Metabolism of amine-derived hormones (Homo sapiens)
From WikiPathways
Description
Catecholamines and thyroxine are synthesized from tyrosine, and serotonin and melatonin from tryptophan.
View original pathway at:Reactome.
Quality Tags
Ontology Terms
Bibliography
View all... |
- Rodriguez IR, Mazuruk K, Schoen TJ, Chader GJ.; ''Structural analysis of the human hydroxyindole-O-methyltransferase gene. Presence of two distinct promoters.''; PubMed Europe PMC Scholia
- Kobayashi K, Morita S, Mizuguchi T, Sawada H, Yamada K, Nagatsu I, Fujita K, Nagatsu T.; ''Functional and high level expression of human dopamine beta-hydroxylase in transgenic mice.''; PubMed Europe PMC Scholia
- Walther DJ, Peter JU, Bashammakh S, Hörtnagl H, Voits M, Fink H, Bader M.; ''Synthesis of serotonin by a second tryptophan hydroxylase isoform.''; PubMed Europe PMC Scholia
- Salvatore D, Low SC, Berry M, Maia AL, Harney JW, Croteau W, St Germain DL, Larsen PR.; ''Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme.''; PubMed Europe PMC Scholia
- Gnidehou S, Lacroix L, Sezan A, Ohayon R, Noël-Hudson MS, Morand S, Francon J, Courtin F, Virion A, Dupuy C.; ''Cloning and characterization of a novel isoform of iodotyrosine dehalogenase 1 (DEHAL1) DEHAL1C from human thyroid: comparisons with DEHAL1 and DEHAL1B.''; PubMed Europe PMC Scholia
- Degroot LJ, Niepomniszcze H.; ''Biosynthesis of thyroid hormone: basic and clinical aspects.''; PubMed Europe PMC Scholia
- Lagorce JF, Thomes JC, Catanzano G, Buxeraud J, Raby M, Raby C.; ''Formation of molecular iodine during oxidation of iodide by the peroxidase/H2O2 system. Implications for antithyroid therapy.''; PubMed Europe PMC Scholia
- Lewis DA, Melchitzky DS, Haycock JW.; ''Four isoforms of tyrosine hydroxylase are expressed in human brain.''; PubMed Europe PMC Scholia
- Flatmark T.; ''Catecholamine biosynthesis and physiological regulation in neuroendocrine cells.''; PubMed Europe PMC Scholia
- Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA.; ''Tryptophan metabolism in the central nervous system: medical implications.''; PubMed Europe PMC Scholia
- Ichinose H, Kurosawa Y, Titani K, Fujita K, Nagatsu T.; ''Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase.''; PubMed Europe PMC Scholia
- Coon SL, Mazuruk K, Bernard M, Roseboom PH, Klein DC, Rodriguez IR.; ''The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT): structure, chromosomal localization, and tissue expression.''; PubMed Europe PMC Scholia
- Smanik PA, Liu Q, Furminger TL, Ryu K, Xing S, Mazzaferri EL, Jhiang SM.; ''Cloning of the human sodium lodide symporter.''; PubMed Europe PMC Scholia
- Kaneda N, Ichinose H, Kobayashi K, Oka K, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T.; ''Molecular cloning of cDNA and chromosomal assignment of the gene for human phenylethanolamine N-methyltransferase, the enzyme for epinephrine biosynthesis.''; PubMed Europe PMC Scholia
- Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC.; ''Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin.''; PubMed Europe PMC Scholia
- Ishii A, Kobayashi K, Kiuchi K, Nagatsu T.; ''Expression of two forms of human dopamine-beta-hydroxylase in COS cells.''; PubMed Europe PMC Scholia
