EC |
1.13.11.11 |
Accepted name: |
tryptophan 2,3-dioxygenase |
Reaction: |
L-tryptophan + O2 = N-formyl-L-kynurenine |
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For diagram of tryptophan catabolism, click here |
Other name(s): |
tryptophan pyrrolase (ambiguous); tryptophanase; tryptophan oxygenase; tryptamine 2,3-dioxygenase; tryptophan peroxidase; indoleamine 2,3-dioxygenase (ambiguous); indolamine 2,3-dioxygenase (ambiguous); L-tryptophan pyrrolase; TDO; L-tryptophan 2,3-dioxygenase; L-tryptophan:oxygen 2,3-oxidoreductase (decyclizing) |
Systematic name: |
L-tryptophan:oxygen 2,3-oxidoreductase (ring-opening) |
Comments: |
A protohemoprotein. In mammals, the enzyme appears to be located only in the liver. This enzyme, together with EC 1.13.11.52, indoleamine 2,3-dioxygenase, catalyses the first and rate-limiting step in the kynurenine pathway, the major pathway of tryptophan metabolism [5]. The enzyme is specific for tryptophan as substrate, but is far more active with L-tryptophan than with D-tryptophan [2]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9014-51-1 |
References: |
1. |
Uchida, K., Shimizu, T., Makino, R., Sakaguchi, K., Iizuka, T., Ishimura, Y., Nozawa, T. and Hatano, M. Magnetic and natural circular dichroism of L-tryptophan 2,3-dioxygenases and indoleamine 2,3-dioxygenase. I. Spectra of ferric and ferrous high spin forms. J. Biol. Chem. 258 (1983) 2519–2525. [PMID: 6600455] |
2. |
Ren, S., Liu, H., Licad, E. and Correia, M.A. Expression of rat liver tryptophan 2,3-dioxygenase in Escherichia coli: structural and functional characterization of the purified enzyme. Arch. Biochem. Biophys. 333 (1996) 96–102. [DOI] [PMID: 8806758] |
3. |
Leeds, J.M., Brown, P.J., McGeehan, G.M., Brown, F.K. and Wiseman, J.S. Isotope effects and alternative substrate reactivities for tryptophan
2,3-dioxygenase. J. Biol. Chem. 268 (1993) 17781–17786. [PMID: 8349662] |
4. |
Dang, Y., Dale, W.E. and Brown, O.R. Comparative effects of oxygen on indoleamine 2,3-dioxygenase and
tryptophan 2,3-dioxygenase of the kynurenine pathway. Free Radic. Biol. Med. 28 (2000) 615–624. [DOI] [PMID: 10719243] |
5. |
Littlejohn, T.K., Takikawa, O., Truscott, R.J. and Walker, M.J. Asp274 and His346 are essential for heme binding and catalytic function of human indoleamine 2,3-dioxygenase. J. Biol. Chem. 278 (2003) 29525–29531. [DOI] [PMID: 12766158] |
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[EC 1.13.11.11 created 1961 as EC 1.11.1.4, deleted 1964, reinstated 1965 as EC 1.13.1.12, transferred 1972 to EC 1.13.11.11, modified 1989, modified 2006] |
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EC |
1.14.99.59 |
Accepted name: |
tryptamine 4-monooxygenase |
Reaction: |
tryptamine + reduced acceptor + O2 = 4-hydroxytryptamine + acceptor + H2O |
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For diagram of psilocybin biosynthesis, click here |
Glossary: |
psilocybin = 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl phosphate
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Other name(s): |
PsiH |
Systematic name: |
tryptamine,hydrogen-donor:oxygen oxidoreductase (4-hydroxylating) |
Comments: |
A cytochrome P-450 (heme-thiolate) protein isolated from the fungus Psilocybe cubensis. Involved in the biosynthesis of the psychoactive compound psilocybin. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Fricke, J., Blei, F. and Hoffmeister, D. Enzymatic synthesis of psilocybin. Angew. Chem. Int. Ed. Engl. 56 (2017) 12352–12355. [DOI] [PMID: 28763571] |
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[EC 1.14.99.59 created 2017] |
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EC |
2.1.1.4 |
Accepted name: |
acetylserotonin O-methyltransferase |
Reaction: |
S-adenosyl-L-methionine + N-acetylserotonin = S-adenosyl-L-homocysteine + melatonin |
Glossary: |
melatonin = N-acetyl-5-methoxytryptamine
