Phase 1 - Functionalization of compounds (Homo sapiens)

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Curation Tags

Description

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.

Ontology Tags

 

Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
72910view15:13, 14 December 2013EgonwArgh...
72908view15:12, 14 December 2013EgonwFixed the Uniprot-TrEMBL data sources.
72906view15:09, 14 December 2013EgonwUpdated the UniProt data source with UniProt/TrEMBL.
42095view21:56, 4 March 2011MaintBotAutomatic update
39905view05:55, 21 January 2011MaintBotNew pathway

External references

View all...
NameTypeDatabase referenceComment
N-

Acetylbenzoquinoneim ine

Metabolite29132 (ChEBI)
aldehyde

dehydrogenase, mitochondrial, tetramer

ComplexREACT_2466 (Reactome)
19-

hydroxyprostaglandin H2

MetaboliteREACT_14313 (Reactome)
FMO3 (FAD

cofactor)

ComplexREACT_14498 (Reactome)
Leukotriene B4 Metabolite15647 (ChEBI)
4-Aminobiphenyl Metabolite1784 (ChEBI)
Cytochrome P450

4F2

ProteinP78329 (Uniprot-TrEMBL)
Cytochrome P450

26

ProteinO43174 (Uniprot-TrEMBL)
NADPH Metabolite16474 (ChEBI)
Phenylacetaldehyde Metabolite16424 (ChEBI)
Thromboxane A2 Metabolite15627 (ChEBI)
Paclitaxel Metabolite45863 (ChEBI)
Cytochrome P450

4F3

ProteinQ08477 (Uniprot-TrEMBL)
Chloride Metabolite17996 (ChEBI)
Prostaglandin H2 Metabolite15554 (ChEBI)
Calcitriol Metabolite17823 (ChEBI)
electron Metabolite10545 (ChEBI)
3-hydroxypalmitate Metabolite37248 (ChEBI)
TBXAS1 ProteinP24557 (Uniprot-TrEMBL)
MAOB-FAD

complex

ComplexREACT_4664 (Reactome)
Cytochrome P450

4F8

ProteinP98187 (Uniprot-TrEMBL)
Spermidine Metabolite16610 (ChEBI)
H2O Metabolite15377 (ChEBI)
Dextromethorphan Metabolite4470 (ChEBI)
Prostacyclin Metabolite15552 (ChEBI)
Paraxanthine Metabolite25858 (ChEBI)
H+ Metabolite15378 (ChEBI)
Acetaminophen (TN

TYLENOL)

Metabolite46195 (ChEBI)
NADP+ Metabolite18009 (ChEBI)
Hydrogen bromide Metabolite47266 (ChEBI)
PTGIS ProteinQ16647 (Uniprot-TrEMBL)
CYP2R1 ProteinQ6VVX0 (Uniprot-TrEMBL)
Estrone Metabolite17263 (ChEBI)
Cytochrome P450

26C1

ProteinQ6V0L0 (Uniprot-TrEMBL)
11-

deoxycorticosterone

Metabolite16973 (ChEBI)
Indole Metabolite16881 (ChEBI)
25-

hydroxycholesterol

Metabolite42977 (ChEBI)
Trimethyamine N-

oxide

Metabolite15724 (ChEBI)
CYP11A1 ProteinP05108 (Uniprot-TrEMBL)
Prostaglandin G2 Metabolite27647 (ChEBI)
Cholest-5-ene-