- Ameziane-El-Hassani R, Morand S, Boucher JL, Frapart YM, Apostolou D, Agnandji D, Gnidehou S, Ohayon R, Noël-Hudson MS, Francon J, Lalaoui K, Virion A, Dupuy C.; ''Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity.''; PubMed Europe PMC Scholia
- Sumi-Ichinose C, Ichinose H, Takahashi E, Hori T, Nagatsu T.; ''Molecular cloning of genomic DNA and chromosomal assignment of the gene for human aromatic L-amino acid decarboxylase, the enzyme for catecholamine and serotonin biosynthesis.''; PubMed Europe PMC Scholia
- Lamouroux A, Vigny A, Faucon Biguet N, Darmon MC, Franck R, Henry JP, Mallet J.; ''The primary structure of human dopamine-beta-hydroxylase: insights into the relationship between the soluble and the membrane-bound forms of the enzyme.''; PubMed Europe PMC Scholia
- Glatt CE, Wahner AD, White DJ, Ruiz-Linares A, Ritz B.; ''Gain-of-function haplotypes in the vesicular monoamine transporter promoter are protective for Parkinson disease in women.''; PubMed Europe PMC Scholia
- Edens WA, Sharling L, Cheng G, Shapira R, Kinkade JM, Lee T, Edens HA, Tang X, Sullards C, Flaherty DB, Benian GM, Lambeth JD.; ''Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox.''; PubMed Europe PMC Scholia
- Cleary S, Brouwers FM, Eisenhofer G, Pacak K, Christie DL, Lipski J, McNeil AR, Phillips JK.; ''Expression of the noradrenaline transporter and phenylethanolamine N-methyltransferase in normal human adrenal gland and phaeochromocytoma.''; PubMed Europe PMC Scholia
- Mandel SJ, Berry MJ, Kieffer JD, Harney JW, Warne RL, Larsen PR.; ''Cloning and in vitro expression of the human selenoprotein, type I iodothyronine deiodinase.''; PubMed Europe PMC Scholia
- Köhrle J, Brabant G, Hesch RD.; ''Metabolism of the thyroid hormones.''; PubMed Europe PMC Scholia
History
View all... |
External references
DataNodes
View all... |
Annotated Interactions
View all... |
Source | Target | Type | Database reference | Comment |
---|---|---|---|---|
4aOH-BH4 | Arrow | R-HSA-209823 (Reactome) | ||
4aOH-BH4 | Arrow | R-HSA-209828 (Reactome) | ||
5HT | Arrow | R-HSA-209859 (Reactome) | ||
5HTP | Arrow | R-HSA-209828 (Reactome) | ||
5HTP | R-HSA-209859 (Reactome) | |||
5HT | R-HSA-209792 (Reactome) | |||
AANAT | mim-catalysis | R-HSA-209792 (Reactome) | ||
ADR | Arrow | R-HSA-209903 (Reactome) | ||
ASMT | mim-catalysis | R-HSA-209821 (Reactome) | ||
Ac-CoA | R-HSA-209792 (Reactome) | |||
Ac5HT | Arrow | R-HSA-209792 (Reactome) | ||
Ac5HT | R-HSA-209821 (Reactome) | |||
AdoHcy | Arrow | R-HSA-209821 (Reactome) | ||
AdoHcy | Arrow | R-HSA-209903 (Reactome) | ||
AdoMet | R-HSA-209821 (Reactome) | |||
AdoMet | R-HSA-209903 (Reactome) | |||
BH4 | R-HSA-209823 (Reactome) | |||
BH4 | R-HSA-209828 (Reactome) | |||
CO2 | Arrow | R-HSA-209859 (Reactome) | ||
CO2 | Arrow | R-HSA-209924 (Reactome) | ||
CoA-SH | Arrow | R-HSA-209792 (Reactome) | ||
DA | Arrow | R-HSA-209924 (Reactome) | ||
DA | Arrow | R-HSA-351596 (Reactome) | ||
DA | R-HSA-209891 (Reactome) | |||
DA | R-HSA-351596 (Reactome) | |||
DBH tetramer | mim-catalysis | R-HSA-209891 (Reactome) | ||
DDC dimer | mim-catalysis | R-HSA-209859 (Reactome) | ||
DDC dimer | mim-catalysis | R-HSA-209924 (Reactome) | ||
DEHAL1:FMN | mim-catalysis | R-HSA-209921 (Reactome) | ||
DEHAL1:FMN | mim-catalysis | R-HSA-209960 (Reactome) | ||
DHvitC | Arrow | R-HSA-209891 (Reactome) | ||
DIO dimer | mim-catalysis | R-HSA-209772 (Reactome) | ||
DIO3 | mim-catalysis | R-HSA-350869 (Reactome) | ||