serotonin = 5-hydroxytryptamine
tryptamine = 2-(1H-indol-3-yl)ethanamine |
Other name(s): |
hydroxyindole methyltransferase; hydroxyindole O-methyltransferase; N-acetylserotonin O-methyltransferase; acetylserotonin methyltransferase |
Systematic name: |
S-adenosyl-L-methionine:N-acetylserotonin O-methyltransferase |
Comments: |
Some other hydroxyindoles also act as acceptor, but more slowly. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9029-77-0 |
References: |
1. |
Axelrod, J. and Weissbach, H. Purification and properties of hydroxyindole-O-methyl transferase. J. Biol. Chem. 236 (1961) 211–213. [PMID: 13685335] |
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[EC 2.1.1.4 created 1961] |
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EC |
2.1.1.49 |
Accepted name: |
amine N-methyltransferase |
Reaction: |
S-adenosyl-L-methionine + an amine = S-adenosyl-L-homocysteine + a methylated amine |
Other name(s): |
nicotine N-methyltransferase; tryptamine N-methyltransferase; arylamine N-methyltransferase; tryptamine methyltransferase |
Systematic name: |
S-adenosyl-L-methionine:amine N-methyltransferase |
Comments: |
An enzyme of very broad specificity; many primary, secondary and tertiary amines can act as acceptors, including tryptamine, aniline, nicotine and a variety of drugs and other xenobiotics. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 51377-47-0, 111694-10-1 |
References: |
1. |
Ansher, S.S. and Jakoby, W.B. Amine N-methyltransferases from rabbit liver. J. Biol. Chem. 261 (1986) 3996–4001. [PMID: 3949799] |
2. |
Crooks, P.A., Godin, C.S., Damani, L.A., Ansher, S.S. and Jakoby, W.B. Formation of quaternary amines by N-methylation of azaheterocycles with homogeneous amine N-methyltransferases. Biochem. Pharmacol. 37 (1988) 1673–1677. [DOI] [PMID: 3377829] |
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[EC 2.1.1.49 created 1976, modified 1990 (EC 2.1.1.81 created 1989, incorporated 1990)] |
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EC |
2.1.1.345 |
Accepted name: |
psilocybin synthase |
Reaction: |
2 S-adenosyl-L-methionine + 4-hydroxytryptamine 4-phosphate = 2 S-adenosyl-L-homocysteine + psilocybin (overall reaction) (1a) S-adenosyl-L-methionine + 4-hydroxytryptamine 4-phosphate = S-adenosyl-L-homocysteine + 4-hydroxy-N-methyltryptamine 4-phosphate (1b) S-adenosyl-L-methionine + 4-hydroxy-N-methyltryptamine 4-phosphate = S-adenosyl-L-homocysteine + psilocybin |
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For diagram of psilocybin biosynthesis, click here |
Glossary: |
psilocybin = 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl phosphate |
Other name(s): |
PsiM |
Systematic name: |
S-adenosyl-L-methionine:4-hydroxytryptamine-4-phosphate N,N-dimethyltransferase |
Comments: |
Isolated from the fungus Psilocybe cubensis. The product, psilocybin, is a psychoactive compound. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Fricke, J., Blei, F. and Hoffmeister, D. Enzymatic synthesis of psilocybin. Angew. Chem. Int. Ed. Engl. 56 (2017) 12352–12355. [DOI] [PMID: 28763571] |
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[EC 2.1.1.345 created 2017] |
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EC |
2.3.1.87 |
Accepted name: |
aralkylamine N-acetyltransferase |
Reaction: |
acetyl-CoA + a 2-arylethylamine = CoA + an N-acetyl-2-arylethylamine |
Other name(s): |
serotonin acetyltransferase; serotonin acetylase; arylalkylamine N-acetyltransferase; serotonin N-acetyltransferase; AANAT; melatonin rhythm enzyme |
Systematic name: |
acetyl-CoA:2-arylethylamine N-acetyltransferase |
Comments: |
Narrow specificity towards 2-arylethylamines, including serotonin (5-hydroxytryptamine), tryptamine, 5-methoxytryptamine and phenylethylamine. This is the penultimate enzyme in the production of melatonin (5-methoxy-N-acetyltryptamine) and controls its synthesis (cf. EC 2.1.1.4, acetylserotonin O-methyltransferase). Differs from EC 2.3.1.5 arylamine N-acetyltransferase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 92941-56-5 |
