Is this one enzyme or two? two polypeptides of a single enzyme? is this a family of CYPs?
Any reference to explain this would be highly appreciated?
Hello Gunjan,
These are three cytochromes P450 of the CYP2B subfamily "expressed" by rats, at least there are three different cyp2b-encoding genes in rat genome.
Rats express three CYP2Bs: Cyp2b1, Cyp2b2 and Cyp2b3. Rabbits express one CYP2B: namely CYP2B4. Humans express one CYP2B, namely CYP2B6 and Dogs express also only one CYP2B enzyme, namely CYP2B11.
So in rats, you have three CYP2B enzymes. One is CYP2B1 whose gene is harbored by rat chromosome VII (from 99,140 kb to 99,185 kb). This is the most studied rat CYP2B enzyme. CYP2B2 and CYP2B3 are two different polypeptides, encoded by two distinct genes which are found in tandem association on rat chromosome I (cyp2b2 from 83,100 kp up to 83,120 kb and cyp2b3 from 83,160 kb up to 83,240 kb).
Therefore, these three rat CYP2B enzymes being encoded by three distinct genes are three different polypeptides and are thus three different enzymes. They are considered as three members of the same P450 SUBFAMILY (the CYP2B subfamily) which is one of the several subfamilies included in the CYP2 family.
For your information, rat CYP2B1 is 97 % identical in amino acid sequence to rat CYP2B2 (very very similar !!!!) and 77% identical to rat CYP2B3. ANd rat CYP2B2 is 76% identical to rat CYP2B3. I joined a pdf file showing the multiple alignment of the three rat CYP2B proteins.
I hope to have helped you to understand this system by answering your questions!
Best regards,
Pr Philippe Urban
Dear Gunjan Pandey,
With all usefulness of information provided by Dr. Philippe Urbun for cytochromes P450 of the CYP2B subfamily expressed by rats, please keep in mind that an expression of rat CYP2Bs by itself has no correlation with the exact monooxygenase activity CYP2B1/2 catalyzes, because for rat CYP2B1/2 it was shown that not its expression and the content but non-genetic factors play the crucial role. For example, please find just published paper of Yu-Ting Tai et al. (2015)
BioMed Research International
Volume 2015 (2015), Article ID 658928, 11 pages
http://dx.doi.org/10.1155/2015/658928
Ring-Oxidative Biotransformation and Drug Interactions of Propofol in the Livers of Rats
Administration of phenobarbital to male Wistar rats significantly increased levels of hepatic cytochrome P450 (CYP) 2B1/2 and microsomal pentoxyresorufin O-dealkylase (PROD) activity. Analyses by high-performance liquid chromatography and liquid chromatography mass spectroscopy revealed that propofol was metabolized by phenobarbital-treated rat liver microsomes into 4-hydroxypropofol. In comparison, PROD activity and 4-hydroxy-propofol production from propofol metabolism were suppressed by orphenodrine, an inhibitor of CYP2B1/2, and a polyclonal antibody against rat CYP2B1/2 protein. Furthermore, exposure of rats to propofol did not affect the basal or phenobarbital-enhanced levels of hepatic CYP2B1/2 protein. Meanwhile, propofol decreased the dealkylation of pentoxyresorufin by phenobarbital-treated rat liver microsomes in a concentration-dependent manner. Taken together, this study shows that rat hepatic CYP2B1/2 plays a critical role in the ring-oxidative metabolism of propofol into 4-hydroxypropofol, and this anesthetic agent can inhibit CYP2B1/2 activity without affecting protein synthesis.
Best wishes,
Ilya
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