as toxins in our body, thereby protecting us from various ailments. All the proteins belonging to this family are extremely specialized and have distinctive and dedicated pathways within the cells.

Every day, we, humans, are exposed to various pollutants, chemicals, food additives, and drugs present in our environment that may have several adverse effects on our health. When we are exposed to these harmful substances for a long period of time, they may in due course damage the metabolism in the cells, thereby affecting our health adversely. However, the body's defence systems, which contain the only one of its kind hemeprotein cytochrome P450 (CYP) as their centerpiece developed to protect the organisms from these toxic chemicals. Nevertheless, biotransformation due to CYP mediation may often activate the harmful chemicals present in the environment to transform into reactive cancer causing substances - a process is known as lethal synthesis.

Cytochrome P450 works to catabolize or break down complex substances or compounds into simpler substances while producing energy. This energy is helpful in getting the body rid of harmful chemicals, drugs and pesticides, which are often intentionally or inadvertently catabolized into carcinogenic compounds. These proteins or enzymes aid in catalyzing the synthesis of cholesterol, steroid hormone, arachidonate metabolites and bile acids and, at the same time, assist in breaking down endogenous compound into steroids and fatty acids.

Cytochrome P450 (CYP) also catalyzes reactions with aliphatic as well as aromatic hydroxylation, O-, N-, S-dealkylations, and heteroatoms' oxidation. At times, oxidative metabolism also results in dangerous toxins. Some external energy is required for the catabolize reactions and this energy is generated by NADH (Nicotinamide adenine dinucleotide) as well as secondary proteins that are called puidaredoxine reductase P450cam and putidaredoxine for transferring the electrons to cytochrome P450.

Biochemists and pharmacologists are continuously studying CYPs or cytochromes P450 since they have a key role in detoxifying xenobiotics and various other diverse endogenous compounds like bile acids, steroids, prostaglandins, unsaturated fats and leukotrienes. These proteins have a leading role in the metabolism of drugs and carcinogens that promote cancerous growth. Hence, substances that inhibit cytochrome P450 (CYP) have the potential to work as agents that help to prevent growth and spread of cancer.

Cytochrome P450 enzyme

Proteins are necessary for creating cytochrome P450 (CYP) enzyme. We all know that cytochrome P450 is important for us, but how vital is it. As mentioned earlier, cytochrome P450 is actually a family comprising 50 diverse enzymes that are present in all the cells of our body. The highest concentration of cytochrome P450 is found in the liver cells. This is because they are essential for detoxifying the liver. These enzymes have various actions and the important ones are described briefly below.

Cytochrome P450 (CYP) enzymes function inside the liver during the detoxification process. These enzymes also help to detoxify xenobiotic sources of chemicals, carcinogens, alcohols and other toxic substances and convert these harmful substances into simpler substances such as water and oxygen. They also help the endogenous sources of waste materials like bilirubin and also in vitamin D synthesis.

These enzymes also play a vital role in synthesis of hormones. Cytochrome P450 (CY) is effective in converting cholesterol into pregnenelone, which is subsequently converted into various hormones such as testosterone, estrogen, DHEA and cortisol. These enzymes also help in synthesizing bile as well as bile acids. These are essential to absorb fat soluble vitamins. In fact, bile also encloses several toxic substances that are conjugated within the liver. These toxins are subsequently deposited in the bowels and finally eliminated from the body as stools.

Some people may suffer from deficiency of this vital enzyme family. People who have CYP deficiency are those who do not eat enough dietary protein and also people having elevated levels of toxicity in their body. This enzyme system is found in the epithelial lining of the gastro-intestinal (GI) tract and people who do not have enough of these enzymes in their body often suffer from colon cancer. People enduring pathological problems also have a deficiency of cytochrome P450.

It is surprising to note that aside from the environmental toxins, over 900 pharmaceutical drugs are responsible for causing liver toxicity. Apart from this, there are many drugs that work to inhibit the action of cytochrome P450 (CYP) enzymes and they may damage the liver further. Shockingly, it is suspected that about 90% cancers are caused owing to the carcinogens present in the environment.

When there is too much xenobiotic toxicity it may result in excessive use of cytochrome P450 enzymes. This, in turn, may lead to presence of excessive detrimental free radicals in the body.

Occurrence and functions of cytochrome P450

Cytochrome P450 (CYP) comprises a family of heme enzymes or proteins that are universally present in animals, plants, bacteria and fungi. In the instance of mammals, these proteins are found in all the tissues, with the maximum concentration in their liver and small intestine. These proteins are membrane-bound that are found in abundance in the liver's microsomal fraction. They play a vital role in the biosynthesis of bile acid. In addition, they are involved in the metabolism of alien harmful substances in the body such as drugs, carcinogens and environmental pollutants. Apart from this, cytochrome P450 enzymes are found in the steroidogenic tissues' mitochondrial inner membranes. The steroidogenic tissues include breast, testis, ovary, cortex and placenta. These enzymes also have an important part in metabolism of vitamins as well as break down of endogenous steroid hormones. Scientists have documented specific functions of cytochrome P450 (CYP) in the brain, where these enzymes work to regulate endogenous GABAA receptor (GABAA R) antagonists, eliminate retinoids and maintain brain cholesterol homeostasis. In this way, this family of super enzymes plays a pivotal role in metabolism within the cells and also preserves cellular homeostasis.

Isolated from gram-positive bacterium Streptomyces, CYP170A1 is a bi-functional protein that has demonstrated it has the ability to switch between two dissimilar active sites within its structure with the purpose of catalyzing two separate biochemical activities. In fact, CYP17 (also known as 17 α-hydroxylase/17-20 lyase) is basically a microsomal enzyme which has an important role in biosynthesis of steroid hormone and, at the same time, it functions in the form of a 17α-hydroxylase at the time of cortisol biosynthesis inside the adrenal cortex. On the other hand, it has a role in androgen biosynthesis in the form of as 17-20 lyase in the gonads.

CYP7B1, this enzyme has a wide range of functions in various different tissues. In the brain, this enzyme serves as a steroid 7α-hydroxylase making use of dehydroepiandrosterone and pregnenolone as substrates. Within the liver, this enzyme works to catalyze the synthesis of bile acid with 25- and 27-hydroxycholesterol as substrates. In addition, CYP7B1 also plays an important role in activating the 19-carbon steroid known as 5α-androstane-3β, 17β-diol, which attaches to the receptor of estrogen inside the prostate gland. Apart from this, CYP7B1 helps to catalyze dehydroepiandrosterone conversion into 7α-hydroxydehydroepiandrosterone. In people suffering from rheumatoid arthritis, 7α-hydroxydehydroepiandrosterone accumulates in the synovial fluid.


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