References: |
1. |
Voisin, P., Namboodiri, M.A.A. and Klein, D.C. Arylamine N-acetyltransferase and arylalkylamine N-acetyltransferase in the mammalian pineal gland. J. Biol. Chem. 259 (1984) 10913–10918. [PMID: 6469990] |
2. |
Ferry, G., Loynel, A., Kucharczyk, N., Bertin, S., Rodriguez, M., Delagrange, P., Galizzi, J.P., Jacoby, E., Volland, J.P., Lesieur, D., Renard, P., Canet, E., Fauchere, J.L. and Boutin, J.A. Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. J. Biol. Chem. 275 (2000) 8794–8805. [DOI] [PMID: 10722724] |
3. |
Khalil, E.M. and Cole, P.A. A potent inhibitor of the melatonin rhythm enzyme. J. Am. Chem. Soc. 120 (1998) 6195–6196. |
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[EC 2.3.1.87 created 1986, modified 2005] |
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EC |
2.7.1.222 |
Accepted name: |
4-hydroxytryptamine kinase |
Reaction: |
ATP + 4-hydroxytryptamine = ADP + 4-hydroxytryptamine 4-phosphate |
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For diagram of psilocybin biosynthesis, click here |
Glossary: |
psilocybin = 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl phosphate |
Other name(s): |
PsiK |
Systematic name: |
ATP:4-hydroxytryptamine 4-phosphotransferase |
Comments: |
Also acts on 4-hydroxy-L-tryptophan in vitro. Isolated from the fungus Psilocybe cubensis. Involved in the biosynthesis of the psychoactive compound psilocybin. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Fricke, J., Blei, F. and Hoffmeister, D. Enzymatic synthesis of psilocybin. Angew. Chem. Int. Ed. Engl. 56 (2017) 12352–12355. [DOI] [PMID: 28763571] |
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[EC 2.7.1.222 created 2017] |
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EC |
4.1.1.28 |
Accepted name: |
aromatic-L-amino-acid decarboxylase |
Reaction: |
(1) L-dopa = dopamine + CO2 (2) 5-hydroxy-L-tryptophan = 5-hydroxytryptamine + CO2 |
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For diagram of dopa biosynthesis, click here and for diagram of indole and ipecac alkaloid biosynthesis, click here |
Glossary: |
dopamine = 4-(2-aminoethyl)benzene-1,2-diol
L-dopa = 3,4-dihydroxyphenylalanine |
Other name(s): |
DOPA decarboxylase; tryptophan decarboxylase; hydroxytryptophan decarboxylase; L-DOPA decarboxylase; aromatic amino acid decarboxylase; 5-hydroxytryptophan decarboxylase; aromatic-L-amino-acid carboxy-lyase (tryptamine-forming) |
Systematic name: |
aromatic-L-amino-acid carboxy-lyase |
Comments: |
A pyridoxal-phosphate protein. The enzyme also acts on some other aromatic L-amino acids, including L-tryptophan, L-tyrosine and L-phenylalanine. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9042-64-2 |
References: |
1. |
Christenson, J.G., Dairman, W. and Udenfriend, S. On the identity of DOPA decarboxylase and 5-hydroxytryptophan decarboxylase (immunological titration-aromatic L-amino acid decarboxylase-serotonin-dopamine-norepinephrine). Proc. Natl. Acad. Sci. USA 69 (1972) 343–347. [DOI] [PMID: 4536745] |
2. |
Lovenberg, W., Weissbach, H. and Udenfriend, S. Aromatic L-amino acid decarboxylase. J. Biol. Chem. 237 (1962) 89–93. [PMID: 14466899] |
3. |
McGilvery, R.W. and Cohen, P.P. The decarboxylation of L-phenylalanine by Streptococcus faecalis R. J. Biol. Chem. 174 (1948) 813–816. [PMID: 18871240] |
4. |
Sekeris, C.E. Zur Tyrosinstoffwechsel der Insekten. XII. Reinigung, Eigenschaften und Substratspezifität der DOPA-Decarboxylase. Hoppe-Seyler's Z. Physiol. Chem. 332 (1963) 70–78. [PMID: 14054806] |
5. |
Weissbach, H., Bogdanski, D.F., Redfield, B.G. and Udenfriend, S. Studies on the effect of vitamin B6 on 5-hydroxytryptamine (serotonin) formation. J. Biol. Chem. 227 (1957) 617–624. [PMID: 13462983] |
