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General Information:

Id:	7,553
Diseases:	Metabolic
Organism:	Homo sapiens
Publication type:	article/cited
Reference:	Schallreuter KU et al.(1994) Defective tetrahydrobiopterin and catecholamine biosynthesis in the depigmentation disorder vitiligo Biochim. Biophys. Acta 1226: 181-192 [PMID: 8204666]

Interaction Information:

Comment	Patients with the depigmentation disorder vitiligo have a defect in the enzyme tyrosinase, which is the rate limiting enzyme in melanin biosynthesis from tyrosine via L-DOPA. (cited information)
Formal Description Interaction-ID: 74777	gene/protein TYR decreases_quantity of drug/chemical compound Tyrosine
Drugbank entries	Show/Hide entries for TYR
Drugbank DB00157	NADH not specified TYR
Drugbank DB00548	Azelaic Acid inhibitor TYR
Drugbank DB00600	Monobenzone inhibitor TYR
Drugbank DB01055	Mimosine inhibitor TYR
Drugbank DB00157	NADH not specified TYR
Drugbank DB01055	Mimosine inhibitor TYR

Comment	Patients with the depigmentation disorder vitiligo have a defect in the enzyme tyrosinase, which is the rate limiting enzyme in melanin biosynthesis from tyrosine via L-DOPA. (cited information)
Formal Description Interaction-ID: 74778	gene/protein TYR increases_quantity of drug/chemical compound 3,4-Dihydroxy-L-phenylalanine
Drugbank entries	Show/Hide entries for TYR
Drugbank DB00157	NADH not specified TYR
Drugbank DB00548	Azelaic Acid inhibitor TYR
Drugbank DB00600	Monobenzone inhibitor TYR
Drugbank DB01055	Mimosine inhibitor TYR
Drugbank DB00157	NADH not specified TYR
Drugbank DB01055	Mimosine inhibitor TYR

Comment	Patients with the depigmentation disorder vitiligo have a defect in the enzyme tyrosinase, which is the rate limiting enzyme in melanin biosynthesis from tyrosine via L-DOPA. (cited information)
Formal Description Interaction-ID: 74779	drug/chemical compound Tyrosine increases_quantity of drug/chemical compound 3,4-Dihydroxy-L-phenylalanine

Comment	Patients with the depigmentation disorder vitiligo have a defect in the enzyme tyrosinase, which is the rate limiting enzyme in melanin biosynthesis from tyrosine via L-DOPA. (cited information)
Formal Description Interaction-ID: 74780	drug/chemical compound 3,4-Dihydroxy-L-phenylalanine increases_quantity of drug/chemical compound Melanin

Comment	Patients with the depigmentation disorder vitiligo have a defect in the enzyme tyrosinase, which is the rate limiting enzyme in melanin biosynthesis from tyrosine via L-DOPA. (cited information)
Formal Description Interaction-ID: 74781	gene/protein TYR affects_activity of disease Vitiligo
Drugbank entries	Show/Hide entries for TYR
Drugbank DB00157	NADH not specified TYR
Drugbank DB00548	Azelaic Acid inhibitor TYR
Drugbank DB00600	Monobenzone inhibitor TYR
Drugbank DB01055	Mimosine inhibitor TYR
Drugbank DB00157	NADH not specified TYR
Drugbank DB01055	Mimosine inhibitor TYR

Comment	Patients with vitiligo have a 3- to 5-fold increase in GTP-cyclohydrolase I activity leading to an excessive de novo synthesis of BH4.
Formal Description Interaction-ID: 74782	disease Vitiligo increases_activity of gene/protein GCH1
Drugbank entries	Show/Hide entries for GCH1
Drugbank DB02377	Guanine inhibitor GCH1
Drugbank DB02377	Guanine inhibitor GCH1

Comment	Continuous production of 6-BH4 due to increased GTP-cyclohydrolase I activity in Vitiligo patients, leads to an accumulation of the non-enzymatic byproduct 7-tetrahydropterin in the epidermis and to an excess of norepinephrine in both the plasma and urine of these patients.
Formal Description Interaction-ID: 74826	gene/protein GCH1 increases_quantity of drug/chemical compound Tetrahydrobiopterin
Drugbank entries	Show/Hide entries for GCH1 or Tetrahydrobiopterin
Drugbank DB02377	Guanine inhibitor GCH1
Drugbank DB02377	Guanine inhibitor GCH1
Drugbank DB00360	Tetrahydrobiopterin cofactor PAH
Drugbank DB00360	Tetrahydrobiopterin cofactor NOS3
Drugbank DB00360	Tetrahydrobiopterin cofactor TH
Drugbank DB00360	Tetrahydrobiopterin cofactor TPH1

