Lecture notes
Biochemistry
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- University Of East Anglia
Lecture notes for Biochemistry
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Cytochrome p450:--Enzymes that catalyse monooxygenation of structurally diverse
compounds. such as cholesreol, steroid, hormones and fatty acids, dugs,
food additives, pesticides.
--Called cytochromes becuase they contain a cofactor which is the heme
group/cofactor.
--Called P450 becuase thats the peak maximum of absorbotion of the
redcuced enzyme + CO on the UV-vis spectra. P450 = Pigment with
absorbance at 450 nm.
Cytochrome P450 catalyse Monooxygenation( incorporation of one of two
oxygen atoms from O2 into an organic molecule R3CH):
--R3CH + O2 + NADPH + H(+) --> R3COH +NADP+ +H2O
--R3CH is hydrophobic / lipophilic compound and R3COH is less hydrophobic
and more hydrophilic than R3CH.
NADPH/NADP+ is a 2e- Redox Co-Substrate:
--NADP+ + 2e- + H+ = NADPH
Class ii cytochrome p450:
-- Found in the endoplasmic reticulum withtin hepatocytes, in renal
cellas and cells of th respiratory tract. These are the class ii
cyrichrime P450 enzymes:
--In NADPH cytochrome P450 Oxi doreductase: NADPH is oxidised to NADP+,
the electorns are used to convert FAD to FMN which passes the electrons
to the cytochtrome P450. Cytochrome p450 uses it for the monooxygenation
of R3CH + O2 ---> R3COH + H2O
Class i Cytochrome p450:
--Found in the inner miochrondrial membrane:
-- In Ferredoxin Reductase:NADPH oxidised to NADP+, electrons are passed
to iron-sulfure cluster in ferrodoxin, these pass elecrons to heme group
of cytochrome p450 which uses the electons for the monooxygenation of
R3CH + O2 ---> R3COH + H2O
--The gene is alternatively spliced to produce a superfamily of different
isoforms of cytochrome p450.
Cytochrome P450 nomenclature:
---Family --> Sub family --> Specific isoform e.g. CYP1A1
--In humans there are 57 cytochrome P450, 7 cytochrome P450 are
mitochrondrial, the rest are found in the endoplasmic reticulum.
--The cyp450 with high substarte specificity process cholesterol,
steroids, prostaglndins and fatty acids. They are responsible for
changing endogeous molecules into another molecule.
Cyp450 differences in metabolism of endogenous and exogenous molecules:
--CYP450 that process exogenous molecules are less substrate specific
than CYP450 that process endogenous molecules.
--Families of CYP450 that process endogenous molecules: CYP1, CYP2, CYP3.
--Exogenous CYP450 have a large cavernous active site in order to process
many differnt subsrates.
--Many xenobiotics are highly lipophilic and accumulate within cells
which could interfere with cellular functions. CYP450 metbolise
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