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[EC 4.1.1.28 created 1961 (EC 4.1.1.26 and EC 4.1.1.27 both created 1961 and incorporated 1972)] |
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EC |
4.1.1.105 |
Accepted name: |
L-tryptophan decarboxylase |
Reaction: |
L-tryptophan = tryptamine + CO2 |
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For diagram of psilocybin biosynthesis, click here |
Other name(s): |
psiD (gene name); TDC (gene name) |
Systematic name: |
L-tryptophan carboxy-lyase |
Comments: |
The enzyme has been characterized from bacteria, plants, and fungi. Unlike EC 4.1.1.28, aromatic-L-amino-acid decarboxylase, this enzyme is specific for L-tryptophan. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Noe, W., Mollenschott, C. and Berlin, J. Tryptophan decarboxylase from Catharanthus roseus cell suspension cultures: purification, molecular and kinetic data of the homogenous protein. Plant Mol. Biol. 3 (1984) 281–288. [DOI] [PMID: 24310513] |
2. |
Buki, K.G., Vinh, D.Q. and Horvath, I. Partial purification and some properties of tryptophan decarboxylase from a Bacillus strain. Acta Microbiol Hung 32 (1985) 65–73. [PMID: 4036551] |
3. |
Nakazawa, H., Kumagai, H. and Yamada, H. Constitutive aromatic L-amino acid decarboxylase from Micrococcus percitreus. Biochem. Biophys. Res. Commun. 61 (1974) 75–82. [DOI] [PMID: 4441405] |
4. |
Lopez-Meyer, M. and Nessler, C.L. Tryptophan decarboxylase is encoded by two autonomously regulated genes in Camptotheca acuminata which are differentially expressed during development and stress. Plant J. 11 (1997) 1167–1175. [DOI] [PMID: 9225462] |
5. |
Fricke, J., Blei, F. and Hoffmeister, D. Enzymatic synthesis of psilocybin. Angew. Chem. Int. Ed. Engl. 56 (2017) 12352–12355. [DOI] [PMID: 28763571] |
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[EC 4.1.1.105 created 2017] |
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EC |
4.3.3.2 |
Accepted name: |
strictosidine synthase |
Reaction: |
3-α(S)-strictosidine + H2O = tryptamine + secologanin |
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For diagram of indole and ipecac alkaloid biosynthesis, click here |
Other name(s): |
strictosidine synthetase; STR; 3-α(S)-strictosidine tryptamine-lyase |
Systematic name: |
3-α(S)-strictosidine tryptamine-lyase (secologanin-forming) |
Comments: |
Catalyses a Pictet-Spengler reaction between the aldehyde group of secologanin and the amino group of tryptamine [4,5]. Involved in the biosynthesis of the monoterpenoid indole alkaloids. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 69669-72-3 |
References: |
1. |
Treimer, J.K. and Zenk, M.H. Purification and properties of strictosidine synthase, the key enzyme in indole alkaloid formation. Eur. J. Biochem. 101 (1979) 225–233. [DOI] [PMID: 510306] |
2. |
Kutchan, T.M. Strictosidine: from alkaloid to enzyme to gene. Phytochemistry 32 (1993) 493–506. [DOI] [PMID: 7763429] |
3. |
de Waal, A., Meijer, A.H. and Verpoorte, R. Strictosidine synthase from Catharanthus roseus: purification and characterization of multiple forms. Biochem. J. 306 (1995) 571–580. [PMID: 7887913] |
4. |
Ruppert, M., Woll, J., Giritch, A., Genady, E., Ma, X. and Stöckigt, J. Functional expression of an ajmaline pathway-specific esterase from
Rauvolfia in a novel plant-virus expression system. Planta 222 (2005) 888–898. [DOI] [PMID: 16133216] |
5. |
McCoy, E., Galan, M.C. and O'Connor, S.E. Substrate specificity of strictosidine synthase. Bioorg. Med. Chem. Lett. 16 (2006) 2475–2478. [DOI] [PMID: 16481164] |
6. |
Ma, X., Panjikar, S., Koepke, J., Loris, E. and Stöckigt, J. The structure of Rauvolfia serpentina strictosidine synthase is a novel
six-bladed β-propeller fold in plant proteins. Plant Cell 18 (2006) 907–920. [DOI] [PMID: 16531499] |
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[EC 4.3.3.2 created 1990] |
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