Comment	Continuous production of 6-BH4 due to increased GTP-cyclohydrolase I activity in Vitiligo patients, leads to an accumulation of the non-enzymatic byproduct 7-tetrahydropterin in the epidermis and to an excess of norepinephrine in both the plasma and urine of these patients.
Formal Description Interaction-ID: 74828	disease Vitiligo increases_quantity of drug/chemical compound Tetrahydrobiopterin
Drugbank entries	Show/Hide entries for
Drugbank DB00360	Tetrahydrobiopterin cofactor PAH
Drugbank DB00360	Tetrahydrobiopterin cofactor NOS3
Drugbank DB00360	Tetrahydrobiopterin cofactor TH
Drugbank DB00360	Tetrahydrobiopterin cofactor TPH1

Comment	Continuous production of 6-BH4 due to increased GTP-cyclohydrolase I activity in Vitiligo patients, leads to an accumulation of the non-enzymatic byproduct 7-tetrahydropterin in the epidermis and to an excess of norepinephrine in both the plasma and urine of these patients.
Formal Description Interaction-ID: 74829	disease Vitiligo increases_quantity of drug/chemical compound Noradrenaline in plasma and urine

Comment	Continuous production of 6-BH4 due to increased GTP-cyclohydrolase I activity in Vitiligo patients leads to an accumulation of the non-enzymatic byproduct 7-tetrahydropterin by decreased 4a-hydroxytetrahydrobiopterin dehydratase activity. This enzyme is essential for recycling and maintaining normal levels of 6-BH4.
Formal Description Interaction-ID: 74830	gene/protein PCBD1 decreases_quantity of drug/chemical compound 4a-Hydroxytetrahydrobiopterin
Drugbank entries	Show/Hide entries for PCBD1
Drugbank DB04400	7,8-Dihydrobiopterin not specified PCBD1
Drugbank DB04400	7,8-Dihydrobiopterin not specified PCBD1

Comment	Continuous production of 6-BH4 due to increased GTP-cyclohydrolase I activity in Vitiligo patients leads to an accumulation of the non-enzymatic byproduct 7-tetrahydropterin (4a-Hydroxytetrahydrobiopterin) by decreased 4a-hydroxytetrahydrobiopterin dehydratase activity. This enzyme is essential for recycling and maintaining normal levels of 6-BH4.
Formal Description Interaction-ID: 74831	gene/protein PCBD1 increases_quantity of drug/chemical compound Tetrahydrobiopterin
Drugbank entries	Show/Hide entries for PCBD1 or Tetrahydrobiopterin
Drugbank DB04400	7,8-Dihydrobiopterin not specified PCBD1
Drugbank DB04400	7,8-Dihydrobiopterin not specified PCBD1
Drugbank DB00360	Tetrahydrobiopterin cofactor PAH
Drugbank DB00360	Tetrahydrobiopterin cofactor NOS3
Drugbank DB00360	Tetrahydrobiopterin cofactor TH
Drugbank DB00360	Tetrahydrobiopterin cofactor TPH1

Comment	Continuous production of 6-BH4 due to increased GTP-cyclohydrolase I activity in Vitiligo patients leads to an accumulation of the non-enzymatic byproduct 7-tetrahydropterin (4a-Hydroxytetrahydrobiopterin) by decreased 4a-hydroxytetrahydrobiopterin dehydratase activity. This enzyme is essential for recycling and maintaining normal levels of 6-BH-4.
Formal Description Interaction-ID: 74832	drug/chemical compound 4a-Hydroxytetrahydrobiopterin increases_quantity of drug/chemical compound Tetrahydrobiopterin
Drugbank entries	Show/Hide entries for
Drugbank DB00360	Tetrahydrobiopterin cofactor PAH
Drugbank DB00360	Tetrahydrobiopterin cofactor NOS3
Drugbank DB00360	Tetrahydrobiopterin cofactor TH
Drugbank DB00360	Tetrahydrobiopterin cofactor TPH1

Comment	Continuous production of 6-BH4 due to increased GTP-cyclohydrolase I activity in Vitiligo patients leads to an accumulation of the non-enzymatic byproduct 7-tetrahydropterin (4a-Hydroxytetrahydrobiopterin) by decreased 4a-hydroxytetrahydrobiopterin dehydratase activity. This enzyme is essential for recycling and maintaining normal levels of 6-BH4.
Formal Description Interaction-ID: 74833	disease Vitiligo decreases_activity of gene/protein PCBD1
Drugbank entries	Show/Hide entries for PCBD1
Drugbank DB04400	7,8-Dihydrobiopterin not specified PCBD1
Drugbank DB04400	7,8-Dihydrobiopterin not specified PCBD1

