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Phase I - Functionalization of compounds
Stable Identifier
R-HSA-211945
Type
Pathway
Species
Homo sapiens
Compartment
cytosol
,
mitochondrial inner membrane
,
mitochondrial outer membrane
,
mitochondrial matrix
,
endoplasmic reticulum membrane
,
endoplasmic reticulum lumen
ReviewStatus
5/5
Locations in the PathwayBrowser
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Metabolism (Homo sapiens)
Biological oxidations (Homo sapiens)
Phase I - Functionalization of compounds (Homo sapiens)
General
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Phase 1 of metabolism is concerned with
functionalization
, that is the introduction or exposure of functional groups on the chemical structure of a compound. This provides a 'handle' for phase 2 conjugating species with which to react with. Many xenobiotics are lipophilic and almost chemically inert (e.g. PAHs) so would not necessarily undergo a phase 2 reaction. Making them more chemically reactive would facilitate their excretion but also increases their chance of reacting with cellular macromolecules (e.g. proteins, DNA). There is a fine balance between producing a more reactive metabolite and conjugation reactions.
There are two groups of enzymes in phase 1 - oxidoreductases and hydrolases. Oxidoreductases introduce an oxygen atom into or remove electrons from their substrates. The major oxidoreductase enzyme system is called the P450 monooxygenases. Other systems include flavin-containing monooxygenases (FMO), cyclooxygenases (COX) and monoamine oxidases (MAO). Hydrolases hydrolyse esters, amides, epoxides and glucuronides.
Literature References
PubMed ID
Title
Journal
Year
12369887
The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans
Danielson, PB
Curr Drug Metab
2002
17125408
Involvement of enzymes other than CYPs in the oxidative metabolism of xenobiotics
Baltes, E
,
Whomsley, R
,
Strolin Benedetti, M
Expert Opin Drug Metab Toxicol
2006
16584116
Cytochrome P450s and other enzymes in drug metabolism and toxicity
Guengerich, FP
AAPS J
2006
Participants
Events
Cytochrome P450 - arranged by substrate type
(Homo sapiens)
FMO oxidises nucleophiles
(Homo sapiens)
COX reactions
(Homo sapiens)
Amine Oxidase reactions
(Homo sapiens)
Ethanol oxidation
(Homo sapiens)
ALD3A1 oxidises 4HPCP to CXPA
(Homo sapiens)
CES1 trimer.CES2 hydrolyse COCN to BEG
(Homo sapiens)
EPHX1 hydrates BaP4,5O to BaP4,5-DHD
(Homo sapiens)
AOC1 deaminates Hist
(Homo sapiens)
AOC2 deaminates TYR
(Homo sapiens)
AOC3 deaminates BZAM
(Homo sapiens)
AADAC deacetylates PHEN
(Homo sapiens)
BPHL hydrolyses VACV to ACV
(Homo sapiens)
CMBL hydrolyses OM to OLMS
(Homo sapiens)
MARC1,MARC2 reduce N-hydroxylated compounds
(Homo sapiens)
NQO2:FAD dimer reduces quinones to hydroquinones
(Homo sapiens)
CBR3 reduces DOX to DOXOL
(Homo sapiens)
CES3 hydrolyses CHEST to CHOL and LCFA(-)
(Homo sapiens)
Aryl hydrocarbon receptor signalling
(Homo sapiens)
CYP3A4 binds CYP3A4 inhibitors
(Homo sapiens)
CYP3A4, CYP2B6 bind ritonavir
(Homo sapiens)
Participates
as an event of
Biological oxidations (Homo sapiens)
Event Information
Go Biological Process
xenobiotic metabolic process (0006805)
Orthologous Events
Phase I - Functionalization of compounds (Bos taurus)
Phase I - Functionalization of compounds (Caenorhabditis elegans)
Phase I - Functionalization of compounds (Canis familiaris)
Phase I - Functionalization of compounds (Danio rerio)
Phase I - Functionalization of compounds (Dictyostelium discoideum)
Phase I - Functionalization of compounds (Drosophila melanogaster)
Phase I - Functionalization of compounds (Gallus gallus)
Phase I - Functionalization of compounds (Mus musculus)
Phase I - Functionalization of compounds (Plasmodium falciparum)
Phase I - Functionalization of compounds (Rattus norvegicus)
Phase I - Functionalization of compounds (Saccharomyces cerevisiae)
Phase I - Functionalization of compounds (Schizosaccharomyces pombe)
Phase I - Functionalization of compounds (Sus scrofa)
Phase I - Functionalization of compounds (Xenopus tropicalis)
Authored
Jassal, B (2008-05-19)
Reviewed
D'Eustachio, P (2008-05-28)
Created
Jassal, B (2008-02-08)
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