DIT | Arrow | R-HSA-209973 (Reactome) | ||
DIT | R-HSA-209840 (Reactome) | |||
DIT | R-HSA-209925 (Reactome) | |||
DIT | R-HSA-209960 (Reactome) | |||
DUOX1,2 | mim-catalysis | R-HSA-5693681 (Reactome) | ||
H+ | Arrow | R-HSA-209821 (Reactome) | ||
H+ | Arrow | R-HSA-209903 (Reactome) | ||
H+ | R-HSA-209772 (Reactome) | |||
H+ | R-HSA-209973 (Reactome) | |||
H+ | R-HSA-350869 (Reactome) | |||
H+ | R-HSA-350901 (Reactome) | |||
H+ | R-HSA-5693681 (Reactome) | |||
H2O2 | Arrow | R-HSA-5693681 (Reactome) | ||
H2O2 | R-HSA-209973 (Reactome) | |||
H2O2 | R-HSA-350901 (Reactome) | |||
H2O | Arrow | R-HSA-209891 (Reactome) | ||
H2O | Arrow | R-HSA-209973 (Reactome) | ||
H2O | Arrow | R-HSA-350901 (Reactome) | ||
HI | Arrow | R-HSA-209815 (Reactome) | ||
I- | Arrow | R-HSA-209772 (Reactome) | ||
I- | Arrow | R-HSA-209910 (Reactome) | ||
I- | Arrow | R-HSA-209921 (Reactome) | ||
I- | Arrow | R-HSA-209960 (Reactome) | ||
I- | Arrow | R-HSA-350869 (Reactome) | ||
I- | R-HSA-209910 (Reactome) | |||
I- | R-HSA-209973 (Reactome) | |||
I- | R-HSA-350901 (Reactome) | |||
I2 | Arrow | R-HSA-350901 (Reactome) | ||
I2 | R-HSA-209815 (Reactome) | |||
L-Ala | Arrow | R-HSA-209840 (Reactome) | ||
L-Ala | Arrow | R-HSA-209925 (Reactome) | ||
L-Dopa | Arrow | R-HSA-209823 (Reactome) | ||
L-Dopa | R-HSA-209924 (Reactome) | |||
L-Trp | R-HSA-209828 (Reactome) | |||
L-Tyr | Arrow | R-HSA-209921 (Reactome) | ||
L-Tyr | Arrow | R-HSA-209960 (Reactome) | ||
L-Tyr | R-HSA-209815 (Reactome) | |||
L-Tyr | R-HSA-209823 (Reactome) | |||
L-Tyr | R-HSA-209973 (Reactome) | |||
MIT | Arrow | R-HSA-209815 (Reactome) | ||
MIT | R-HSA-209921 (Reactome) | |||
MIT | R-HSA-209925 (Reactome) | |||
MLT | Arrow | R-HSA-209821 (Reactome) | ||
NADP+ | Arrow | R-HSA-209772 (Reactome) | ||
NADP+ | Arrow | R-HSA-209921 (Reactome) | ||
NADP+ | Arrow | R-HSA-209960 (Reactome) | ||
NADP+ | Arrow | R-HSA-209973 (Reactome) | ||
NADP+ | Arrow | R-HSA-350869 (Reactome) | ||
NADP+ | Arrow | R-HSA-350901 (Reactome) | ||
NADP+ | Arrow | R-HSA-5693681 (Reactome) | ||
NADPH | R-HSA-209772 (Reactome) | |||
NADPH | R-HSA-209921 (Reactome) | |||
NADPH | R-HSA-209960 (Reactome) | |||
NADPH | R-HSA-209973 (Reactome) | |||
NADPH | R-HSA-350869 (Reactome) | |||
NADPH | R-HSA-350901 (Reactome) | |||
NADPH | R-HSA-5693681 (Reactome) | |||
NAd | Arrow | R-HSA-209891 (Reactome) | ||
NAd | Arrow | R-HSA-351604 (Reactome) | ||
NAd | R-HSA-209903 (Reactome) | |||
NAd | R-HSA-351604 (Reactome) | |||
Na+ | Arrow | R-HSA-209910 (Reactome) | ||
Na+ | R-HSA-209910 (Reactome) | |||
O2 | R-HSA-209823 (Reactome) | |||
O2 | R-HSA-209828 (Reactome) | |||
O2 | R-HSA-209891 (Reactome) | |||
O2 | R-HSA-5693681 (Reactome) | |||
PNMT | mim-catalysis | R-HSA-209903 (Reactome) | ||
R-HSA-209772 (Reactome) | Iodothyronine deiodinases 1 and 2 (DIO1/2) are the vertebrate enzymes responsible for the deiodination of the prohormone thyroxine (T4; 3,5,3',5'-tetraiodothyronine) into the biologically active hormone T3 (3,5,3'-triiodothyronine). DIO1/2 activity is critical for appropriate T3 levels in the brain during development. | |||
R-HSA-209792 (Reactome) | Serotonin N-acetyltransferase (AANAT) catalyzes the N-acetylation of serotonin to form N-acetylserotonin. AANAT utilizes acetyl-CoA as the donor of the acetyl group. | |||