3beta,7alpha,25- triol

Metabolite37623 (ChEBI)
4-

Hydroxyphenylacetalde hyde

Metabolite15621 (ChEBI)
lanosterol Metabolite16521 (ChEBI)
3-acetamidopropanal Metabolite30322 (ChEBI)
Corticosterone Metabolite16827 (ChEBI)
ATP Metabolite15422 (ChEBI)
CYP17A1 ProteinP05093 (Uniprot-TrEMBL)
pyrophosphate Metabolite29888 (ChEBI)
Progesterone Metabolite17026 (ChEBI)
5-hydroxyomeprazole MetaboliteREACT_14076 (Reactome)
4,4-

dimethylcholesta-8 (9),14,24-trien- 3beta-ol

MetaboliteREACT_10253 (Reactome)
4-hydroxyphenytoin MetaboliteREACT_14384 (Reactome)
20alpha,22beta

dihydroxycholesterol

Metabolite1294 (ChEBI)
N-Hydroxy-4-

aminobiphenyl

Metabolite16580 (ChEBI)
Cortisol Metabolite17650 (ChEBI)
Halothane Metabolite5615 (ChEBI)
Pregnenolone Metabolite16581 (ChEBI)
Trifluoroacetylchloride Metabolite29138 (ChEBI)
24-

hydroxycholesterol

Metabolite34310 (ChEBI)
Hydrogen Metabolite18276 (ChEBI)
Cholesterol Metabolite16113 (ChEBI)
Phenol Metabolite15882 (ChEBI)
CYP11B1 ProteinP15538 (Uniprot-TrEMBL)
Vitamin D3 Metabolite28940 (ChEBI)
CYP51A1 ProteinQ16850 (Uniprot-TrEMBL)
1,24,25-

trihydroxyvitamin D3

MetaboliteREACT_14412 (Reactome)
Estradiol-17beta Metabolite16469 (ChEBI)
9-cis-retinoic acid MetaboliteREACT_13921 (Reactome)
4-hydroxyestradiol-

17beta

MetaboliteREACT_14175 (Reactome)
4-hydroxy-all-trans-

retinoic acid

MetaboliteREACT_14163 (Reactome)
Cytochrome P450

7A1

ProteinP22680 (Uniprot-TrEMBL)
19-hydroxyarachidonic

acid

MetaboliteREACT_14524 (Reactome)
7 alpha-

hydroxycholesterol

Metabolite17500 (ChEBI)
Cytochrome P450

2W1

ProteinQ8TAV3 (Uniprot-TrEMBL)
Cholest-5-ene-3beta,

7alpha,24(S)-triol

Metabolite37640 (ChEBI)
Cytochrome P450

4F11

ProteinQ9HBI6 (Uniprot-TrEMBL)
Cytochrome P450

7B1

ProteinO75881 (Uniprot-TrEMBL)
Trimethylamine Metabolite18139 (ChEBI)
17alpha-

hydroxypregnenolone

Metabolite28750 (ChEBI)
FMO2 (FAD, Mg2+

cofactors)

ComplexREACT_14675 (Reactome)
Formate Metabolite30751 (ChEBI)
PGHS2 dimer ComplexREACT_2322 (Reactome)
Cytochrome P450

1B1

ProteinQ16678 (Uniprot-TrEMBL)
H2O2 Metabolite16240 (ChEBI)
Cytochrome P450

27

ProteinQ02318 (Uniprot-TrEMBL)
5-

Hydroxyindoleacetalde hyde

Metabolite50157 (ChEBI)
CYP19A1 ProteinP11511 (Uniprot-TrEMBL)
Spermidine Oxidase

(SMOX)

UnknownREACT_14616 (Reactome)
4-Androstene-3, 17-

dione

Metabolite16422 (ChEBI)
3-aminopropanal Metabolite18090 (ChEBI)
Cytochrome P450

39A1

ProteinQ9NYL5 (Uniprot-TrEMBL)
AMP Metabolite16027 (ChEBI)
11-deoxycortisol Metabolite28324 (ChEBI)
CoA-SH Metabolite15346 (ChEBI)
CYP21A2 ProteinP08686 (Uniprot-TrEMBL)
Acetyl-coenzyme A

synthetase, cytoplasmic

ProteinQ9NR19 (Uniprot-TrEMBL)
Cytochrome p450

46A1

ProteinQ9Y6A2 (Uniprot-TrEMBL)
ACSS1 ProteinQ9NUB1 (Uniprot-TrEMBL)
Isocaproic aldehyde Metabolite17998 (ChEBI)
Oxygen Metabolite15379 (ChEBI)
27-

hydroxycholesterol

Metabolite17703 (ChEBI)
Hydroxycoumarin Metabolite27510 (ChEBI)
CYP11B2 ProteinP19099 (Uniprot-TrEMBL)
Cytochrome P450

