Department of Biological Sciences, St. Mary's University, San Antonio, TX 78228, USA.
Arch Biochem Biophys. 2011 Apr 1;508(1):1-12. doi: 10.1016/j.abb.2010.12.017. Epub 2010 Dec 19.
Tyrosine hydroxylase is the rate-limiting enzyme of catecholamine biosynthesis; it uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to DOPA. Its amino terminal 150 amino acids comprise a domain whose structure is involved in regulating the enzyme's activity. Modes of regulation include phosphorylation by multiple kinases at four different serine residues, and dephosphorylation by two phosphatases. The enzyme is inhibited in feedback fashion by the catecholamine neurotransmitters. Dopamine binds to TyrH competitively with tetrahydrobiopterin, and interacts with the R domain. TyrH activity is modulated by protein-protein interactions with enzymes in the same pathway or the tetrahydrobiopterin pathway, structural proteins considered to be chaperones that mediate the neuron's oxidative state, and the protein that transfers dopamine into secretory vesicles. TyrH is modified in the presence of NO, resulting in nitration of tyrosine residues and the glutathionylation of cysteine residues.
酪氨酸羟化酶是儿茶酚胺生物合成的限速酶；它使用四氢生物蝶呤和分子氧将酪氨酸转化为多巴。其氨基末端 150 个氨基酸组成一个结构域，该结构域参与调节酶的活性。调节方式包括四种不同丝氨酸残基的多个激酶的磷酸化，以及两种磷酸酶的去磷酸化。该酶被儿茶酚胺神经递质以反馈方式抑制。多巴胺与四氢生物蝶呤竞争结合 TyrH，并与 R 结构域相互作用。TyrH 活性受到与同一途径或四氢生物蝶呤途径中的酶的蛋白-蛋白相互作用、被认为介导神经元氧化状态的结构蛋白以及将多巴胺转移到分泌小泡中的蛋白的调节。在存在 NO 的情况下，TyrH 会发生修饰，导致酪氨酸残基的硝化和半胱氨酸残基的谷胱甘肽化。