R-HSA-209815 (Reactome) | Tyrosines can be iodinated in thyroglobulin to produce precursors for thyroid hormone synthesis. | |||
R-HSA-209821 (Reactome) | Hydroxyindole-O-methyltransferase (HIOMT) catalyzes the last step in the synthesis of melatonin. Melatonin is synthesized and released by the pineal gland and is thought to control circadian rhythms. HIOMT has 3 isoforms and utilizes S-adenosyl-L-methionine (SAM) as the methyl donor in the conversion of N-acetyl-5HT to melatonin. | |||
R-HSA-209823 (Reactome) | Tyrosine hydroxylase (TH) is the first enzyme in catecholamine biosynthesis, as well as being the rate-limiting enzyme in that process. TH requires tetrahydrobiopterin and uses iron as a cofactor in the 3,4-hydroxylation of tyrosine to produce dopa. Four isoforms of TH are expressed in the human brain and all have enzymatic activity (Nagatsu, T, 1989; Lewis, DA et al, 1993). | |||
R-HSA-209828 (Reactome) | The first and rate limiting step in serotonin (5-HT) biosynthesis is catalyzed by tryptophan hydroxylase. The enzyme requires iron(II), tetrahydrobiopterin, and dioxygen cofactors for the hydroxylation of L-tryptophan to 5-hydroxytryptophan. Tryptophan hydroxylase belongs to a small family of monooxygenases that utilize tetrahydrobiopterins. Other members are phenylalanine hydroxylase and tyrosine hydroxylase (Fitzpatrick, PF, 1999; Walther et al, 2003). | |||
R-HSA-209840 (Reactome) | Thyroxine (T4) can be formed by the combination of two diiodotyrosines. The hormone thyrotropin can stimulate the production of T3 and T4. | |||
R-HSA-209859 (Reactome) | Aromatic L-amino acid decarboxylase (AADC) catalyzes the decarboxylation of both dopa and 5-hydroxytryptophan to dopamine and serotonin, respectively. AADC functions as a homodimer, utilizing pyridoxal phosphate as a cofactor. | |||
R-HSA-209891 (Reactome) | Dopamine beta-hydroxylase (DBH; dopamine beta-monooxygenase) is a copper-containing glycoprotein consisting of four identical subunits and catalyzes the oxidation of dopamine to norepinephrine. It requires ascorbic acid as an electron donor. DBH is localized in the norepinephrinergic and epinephrinergic neurons in the central nervous system. The enzyme exists in the secretory vesicles as both soluble and membrane-bound forms. The soluble form is secreted with catecholamines by exocytosis whereas the membrane-bound form is recycled into the vesicles. | |||
R-HSA-209903 (Reactome) | Phenylethanolamine N-methyltransferase (PNMT) is the terminal enzyme in catecholamine biosynthesis. It performs transmethylation of noradrenaline to adrenaline using S-adenosyl L-methionine (SAM) as the methyl donor. | |||
R-HSA-209910 (Reactome) | Iodide (I-) is transported from blood serum into the thyroid cell by the Na+/I- symporter (sodium/iodide). This intrinsic membrane protein uses energy from the inward movement of Na+ to drive the process and accumulate I- in the cell, maintaining a cellular concentration 30-40 times that of the serum concentration. This process, also called the iodide trap, is stimulated by TSH (thyroid stimulating hormone) and is saturable by large amounts of I-. | |||
