SYNTHESIS AND RELEASE OF BIOGENIC AMINES

在儿茶酚胺生物合成的限速步骤中，酪氨酸羟基酶(TH)催化酪氨酸羟化为二氢苯丙氨酸。该反应需要将分子氧还原为水，并将氧原子结合到酪氨酸的芳香环中。TH的活性依赖于四氢生物蝶呤和非血红素铁。苯丙氨酸羟基酶(PAH)和TH系统的最新证据表明，氢过氧四氢生物蝶呤是羟化物种。铁的作用尚不清楚；然而，在无铁的TH中缺乏活性与铁在催化中具有重要作用是一致的。铁被认为是促进过氧基中间体的形成，但不排除铁氧基中间体作为羟化物种的可能性。目前的研究主要集中在TH反应的羟化物种的鉴定以及反应物的化学计量和结合顺序。通过用氧电极在密封室中监测反应，获得了初步结果。在空气饱和的缓冲液中，在没有酪氨酸的情况下，每摩尔的TH活性中心消耗一摩尔的分子氧。这种摄氧量似乎依赖于四氢生物蝶呤而不是酪氨酸，这表明羟化物种的氧依赖形成可能与酪氨酸依赖的羟化分开。进一步的研究正在进行中，以证实这些结果，并将氧活化从羟化步骤分离到单独的好氧和厌氧反应中。-酪氨酸羟基酶，儿茶酚胺，二氢苯丙氨酸，四氢生物蝶呤，中间体

Tyrosine hydroxylase (TH) catalyzes the hydroxylation of tyrosine to dihydrophenylalanine in the rate limiting step of catecholamine biosynthesis. The reaction requires the reduction of molecular oxygen to water with an oxygen atom incorporated into the aromatic ring of tyrosine. TH is dependent on tetrahydrobiopterin as well as a non-heme iron for activity. Current evidence for both the phenylalanine hydroxylase (PAH) and TH systems suggests that a hydroperoxytetrahydrobiopterin is the hydroxylating species. The role of the iron is unclear; however, the lack of activity in iron-free TH is consistent with the Fe having an essential role in catalysis. The Fe is proposed to facilitate the formation of the peroxy intermediate while an Fe oxo intermediate as the hydroxylating species has not been ruled out. Present studies are focused on the identification of the hydroxylating species of the TH reaction and the stoichiometry and order of binding of the reactants. Preliminary results have been obtained by monitoring the reaction in a sealed chamber with an oxygen electrode. In air-saturated buffer one mole of molecular oxygen is consumed for each mole of TH active sites in the absence of tyrosine. This oxygen uptake appears to be dependent on tetrahydrobiopterin and not tyrosine, evidence that the oxygen dependent formation of the hydroxylating species may be separate from the tyrosine dependent hydroxylation. Further studies are underway to confirm these results as well as to isolate the oxygen activation from the hydroxylation steps into separate aerobic and anaerobic reactions. - tyrosine hydroxylase, catecholamine, dihydrophenylalanine, tetrahydrobiopterin, intermediate