1: The substrate binds to the active site of the enzyme, in close proximity to the

heme group, on the side opposite to the peptide chain. The bound substrate
induces a change in the conformation of the active site, displacing a water molecule
from the distal axial coordination position of the heme iron[1] changing the state of
the heme iron. This gives rise to a change in the spectral properties of the enzyme,
with an increase in absorbance at 420~nm. Inhibitors and certain substrates that
bind directly to the heme iron give rise to the type~II difference spectrum. If no
reducing equivalents are available, this complex remains stable

http://en.wikipedia.org/wiki/File:P450cycle.svg

…………
 The cytochrome P450 superfamily (CYP) is a diverse group of enzymes. The function
of most CYP enzymes is to catalyze the oxidation.

CYP proteins containing a heme cofactor and, therefore, are hemoproteins. Often,
they form part of multi-component electron transfer chains, called P450-containing
systems which absorb light at wavelengths near 450 nm, identifiable as a
characteristic Soret peak.

http://en.wikipedia.org/wiki/Cytochrome_P450#cite_note-isbn0-470-01672-8-0

/////////////////

Role of cytochrome P450 enzymes in the bioactivation of

polyunsaturated fatty acids
Anne Konkela, and Wolf-Hagen Schunck

Abstract
Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA), such as epoxyeicosatrienoic acids and 20-
hydroxyeicosatetraenoic acid, serve as second messengers of various hormones and growth factors and play pivotal
roles in the regulation of vascular, renal and cardiac function. As discussed in the present review, virtually all of the
major AA metabolizing CYP isoforms accept a variety of other polyunsaturated fatty acids (PUFA), including linoleic,
eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), as efficient alternative substrates.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B73DJ-513369X-
1&_user=10&_coverDate=09/23/2010&_rdoc=1&_fmt=high&_orig=search&_origin
=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVer
sion=0&_userid=10&md5=f3b23bb581542b5a686bad7d037e28a9&searchtype=a
-----------------------

Arachidonic acid is a polyunsaturated fatty acid that is present in the phospholipids

(especially phosphatidylethanolamine,phosphatidylcholine and
phosphatidylinositides) of membranes of the body's cells, and is abundant in the
brain and muscles.

In addition to being involved in cellular signaling as a lipid second messenger

involved in the regulation of signaling enzymes, such as PLC-γ,PLC-δ and PKC-α, -β
and -γ isoforms, arachidonic acid is a key inflammatory intermediate.

http://en.wikipedia.org/wiki/Arachidonic_acid

Baynes, John W.; Marek H. Dominiczak (2005).Medical Biochemistry 2nd. Edition. Elsevier Mosby.
p. 555. ISBN 0723433410.

• Azole antifungals (e.g. the imidazoles: miconazole, clotrimazole, bifonazole,

imazalil, ketoconazole, and the triazoles: diniconazole, triadimenol,
propiconazole, fluconazole and itraconazole) inhibit in fungal cells the 14
alpha-demethylation of lanosterol or 24-methylenedihydrolanosterol. The
consequent inhibition of ergosterol synthesis originates from binding of the
unsubstituted nitrogen (N-3 or N-4) of their imidazole or triazole moiety to the
heme iron and from binding of their N-1 substituent to the apoprotein of a
cytochrome P-450 (P-450(14)DM) of the endoplasmic reticulum

Biochemical approaches to selective antifungal activity. Focus on azole

antifungals.
Vanden Bossche H, Marichal P, Gorrens J, Coene MC, Willemsens G, Bellens D, Roels I, Moereels H, Janssen PA.

• Azole antifungals (such as itraconazole) cause inhibition of ergosterol

synthesis which originates from binding of the unsubstituted nitrogen of their
imidazole or triazole moiety to the heme iron and from binding of their N-1
substituent to the apoprotein of a cytochrome P-450 of the endoplasmic
reticulum
http://www.fasebj.org/content/6/2/745.abstract

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B73DJ-513369X-
1&_user=10&_coverDate=09/23/2010&_rdoc=1&_fmt=high&_orig=search&_origin
=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVer
sion=0&_userid=10&md5=f3b23bb581542b5a686bad7d037e28a9&searchtype=a

http://www.ncbi.nlm.nih.gov/pubmed/2561184

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1W-4M22063-
1&_user=10&_coverDate=03/31/2007&_rdoc=1&_fmt=high&_orig=search&_origin
=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVer
sion=0&_userid=10&md5=3e010468fcf851ec3d742793f9a81998&searchtype=a

………..

For later

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WK7-4FNGGYM-
29&_user=10&_coverDate=06/05/1987&_rdoc=1&_fmt=high&_orig=search&_origin
=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVer
sion=0&_userid=10&md5=c6cf3caa8e7a7003014af9a28a10ea78&searchtype=a

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1W-4M22063-
1&_user=10&_coverDate=03/31/2007&_rdoc=1&_fmt=high&_orig=search&_origin
=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVer
sion=0&_userid=10&md5=3e010468fcf851ec3d742793f9a81998&searchtype=a

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC206685/pdf/jbacter00060-0292.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1225781/pdf/biophysj00085-0248.pdf
https://www.lablife.org/g?a=seqa&id=vdb_g2.EHBOxirdwxdkziWnuZpJgRxA.hE-
_sequence_58f4805fbd3b34e20c0843369ceb4ae9fc4a4b07_10

http://www.neb.com/nebecomm/ManualFiles/manualE8000.pdf