R-HSA-209921 (Reactome) | The human iodotyrosine dehalogenase 1 (DEHAL1) gene is composed of six exons. Two isoforms (DEHAL1 and DEHAL1B) have been published, both of which have a nitroreductase domain and arise from differential splicing in exon 5. The DEHAL1 isoform is a transmembrane protein that catalyzes the NADPH-dependent deiodination of monoiodotyrosine (MIT) and diiodotyrosine (DIT). | |||
R-HSA-209924 (Reactome) | Aromatic L-amino acid decarboxylase (AADC, dopa decarboxylase) decarboxylates dopa to form dopamine. | |||
R-HSA-209925 (Reactome) | Mono- and di-iodinated tyrosine can combine to form tri-iodothyronine (T3). The hormone thyrotropin can stimulate the production of T3 and T4. | |||
R-HSA-209960 (Reactome) | The human iodotyrosine dehalogenase 1 (DEHAL1) gene is composed of six exons. Two isoforms (DEHAL1 and DEHAL1B) have been published, both of which have a nitroreductase domain and arise from differential splicing in exon 5. The DEHAL1 isoform is a transmembrane protein that catalyzes the NADPH-dependent deiodination of monoiodotyrosine (MIT) and diiodotyrosine (DIT). | |||
R-HSA-209973 (Reactome) | Tyrosines can be iodinated in thyroglobulin to produce precursors for thyroid hormone synthesis. | |||
R-HSA-350869 (Reactome) | Type III iodothyronine deiodinase (DIO3) is an integral membrane protein (Baqui M et al, 2003) and catalyzes the conversion of T4 (3,5,3',5'-tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and T3 (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine). Both RT3 and T2 are inactive metabolites. It is thought DIO3 plays an essential role for regulation of thyroid hormone inactivation during embryological development. | |||
R-HSA-350901 (Reactome) | The first step in the biogenesis of thyroid hormones is the oxidation of iodide (I-) by H2O2/peroxidase after being taken up by the thyroid gland. This event is known as organification. | |||
R-HSA-351596 (Reactome) | While dopamine is synthesized in the cytosol, its conversion to noradrenaline is mediated by a vesicle-associated enzyme. The process by which dopamine is transported across the vesicle membrane has not been elucidated yet, however. | |||
R-HSA-351604 (Reactome) | While noradrenaline is synthesized in the secretory vesicle, its conversion to adrenaline is mediated by a cytosolic enzyme. The process by which noradrenaline is transported across the vesicle membrane has not been worked out, however. | |||
R-HSA-5693681 (Reactome) | Dual oxidases 1 and 2 (DUOX1, 2) mediates the generation of hydrogen peroxide (H2O2) which is required for the activity of thyroid peroxidase for thyroid hormone formation and lactoperoxidase (Edens et al. 2001, Ameziane-El-Hassani et al. 2005). | |||
SLC5A5 | mim-catalysis | R-HSA-209910 (Reactome) | ||
T3 | Arrow | R-HSA-209772 (Reactome) | ||
T3 | Arrow | R-HSA-209925 (Reactome) | ||
T3 | Arrow | R-HSA-350869 (Reactome) | ||
T4 | Arrow | R-HSA-209840 (Reactome) | ||
T4 | R-HSA-209772 (Reactome) | |||
T4 | R-HSA-350869 (Reactome) | |||
TH:Fe2+ | mim-catalysis | R-HSA-209823 (Reactome) | ||
TPH:Fe++ | mim-catalysis | R-HSA-209828 (Reactome) | ||
TPO | mim-catalysis | R-HSA-209815 (Reactome) | ||
TPO | mim-catalysis | R-HSA-209840 (Reactome) | ||
TPO | mim-catalysis | R-HSA-209925 (Reactome) | ||
TPO | mim-catalysis | R-HSA-209973 (Reactome) | ||
TPO | mim-catalysis | R-HSA-350901 (Reactome) | ||
Thyrotropin | Arrow | R-HSA-209840 (Reactome) | ||
Thyrotropin | Arrow | R-HSA-209925 (Reactome) | ||
VitC | R-HSA-209891 (Reactome) |