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What is CYTOCHROME P450

                CYTOCHROME P450

INTRODUCTION:

Cytochrome P450,also known as(CYPs)are a family of enzymes which contain heme as a cofactor that function as monooxygenase.There are five kingdoms in which living organisms are divided according to their characteristics.These are,

  • Animal
  • Plantae
  • Fungi
  • Monera
  • Protists

Cytochrome P450 has been identified in every kingdom.in mammals these enzymes oxidize steroids,fatty acids and convert it into fats. Cytochrome P450 synthesise various body hormones.in plants,these enzymes play an important role for the biosynthesis of defensive compounds,fatty acids and hormones.More than 50,000 distinct types of cytochrome p450  proteins are known.They are present in every organism except some ,For Example:ESCHERECHIA COLI.

STRUCTURE:

Cytochrome P450 are made up of protein and have heme as the central atom.as we have studied that CYTOCHROME P450 are enzymes.they have an active site which breaks the substrate into products.Active site is the part of the enzyme where substrate attach and the catalytic activity proceeds.in this case CYTOCHROME P450 have an active site on which a protein attaches with the help of CYSTEINE THIOLATE LIGAND.they form a complex pattern.

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                                             As we discussed earlier that there are over 50,000 types of CYTOCHROMEP450 and because the cytochromep450 do many kinds of reactions,each is differ from the other one.

CYTOCHROME P450 iN HUMANS:

                                                              In humans CYTOCHROME P450 have primarily a single membrane-associated protein.In humans CYTOCHROME P450 may be present in the inner membrane of MITOCHONDRIA or ENDOPLASMIC RETICULUM.as we know that mitochondria is an important organelle in human cells as it is also called as the powerhouse of the cell. Mitochondria is an energy producing organelle. Mitochondria extends from cell membrane to the nuclear membrane.it may be rough or smooth.rough endoplasmic reticulum have ribosomes which are factory of proteins and smooth part of the endoplasmic reticulum works as it transfer waves produce energy etc.thousand of chemicals like ENDOGENOUS and EXOGENOUS are metabolized in the body by CYTOCHROME P450.

     Some cytochromes have ability to transfer only 1 substrate at a time and some may convert multiple substrates in products in the human body.

IMPORTANCE:

  •   CYTOCHROME P450 have a central importance in medicine.
  •    They may metabolise multiple substrates into product at a time.
  •    They make most of the tissues of the body.
  •    They play an important role in breaking and synthesis of some important chemicals.
  •    Hormone synthesis and breakdown.
  •    Cholesterol synthesis and vitamin-d metabolism.
  •    Cytochrome P450 play a principal role in liver by breaking drug products and metabolizing toxic chemicals.

75% of total drug metabolism in the body is done by CYTOCHROME P450.

CYTOCHROME P450 in animals:

                The classes or types of CYTOCHROME P450 investigated in non-humans have a different gene-regulation and different enzymatic functions.Many animals have as many or more cytochrome p450 genes than humans do.There are observed differences of CYTOCHROME P450 in related animals.In both species some of the drugs are metabolised via different enzyme which result in different metabolism activities.products are unchanged in one specie and drugs are metabolized in other specie.But effects in humans and animals would not be the same.

Many animals have more CytochromeP450 genes as compared in humans.In animals most of cytochrome p450 enzymes show monooxygenase activity.many genes in cytochromes have been studied that gives clues about their functionality.they are also involved in the metabolism of toxic compounds.

Cytochrome p450 are precisely examined more on mice , rats , dogs and less on zebrafish.it has been discovered that avian species also contain cytochrome p450.in some situations they are turned out as an effective way of treatment from cancer.

According to a survey,we found that there are almost 2,500,000 species of organism are present and 53.1% of them are insects and 19.9% are animals.CYTOCHROME P450 are found in insects.  

Cytochrome P450 in MICROBES:

                                                     In microbes CYTOCHROME P450 is present also in the form of enzymes which are involved in diverse metabolic activities.They are also known as soluble enzymes.As we know bacteria is also a microbe,for example E.COLI.Some bacteria have numerous CYTOCHROMES P450 and every type is different in different microbes or bacteria.Those which are identified in microbes may be either involved in biotransformation or may be a part of specialised metabolic biosynthetic pathways.As we have discussed earlier that microbial cytochrome p450 enzyme is soluble so they are regarded as easier to work with than the predominantly membrane bound eukaryotic cytochrome p450.They contribute to the survival of bacteria in the natural environment.

Cytochrome P450 in FUNGI:

                                                In fungi CYTOCHROME P450 works as an inhibition from fungal drugs.the commonly used azole belonging to class antifungal drugs works by inhibition of the fungal cytochrome P450.cytochrome P450 interrupts the formation of fungal drug by stopping the conversion of lanosterol to ergosterol.this is how the class antifungal works.human cytochrome p450 have a different sensitivity.fungi like CANDIDA and some species of ASPERGILLUS cause diseases in human.they are pathogens of humans and also of plants.

Cytochrome P450 in PLANTS:

                                          CYTOCHROME P450 are also present in plants but in plants they are used to target biomolecules and are involved in  a vast range of biosynthetic reactions.They are also involved in the reactions of conjugation of fatty acids. IN plants cytochrome P450 are involved in a variety of defensive compounds. Cytochrome P450 makes only 1% of plant gene. Diversity of cytochrome p450 gene in plants depends upon the multitude of bioactive compounds.

Role Of CYTOCHROME P450 in respiratory chain:

                                In the KREBS cycle NADH AND H+ are produced from NAD+. NADH then transfers the hydrogen atom to the respiratory chain also called Electron Transport Chain electrons are transported in a series of oxidation reduction steps to react, ultimately, with molecular oxygen.The oxidation reduction substances which take part in respiratory chain are:

  • A coenzyme called coenzyme-Q.
  • A series of cytochrome enzymes(b,a a,a3)
  • Molecular oxygen o2.

Cytochromes are electron transport intermediates containing haem of related  prosthetic groups,that undergo valency changes of IRON atom.HAem is the same iron containing group that is oxygen carrying pigment haemoglobin. 

NADH is oxidised by coenzyme Q. This oxidation yields enough free energy to permit the synthesis of a molecule of ATP from ADP and inorganic phosphate.coenzyme Q is in turn oxidised by cytochrome -c.THis step also yields enough energy in the form of ATP.

CYTOCHROME P450 in biotechnology:.

            The remarkable reactivity of cytochromep450 and substrate promiscuity had long attracted the attention of chemists.scientist had made progress two realize the potential of using cytochrome P450 towards difficult oxidations have included:

  1. Inexpensive peroxide containing molecules were used to eliminate the need of natural cofactors.
  2. Exploring the compatibility of cytochrome P450 with organic solvents.

Drugs:

Certain drugs may be the inhibitors or inducer to Cytochromep450.

Inducers of cytochrome p450:

  • Carbamazepine 
  • Rifampin
  • Phenytoin
  • Alcohol
  • Phenobarbital
  • Griseofulvin
  • Sulfonylureas

It means that all these compounds and chemicals are the inducers of cytochrome P450 enzyme.

Inhibitors of cytochrome p450:

  • Valproate
  • Ketoconazole
  • Isoniazid
  • Sulfonamides
  • Chloramphenicol
  • Amiodarone
  • Erythromycin
  • Quidine
  • Grapefruit juice

Subtypes of Cytochrome P450:

  1. CYP-1A2
  2. CYP-2E1
  3. CYP-2C9
  4. CYP-3A4

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