2B6

ProteinP20813 (Uniprot-TrEMBL)
Cytochrome P450

8B1

ProteinQ9UNU6 (Uniprot-TrEMBL)
Aflatoxin exo-8,9-

oxide

Metabolite2505 (ChEBI)
4-cholesten-7alpha,

12alpha-diol-3-one

Metabolite28477 (ChEBI)
Formaldehyde Metabolite16842 (ChEBI)
4-cholesten-7alpha,

12alpha,24(S)-triol-3- one

MetaboliteREACT_10249 (Reactome)
Caffeine Metabolite27732 (ChEBI)
4-cholesten-7alpha-

ol-3-one

Metabolite17899 (ChEBI)
CYPIA2 ProteinP05177 (Uniprot-TrEMBL)
4-cholesten-7alpha,

24(S)-diol-3-one

MetaboliteREACT_10645 (Reactome)
2-Chloroethylene

oxide

Metabolite29129 (ChEBI)
4-cholesten-7alpha,

12alpha,27-triol-3- one

MetaboliteREACT_10863 (Reactome)
Acetaldehyde Metabolite15343 (ChEBI)
4-cholesten-7alpha,

27-diol-3-one

MetaboliteREACT_10821 (Reactome)
Carbon tetrachloride Metabolite27385 (ChEBI)
Arachidonate Metabolite15843 (ChEBI)
Trichloromethyl

radical

UnknownREACT_4348 (Reactome)
cis-EET MetaboliteREACT_14302 (Reactome)
Vinyl chloride Metabolite28509 (ChEBI)
Cytochrome P450

2J2

ProteinP51589 (Uniprot-TrEMBL)
Benzene Metabolite16716 (ChEBI)
Dodecylcarboxylate Metabolite30805 (ChEBI)
Ethanol Metabolite16236 (ChEBI)
omega-

Hydroxydodecanoic acid

Metabolite39567 (ChEBI)
Cytochrome P450

2E1

ProteinP05181 (Uniprot-TrEMBL)
Cytochrome P450

4A11

ProteinQ02928 (Uniprot-TrEMBL)
Calcidiol MetaboliteREACT_14066 (Reactome)
12-hydroxy-

5,8,11,14- eicosatetraenoic acid

MetaboliteREACT_14354 (Reactome)
1,25-dihydroxyvitamin

D3

MetaboliteREACT_14555 (Reactome)
Cytochrome P450

4B1

ProteinP13584 (Uniprot-TrEMBL)
CYP24A1 ProteinQ07973 (Uniprot-TrEMBL)
18-

hydroxyarachidonate

MetaboliteREACT_14303 (Reactome)
CYP27B1 ProteinO15528 (Uniprot-TrEMBL) The start coordinate is not yet known
Cytochrome P450

4F12

ProteinQ9HCS2 (Uniprot-TrEMBL)
4-hydroxy-9-cis-

retinoic acid

MetaboliteREACT_14157 (Reactome)
4-hydroxytolbutamide MetaboliteREACT_14607 (Reactome)
All-trans-retinoic

acid

Metabolite15367 (ChEBI)
Testosterone Metabolite17347 (ChEBI)
Cytochrome P450

26B1

ProteinQ9NR63 (Uniprot-TrEMBL)
Cytochrome P450

2C18

ProteinP33260 (Uniprot-TrEMBL)
CYP2S1 UnknownREACT_13891 (Reactome)
N-demethylated

loperaminde

MetaboliteREACT_13974 (Reactome)
Cytochrome P450

2U1-1

ProteinQ7Z449-1 (Uniprot-TrEMBL)
6beta-

hydroxytestosterone

MetaboliteREACT_14369 (Reactome)
Oxindole Metabolite31697 (ChEBI)
Cytochrome P450