Comment	Continuous production of 6-BH4 due to increased GTP-cyclohydrolase I activity in Vitiligo patients leads to an accumulation of the non-enzymatic byproduct 7-tetrahydropterin (4a-Hydroxytetrahydrobiopterin) by decreased 4a-hydroxytetrahydrobiopterin dehydratase activity. This enzyme is essential for recycling and maintaining normal levels of 6-BH4.
Formal Description Interaction-ID: 74834	disease Vitiligo increases_quantity of drug/chemical compound 4a-Hydroxytetrahydrobiopterin by decreasing GCH1 activity

Comment	7-BH4 (4a-Hydroxytetrahydrobiopterin) is a competitive inhibitor of phenylalanine hydroxylase.
Formal Description Interaction-ID: 74835	drug/chemical compound 4a-Hydroxytetrahydrobiopterin decreases_activity of gene/protein PAH in epidermis and in cultured melanocytes of vitiligo patients
Drugbank entries	Show/Hide entries for PAH
Drugbank DB00120	L-Phenylalanine not specified PAH
Drugbank DB00360	Tetrahydrobiopterin cofactor PAH
Drugbank DB00368	Norepinephrine inhibitor PAH
Drugbank DB00668	Epinephrine antagonist PAH
Drugbank DB02562	Quinonoid 7,8-Tetrahydrobiopterin not specified PAH
Drugbank DB02692	(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin not specified PAH
Drugbank DB02960	1-Carboxyethylaminomethyl-4-Aminomethylb ... not specified pah
Drugbank DB03673	Beta(2-Thienyl)Alanine not specified PAH
Drugbank DB04400	7,8-Dihydrobiopterin not specified PAH
Drugbank DB04419	Norleucine not specified PAH
Drugbank DB06262	Droxidopa inhibitor PAH
Drugbank DB00120	L-Phenylalanine not specified PAH
Drugbank DB02562	Quinonoid 7,8-Tetrahydrobiopterin not specified PAH
Drugbank DB02692	(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin not specified PAH
Drugbank DB02960	1-Carboxyethylaminomethyl-4-Aminomethylb ... not specified pah
Drugbank DB03673	Beta(2-Thienyl)Alanine not specified PAH
Drugbank DB04400	7,8-Dihydrobiopterin not specified PAH
Drugbank DB04419	Norleucine not specified PAH

Comment	Accumulation of 7-BH4 (4a-hydroxytetrahydrobiopterin) in the epidermis of patients with vitiligo blocks the supply of L-tyrosine from L-phenylalanine.
Formal Description Interaction-ID: 74836	drug/chemical compound 4a-Hydroxytetrahydrobiopterin decreases_quantity of drug/chemical compound Tyrosine via inhibition of PAH

Comment	4a-hydroxytetrahydrobiopterin dehydratase functions as activator/dimerization catalyst for the transcription factor hepatocyte nuclear factor I (HNF-I).
Formal Description Interaction-ID: 74838	gene/protein PCBD1 increases_activity of gene/protein HNF1A
Drugbank entries	Show/Hide entries for PCBD1 or HNF1A
Drugbank DB04400	7,8-Dihydrobiopterin not specified PCBD1
Drugbank DB04400	7,8-Dihydrobiopterin not specified PCBD1
Drugbank DB04419	Norleucine not specified HNF1A
Drugbank DB04419	Norleucine not specified HNF1A

Comment	HNF-I binds to a 16-base inverted palindrome on the promoters of both the tyrosinase and phenylethanolamine-N-methyl transferase (PNMT) genes.
Formal Description Interaction-ID: 74839	gene/protein HNF1A affects_expression of gene/protein TYR in melanocytes
Drugbank entries	Show/Hide entries for HNF1A or TYR
Drugbank DB04419	Norleucine not specified HNF1A
Drugbank DB04419	Norleucine not specified HNF1A
Drugbank DB00157	NADH not specified TYR
Drugbank DB00548	Azelaic Acid inhibitor TYR
Drugbank DB00600	Monobenzone inhibitor TYR
Drugbank DB01055	Mimosine inhibitor TYR
Drugbank DB00157	NADH not specified TYR
Drugbank DB01055	Mimosine inhibitor TYR

