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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.
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.
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.
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).
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).
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.
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.
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.
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-.
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).
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).
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.
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.
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.
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.
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).
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