Function of Cytochrome P450

Introduction

Humans are continuously exposed to a wide variety of environmental chemicals, drugs, food additives, and pollutants that could eventually impair cellular metabolism with detrimental effects on health. Defense systems that contain as their centerpiece the unique hemeprotein cytochrome P450 (CYP) have evolved to protect organisms against toxic compounds. However, CYP-mediated biotransformation may result in metabolic activation of environmental chemicals to reactive carcinogenic products, a process often referred to as lethal synthesis.

CYPs continue to receive the attention of biochemists and pharmacologists because of their pivotal role in the detoxification of xenobiotics as well as diverse endogenous compounds such as steroids, bile acids, unsaturated fats, prostaglandins, and leukotrienes. CYPs play a predominant role in the metabolism of carcinogens and drugs that mitigate cancer growth. Thus, inhibitors of CYP enzymes may potentially serve as anticancer agents.

Occurrence and Functions

CYPs constitute a superfamily of hemeproteins ubiquitously found in animals, plants, fungi, and bacteria. In mammals, CYP enzymes are present in all tissues with highest concentrations in the liver and small intestine. These are membrane-bound proteins that abound in the microsomal fraction of the liver, and have a crucial role in bile acid biosynthesis, and metabolism of foreign compounds such as drugs, environmental pollutants, and carcinogens. CYPs are also present in the mitochondrial inner membranes of steroidogenic tissues such as adrenal cortex, testis, ovary, breast, and placenta, and are involved in the synthesis and degradation of endogenous steroid hormones. In addition, CYP enzymes play a major role in vitamin metabolism, oxidation of unsaturated fatty acids, and cholesterol biosynthesis. Specific functions have been documented for CYPs in the brain including regulation of endogenous GABAA receptor agonists, maintenance of brain cholesterol homeostasis and elimination of retinoids. Thus CYPs play a central role in cellular metabolism and maintain cellular homeostasis.

Figure 1. The P450 catalytic cycle.

Identification of moonlighting CYPs has added a new dimension to the complexity and the repertoire of functions catalysed by this large superfamily. CYP170A1, the first moonlighting CYP to be discovered, was found to function both as a monooxygenase and terpene synthase. This bifunctional protein isolated from the Gram-positive bacterium Streptomyces, was shown to switch between two distinct active sites in its structure in order to catalyse two unrelated biochemical activities. CYP17 (17α-hydroxylase/17–20 lyase), a microsomal enzyme that plays a role in steroid hormone biosynthesis, functions as a 17α-hydroxylase during the biosynthesis of cortisol in the adrenal cortex, whereas in the gonads it is involved in the biosynthesis of androgens as a 17–20 lyase. CYP7B1 performs a broad spectrum of functions in diverse tissues. This enzyme functions as a steroid 7α-hydroxylase in the brain using pregnenolone and dehydroepiandrosterone as substrates. In the liver, CYP7B1 catalyzes bile acid synthesis with both 25- and 27-hydroxycholesterol as substrates. CYP7B1 is involved in the inactivation of the 19-carbon steroid, 5α-androstane-3β, 17β-diol that binds to the estrogen receptor in the prostate gland. In addition, the enzyme also catalyzes the conversion of dehydroepiandrosterone to 7α-hydroxydehydroepiandrosterone that accumulates in synovial fluid in patients with rheumatoid arthritis.

Reference:

Palrasu M, Siddavaram N. Cytochrome P450 Structure, Function and Clinical Significance: A Review. Current Drug Targets, 2018, 19(1).

Related Products at Creative Enzymes:

Cytochrome P450 Reductase

Cytochrome P450 Monooxygenase

20 Comments

  1. Hi there, You’ve performed a great job. I will certainly digg it and individually suggest to my friends. I’m sure they’ll be benefited from this web site.|

  2. I discovered your blog site on google and check a few of your early posts. Continue to keep up the very good operate. I just additional up your RSS feed to my MSN News Reader. Seeking forward to reading more from you later on!…

  3. We’re a group of volunteers and opening a new scheme in our community.

    Your website provided us with valuable info to work on. You’ve done
    a formidable job and our entire community will be thankful
    to you.

  4. Hey! This is my first visit to your blog! We are a collection of volunteers and starting
    a new project in a community in the same niche. Your blog provided us valuable
    information to work on. You have done a extraordinary job!

  5. Howdy! I realize this is sort of off-topic but I needed to ask.
    Does running a well-established website like yours require a large amount of work?
    I am brand new to operating a blog however I do write in my diary
    every day. I’d like to start a blog so I can share my own experience and thoughts online.

    Please let me know if you have any kind of suggestions or
    tips for brand new aspiring bloggers. Appreciate
    it!

  6. I blog frequently and I genuinely thank you for your information. Your article has really
    peaked my interest. I will bookmark your blog and keep checking for
    new information about once a week. I opted in for your RSS feed
    too.

  7. Hey There. I found your blog using msn. This is an extremely well written article.

    I will be sure to bookmark it and return to read more of
    your useful info. Thanks for the post. I will definitely return.

  8. I am really enjoying the theme/design of your site.
    Do you ever run into any web browser compatibility issues?

    A couple of my blog audience have complained about my website not working correctly in Explorer but looks great in Opera.
    Do you have any recommendations to help fix this issue?

  9. Heya! I just wanted to ask if you ever have any issues
    with hackers? My last blog (wordpress) was hacked and I ended up losing many months
    of hard work due to no backup. Do you have any methods
    to protect against hackers?

  10. Whats up this is kinda of off topic but I was wondering if blogs use WYSIWYG editors
    or if you have to manually code with HTML. I’m starting a blog soon but have no coding know-how so I wanted to get advice from someone with experience.
    Any help would be greatly appreciated!

  11. You really make it appear really easy along with
    your presentation but I in finding this matter to be actually one
    thing that I feel I’d never understand. It sort of feels too complex and
    extremely large for me. I am having a look ahead to your next put up, I’ll try to get the hang of it!

  12. Thank you, I’ve just been searching for info about this subject for ages and yours is the best I’ve came upon so
    far. But, what in regards to the bottom line? Are you sure
    about the source?

  13. hello!,I like your writing so a lot! proportion we keep up a correspondence more approximately your post on AOL?
    I require a specialist on this area to unravel my
    problem. May be that’s you! Looking ahead to see you.

Leave a Reply

Your email address will not be published.


*