Comment	HNF-I binds to a 16-base inverted palindrome on the promoters of both the tyrosinase and phenylethanolamine-N-methyl transferase (PNMT) genes.
Formal Description Interaction-ID: 74840	gene/protein HNF1A affects_expression of gene/protein PNMT in keratinocytes
Drugbank entries	Show/Hide entries for HNF1A or PNMT
Drugbank DB04419	Norleucine not specified HNF1A
Drugbank DB04419	Norleucine not specified HNF1A
Drugbank DB01752	S-Adenosyl-L-Homocysteine not specified PNMT
Drugbank DB03468	1,2,3,4-Tetrahydro-Isoquinoline-7-Sulfon ... not specified PNMT
Drugbank DB03824	7-Iodo-1,2,3,4-Tetrahydro-Isoquinoline not specified PNMT
Drugbank DB04273	8,9-Dichloro-2,3,4,5-Tetrahydro-1h-Benzo ... not specified PNMT
Drugbank DB07597	CIS-(1R,2S)-2-AMINO-1,2,3,4-TETRAHYDRONA ... not specified PNMT
Drugbank DB07739	(3R)-3-(FLUOROMETHYL)-7-(THIOMORPHOLIN-4 ... not specified PNMT
Drugbank DB07747	(3R)-N-(4-CHLOROPHENYL)-3-(HYDROXYMETHYL ... not specified PNMT
Drugbank DB07798	(3R)-3-(FLUOROMETHYL)-N-(3,3,3-TRIFLUORO ... not specified PNMT
Drugbank DB07906	[(3R)-7-NITRO-1,2,3,4-TETRAHYDROISOQUINO ... not specified PNMT
Drugbank DB08128	(1S,4R,9S)-5-(trifluoromethyl)-1,2,3,4-t ... not specified PNMT
Drugbank DB08129	(1R)-2-amino-1-[3-(trifluoromethyl)pheny ... not specified PNMT
Drugbank DB08550	7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOL ... not specified PNMT
Drugbank DB08631	N-(4-CHLOROPHENYL)-1,2,3,4-TETRAHYDROISO ... not specified PNMT
Drugbank DB08654	TRANS-(1S,2S)-2-AMINO-1,2,3,4-TETRAHYDRO ... not specified PNMT
Drugbank DB01752	S-Adenosyl-L-Homocysteine not specified PNMT
Drugbank DB03468	1,2,3,4-Tetrahydro-Isoquinoline-7-Sulfon ... not specified PNMT
Drugbank DB03824	7-Iodo-1,2,3,4-Tetrahydro-Isoquinoline not specified PNMT
Drugbank DB04273	8,9-Dichloro-2,3,4,5-Tetrahydro-1h-Benzo ... not specified PNMT

Comment	Phenylethanolamine-N-methyl transferase (PNMT) methylates norepinephrine to form epinephrine (adrenaline). (cited information)
Formal Description Interaction-ID: 74841	gene/protein PNMT increases_quantity of drug/chemical compound Adrenaline
Drugbank entries	Show/Hide entries for PNMT
Drugbank DB01752	S-Adenosyl-L-Homocysteine not specified PNMT
Drugbank DB03468	1,2,3,4-Tetrahydro-Isoquinoline-7-Sulfon ... not specified PNMT
Drugbank DB03824	7-Iodo-1,2,3,4-Tetrahydro-Isoquinoline not specified PNMT
Drugbank DB04273	8,9-Dichloro-2,3,4,5-Tetrahydro-1h-Benzo ... not specified PNMT
Drugbank DB07597	CIS-(1R,2S)-2-AMINO-1,2,3,4-TETRAHYDRONA ... not specified PNMT
Drugbank DB07739	(3R)-3-(FLUOROMETHYL)-7-(THIOMORPHOLIN-4 ... not specified PNMT
Drugbank DB07747	(3R)-N-(4-CHLOROPHENYL)-3-(HYDROXYMETHYL ... not specified PNMT
Drugbank DB07798	(3R)-3-(FLUOROMETHYL)-N-(3,3,3-TRIFLUORO ... not specified PNMT
Drugbank DB07906	[(3R)-7-NITRO-1,2,3,4-TETRAHYDROISOQUINO ... not specified PNMT
Drugbank DB08128	(1S,4R,9S)-5-(trifluoromethyl)-1,2,3,4-t ... not specified PNMT
Drugbank DB08129	(1R)-2-amino-1-[3-(trifluoromethyl)pheny ... not specified PNMT
Drugbank DB08550	7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOL ... not specified PNMT
Drugbank DB08631	N-(4-CHLOROPHENYL)-1,2,3,4-TETRAHYDROISO ... not specified PNMT
Drugbank DB08654	TRANS-(1S,2S)-2-AMINO-1,2,3,4-TETRAHYDRO ... not specified PNMT
Drugbank DB01752	S-Adenosyl-L-Homocysteine not specified PNMT
Drugbank DB03468	1,2,3,4-Tetrahydro-Isoquinoline-7-Sulfon ... not specified PNMT
Drugbank DB03824	7-Iodo-1,2,3,4-Tetrahydro-Isoquinoline not specified PNMT
Drugbank DB04273	8,9-Dichloro-2,3,4,5-Tetrahydro-1h-Benzo ... not specified PNMT