2A13

ProteinQ16696 (Uniprot-TrEMBL)
CYP3A43 UnknownREACT_14617 (Reactome)
4-

hydroxycyclophospham ide

MetaboliteREACT_14339 (Reactome)
3,16-

dihydroxypalmitate

MetaboliteREACT_14525 (Reactome)
Cytochrome P450

1A1

ProteinP04798 (Uniprot-TrEMBL)
Methimazole MetaboliteREACT_14663 (Reactome)
Tolbutamide MetaboliteREACT_14612 (Reactome)
Tamoxifen N-oxide MetaboliteREACT_14315 (Reactome)
Cytochrome P450

2C8

ProteinP10632 (Uniprot-TrEMBL)
Tamoxifen Metabolite41774 (ChEBI)
Cytochrome P450

3A7

ProteinP24462 (Uniprot-TrEMBL)
Methimazole S-

oxide

MetaboliteREACT_13855 (Reactome)
4-hydroxydebrisoquine MetaboliteREACT_14465 (Reactome)
FMO1 (FAD

cofactor)

ComplexREACT_14390 (Reactome)
6-hydroxypaclitaxel MetaboliteREACT_14215 (Reactome)
PTGS dimers UnknownREACT_20049 (Reactome)
Cyclophosphamide Metabolite4026 (ChEBI)
MAOA-FAD

complex

ComplexREACT_5113 (Reactome)
Debrisoquine MetaboliteREACT_14596 (Reactome)
NH3 Metabolite16134 (ChEBI)
Ethylene Metabolite18153 (ChEBI)
Tyramine Metabolite15760 (ChEBI)
Cytochrome P450

2C19

ProteinP33261 (Uniprot-TrEMBL)
5-Hydroxytryptamine Metabolite28790 (ChEBI)
Cytochrome P450

3A5

ProteinP20815 (Uniprot-TrEMBL)
2-Phenylethylamine Metabolite18397 (ChEBI)
Cytochrome P450

2F1

ProteinP24903 (Uniprot-TrEMBL)
N-acetylspermidine Metabolite17927 (ChEBI)
Coumarin Metabolite28794 (ChEBI)
N-acetylspermine Metabolite17312 (ChEBI)
3-methylindole Metabolite9171 (ChEBI)
Spermine Metabolite15746 (ChEBI)
Ethylene oxide Metabolite27561 (ChEBI)
Putrescine Metabolite17148 (ChEBI)
Omeprazole MetaboliteREACT_14364 (Reactome)
PAO-FAD complex ComplexREACT_3389 (Reactome)
Cytochrome P450

2A6

ProteinP11509 (Uniprot-TrEMBL)
NAD+ Metabolite15846 (ChEBI)
Aflatoxin B1 Metabolite2504 (ChEBI)
NADH Metabolite16908 (ChEBI)
Phenytoin MetaboliteREACT_13828 (Reactome)
Acetyl-CoA Metabolite15351 (ChEBI)
CYP2D6 ProteinP10635 (Uniprot-TrEMBL)
Acetate Metabolite15366 (ChEBI)
3-methyleneindolenine MetaboliteREACT_14274 (Reactome)
aldehyde

dehydrogenase 1A1 tetramer

ComplexREACT_5868 (Reactome)
Loperamide Metabolite6532 (ChEBI)
alcohol

dehydrogenase complex

UnknownREACT_21845 (Reactome)
Cytochrome P450

2C9

ProteinP11712 (Uniprot-TrEMBL)
20-OH-leukotriene B4 Metabolite15646 (ChEBI)
Cytochrome P450

3A4

ProteinP08684 (Uniprot-TrEMBL)
Dextrorphan Metabolite29133 (ChEBI)
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