Tyrosine, aromatic hydroxylation biosynthesis

Dopamine (4) serves as key intermediate in the biosynthesis of the stress hormone adrenaline (7). Two different routes are available for the biosynthesis of 4 from tyrosine (1). Hydroxylation of the aromatic ring, catalyzed by tyrosine hydroxylase, affords l-DOPA (2), which is converted to dopamine (4) via a decarboxylation step. Alternatively, tyrosine decarboxylase-mediated decarboxylation of tyrosine delivers tyramine that can be hydroxylated to afford the important bioactive intermediate 4. Hydroxylation of the benzylic position in 4 then leads to the formation of norepinephrine, also known as noradrenaline (6), which upon methylation of the amine is converted to epinephrine (adrenaline, 7) [1]. 

The aromatic amino add hydroxylases (AAHs) are a family of pterin-dependent enzymes comprising phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), and tryptophan hydroxylase (TPH, with two gene products TPH1 and TPH2). The AAHs perform the hydroxylation of aromatic amino adds and play an important role in mammalian metabolism and in the biosynthesis of... 

BA biosynthesis begins with the conversion of tyrosine to both dopamine and 4-hydroxyphenylacetaldehyde by a lattice of decarboxylations, orfho-hydroxylations, and deaminations.1 The aromatic amino acid decarboxylase (TYDC) that converts tyrosine and dopa to their corresponding amines has been purified, and several... 

Catecholamines are endogenous compounds and are synthesized in the brain, the adrenal medulla, and by some sympathetic nerve fibers. The biosynthesis of catecholamines begins with the hydroxylation of tyrosine by tyrosine hydroxylase to form L-dopa, which is decarboxylated by aromatic amino acid decarboxylase to form dopamine. Norepinephrine... 

The biosynthesis of heterocyclic and/or aromatic rings from noncyclic precursors requires complex chemical reactions. Most of these reactions (except the hydroxylation of phenylalanine to tyrosine) have been lost through evolution in animal metabolism. 

Anthramycin.—The aromatic ring of tyrosine suffers minor modification on incorporation into securinine (see above) whilst utilization in betalain biosynthesis results in ring cleavage between C-3 and C-4 after hydroxylation to dopa (see below). Similar degradation of tyrosine occurs in the biosynthesis of anthramycin (166), an antibiotic produced by Streptomyces refuineus. var thermotolerans. ... 

Phenylalanine hydroxylase [39] catalyzes the first step of phenylalanine degradation in mammals. Phenylalanine is converted into tyrosine (Scheme XI.9). The enzyme has one tightly bound, non-heme iron atom per subunit. Tyrosine hydroxylase catalyzes [40] the hydroxylation of tyrosine to produce dihydroxy-phenylalanine (DOPA), the first step in the biosynthesis of catechol-amine neurotransmitters (Scheme XI.9). This enzyme also contains one ferrous iron atom per subunit. These two enzymes, together with tryptophane hydroxylase (Scheme XI.9) [41], constitute a family of tetrahydropterin-dependent aromatic acid hydroxylases (monooxygenases) [42], Other dioxygenases catalyze the hydroxylation ofarenes [43],... 

The biosynthesis of benzyltetrahydroisoquinoline alkaloids has been thoroughly studied—mainly because of the medicinal and commercial importance of opium alkaloids— and commences with the preparation of (5)-reticuline (19). Reticuline then presents a point of divergence and as starting point for the biosynthesis of the previously named tyrosine-derived alkaloids with different skeletal structures [14-16]. The route to (5)-reticuline is outlined in Scheme 12.3. Both reaction partners for the condensation reaction and formation of (S)-norcoclaurine (16) are derived from tyrosine. The aromatic portions in (S)-reticuline (19) possess an ortho-dihydroxylation pattern as present in dopamine (4). However, only the northern portion in 19 is derived from dopamine, and the second hydroxyl functionality in the southern part is introduced after the formation of the tetrahydroisoquinoline ring system. The synthesis of the southern portion in... 

Phosphorylation of 3-hydroxyl group of shikimate by shikimate kinase (EC 2.7.1.71) with ATP as a cosubstrate initiates the biosynthesis pathway of anthranilic acid [2], This step also presents the first step of the shikimate pathway, which is a metabolic route used by bacteria, fungi, and plants for the biosynthesis of many aromatic products such as lignins, alkaloids, flavonoids, benzoic acid, and plant hormones, in addition to the aromatic amino acids (phenylalaiune, tyrosine, and tryptophan). The sequential EPSP synthesis is catalyzed by EPSP synthase (EC 2.5.1.19) through the addition of phosphoenolpyruvate to 3-phospho-shikimate followed elimination of phosphate. EPSP synthase belongs to the family of transferases, specifically to those transferring aryl... 

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