Comment	Phenylethanolamine-N-methyl transferase (PNMT) methylates norepinephrine to form epinephrine (adrenaline). (cited information)
Formal Description Interaction-ID: 74842	gene/protein PNMT decreases_quantity of drug/chemical compound Noradrenaline
Drugbank entries	Show/Hide entries for PNMT
Drugbank DB01752	S-Adenosyl-L-Homocysteine not specified PNMT
Drugbank DB03468	1,2,3,4-Tetrahydro-Isoquinoline-7-Sulfon ... not specified PNMT
Drugbank DB03824	7-Iodo-1,2,3,4-Tetrahydro-Isoquinoline not specified PNMT
Drugbank DB04273	8,9-Dichloro-2,3,4,5-Tetrahydro-1h-Benzo ... not specified PNMT
Drugbank DB07597	CIS-(1R,2S)-2-AMINO-1,2,3,4-TETRAHYDRONA ... not specified PNMT
Drugbank DB07739	(3R)-3-(FLUOROMETHYL)-7-(THIOMORPHOLIN-4 ... not specified PNMT
Drugbank DB07747	(3R)-N-(4-CHLOROPHENYL)-3-(HYDROXYMETHYL ... not specified PNMT
Drugbank DB07798	(3R)-3-(FLUOROMETHYL)-N-(3,3,3-TRIFLUORO ... not specified PNMT
Drugbank DB07906	[(3R)-7-NITRO-1,2,3,4-TETRAHYDROISOQUINO ... not specified PNMT
Drugbank DB08128	(1S,4R,9S)-5-(trifluoromethyl)-1,2,3,4-t ... not specified PNMT
Drugbank DB08129	(1R)-2-amino-1-[3-(trifluoromethyl)pheny ... not specified PNMT
Drugbank DB08550	7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOL ... not specified PNMT
Drugbank DB08631	N-(4-CHLOROPHENYL)-1,2,3,4-TETRAHYDROISO ... not specified PNMT
Drugbank DB08654	TRANS-(1S,2S)-2-AMINO-1,2,3,4-TETRAHYDRO ... not specified PNMT
Drugbank DB01752	S-Adenosyl-L-Homocysteine not specified PNMT
Drugbank DB03468	1,2,3,4-Tetrahydro-Isoquinoline-7-Sulfon ... not specified PNMT
Drugbank DB03824	7-Iodo-1,2,3,4-Tetrahydro-Isoquinoline not specified PNMT
Drugbank DB04273	8,9-Dichloro-2,3,4,5-Tetrahydro-1h-Benzo ... not specified PNMT

Comment	Patients with the depigmentation disorder vitiligo have a defect in the enzyme tyrosinase, which is the rate limiting enzyme in melanin biosynthesis from tyrosin via L-DOPA. (cited information)
Formal Description Interaction-ID: 74843	disease Vitiligo decreases_quantity of drug/chemical compound Melanin

Comment	Patients with the depigmentation disorder vitiligo have a defect in the enzyme tyrosinase, which is the rate limiting enzyme in melanin biosynthesis from tyrosine via L-DOPA. (cited information)
Formal Description Interaction-ID: 75851	disease Vitiligo decreases_activity of gene/protein TYR
Drugbank entries	Show/Hide entries for TYR
Drugbank DB00157	NADH not specified TYR
Drugbank DB00548	Azelaic Acid inhibitor TYR
Drugbank DB00600	Monobenzone inhibitor TYR
Drugbank DB01055	Mimosine inhibitor TYR
Drugbank DB00157	NADH not specified TYR
Drugbank DB01055	Mimosine inhibitor TYR

Comment	Phenylethanolamine-N-methyl transferase (PNMT) methylates norepinephrine to form epinephrine (adrenaline). (cited information)
Formal Description Interaction-ID: 76106	drug/chemical compound Noradrenaline increases_quantity of drug/chemical compound Adrenaline