Cytochrome P450 || P450
What is Cytochrome P450 ?
Cytochrome P450 is Enzyme having large superfamily of monooxygenases that is helps to metabolized various compound in human and animal and plant.
Function is catabolized the compound which produce the energy, helps to remove the drug , chemical, pesticide which is taken knowingly or unknowingly, catabolized carcinogens compound , Catalyze synthesis of steroid hormone, cholesterol , bile acids ,arachidonate metabolites and also help the degaradation of endogenous compound as fatty acid and steroids.
The reaction catalyzed in cytochrome P450s with aliphatic and aromatic hydroxylation ,N- ,O-, S-dealkylations and also oxidationof heteroatoms. Some time oxidative metabolism produce the harmful toxin. For the reaction required some external energy which is produce by NADH(Nicotinamide adenine dinucleotide) and auxiliary proteins known as putidaredoxine and puidaredoxine reductase P450cam to transfer the electronsto P450.
How many cytochrome P450 are presents ?
There are 1000 P450 gene are present or identified. All the gene are make the superfamily .
There are 4 Class divided the superfamily.
Mitochondria of eukaryotes are member of this class I. In this class two electron transfer protein are found such as FAD(flavin adenine dinucleotide reductase and an Iron sulfur Protein.
In this group only one electron transfer proton required. Reductase both the contains FAD and FMN(Flavin mononucleotide).This class of enzymes are metabolized Drug ,toxicchemical or steroidogenic .it found in the endoplasmic reticulum of eukaryotes and all the mammalian cell.
This class of enzyme donot required any electron transfer group and it act on peroxy fatty acid .some example are thromboxane synthase and allene oxide synthase.
This class is also don’t required electron transfer partners, it insist the directly bind and transfer the electron form pyridine nucleotide to heme iron.some example fungi fusarium oxysporum P450nor, nitric oxide reductase
First active site of cytochrome P450 contain a heme iron which is located in the center Fe3+ so it is stable state according to the valency of ferric ion. Now NADPH is give the electron then reduction takes place form Fe3+ to Fe2+ then it is active state and it easily bind with drug to metabolize . normally cytochrome P450 enzyme have many hydroxyl group are present which is help to drug excreated through the Kidney.
According to study 75% drug are metabolize by this procress.
RH +O2+NADPH +H+ __________→ROH+ H2O +NADP+
Microsomal P450 systems:
In which electrons are transfer form NADPH by the help of cytochrome P450 reductase .Cytochrome b5 is also reducing power to this system followed by cytochrome b5 reductase.
Mitrochondrial P450 systems
In this procress adrenodoxin reductase and adrenodoxin are help to transfer the electron form NADPH to P450.
Bacterial P450 systems
In this procress ferredoxin reductase and ferredoxin are help to transfer the electron .
In this procress what is electron required comes form cytochrome b5
Most common reaction catalyzed cytochrome P450 is monooxygenase reaction .
Cytochrome family in the human
In the human being total 57 genes are present and 43 subfamily are present, 49 pseudogenes are present .
Below I discuss some important family and its function
It mainly metabolized drug and steroid like estrogen is CYP1A1,CYP1A2,CYP1B1
Drug and steroid metabolism and this family having 13 subfamily and 16 genes and 16 pseudogenes. CYP2A6, CYP2A7, CYP2A13,CYP2B6, CYP2C8,CYP2C9,CYP2C18,CYP2C19,CYP2E1,CYP2F1,CYP2J2,CYP2R1,CYP2S1,CYPP2U1,CYP2W1.
Drug and steroid also testosterone are metabolized by this family of enzyme having 1 subfamilly ,4 genes and 2 psedogenes .CYP3A4,CYP3A5,CYP3A7,CYP343
Arachidonic acid and fatty acid metabolism are conatin 6 subfamilly ,12 gene,10 psedogenes.CYP4A11,AYP4A22,CYP4B1,CYP4F2,CYP4F2,CYP4F3,CYP4F8,CYP4F11,CYP4F12,CYP4F22,CYP4V2,CYP4X1,CYP4Z1
This family enzyme help to metabolized thromboxane A2 synthse having 1 subfamilly and 1gene CYP5A1.
This family of enzyme help to steroid biosynthesis having 2 subfamily and 3 gene CYP11A1,CYP11B1,CYP11B2
This family of enzyme help to steroid biosynthesis as well as 17-alpha hydroxylase having 1 subfamily ,1 gene.CYP17A1
This family of enzyme help vitamin degaradation having 1 subfamily and 1 gene .CYP24A1
This family enzyme helps to cholesterol biosynthesis having 1subfamily, 1gene,3 pseudogenes.CYP51A1 .