Tyrosine hydroxylase and regulation of dopamine synthesis.

  title={Tyrosine hydroxylase and regulation of dopamine synthesis.},
  author={Susan Colette Daubner and Tiffany Le and Shanzhi Wang},
  journal={Archives of biochemistry and biophysics},
  volume={508 1},
Complex molecular regulation of tyrosine hydroxylase
The myriad mechanisms that regulate tyrosine hydroxylase expression and activity are revisited and their physiological importance in the control of catecholamine biosynthesis is highlighted.
Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation
The authors present the cryo-EM structures of full-length human TH in the apo form and bound with DA, as well as the structure of Ser40 phosphorylated TH, and discuss the inhibitory and stabilizing effects of DA on TH and its counteraction by Ser40-phosphorylation.
The solution structure of the regulatory domain of tyrosine hydroxylase.
Tyrosine hydroxylase phosphorylation in vivo
This review on TH phosphorylation in vivo has three main sections focusing on: the methods used to investigate TH phosphate levels in vivo, the animals used, the sacrifice procedures, the tissue preparation, the measurement of TH protein levels and THosphorylation and the measurements of TH activation.
Novel enhancement mechanism of tyrosine hydroxylase enzymatic activity by nitric oxide through S-nitrosylation
The results provide a novel mechanism of how NO can modulate TH’s enzymatic activity through S-nitrosylation, which is a reversible modification of cysteine residue in protein and is known to be an emerging signaling mechanism mediated by NO.
Zinc antagonizes iron-regulation of tyrosine hydroxylase activity and dopamine production in Drosophila melanogaster
Catsup, the Drosophila ortholog of the mammalian zinc transporter SLC39A7 (ZIP7), is found to be a functional zinc transporter that regulates intracellular zinc distribution between the ER/Golgi and the cytosol, uncovered a previously unknown mechanism underlying the control of cellular dopamine expression.
The Monomeric Species of the Regulatory Domain of Tyrosine Hydroxylase Has a Low Conformational Stability.
Both RD species were disordered below physiological pH, but the acquisition of secondary native-like structure occurs at pHs lower than those measured for the attainment of tertiary native- and compactness-like arrangements.
Subcellular distribution of human tyrosine hydroxylase isoforms 1 and 4 in SH‐SY5Y cells
This is the first study to show a difference in subcellular distribution between two human TH isoforms under basal and stimulated conditions.


Role of N-terminus of tyrosine hydroxylase in the biosynthesis of catecholamines
Investigation of the role of the N-terminus of TH enzyme in the regulation of both the catalytic activity and the intracellular stability will extend the spectrum of the gene-therapy approach for PD.
Effects of phosphorylation on binding of catecholamines to tyrosine hydroxylase: specificity and thermodynamics.
A structural model for the effect of phosphorylation is proposed and the results show that in the case of binding of dihydroxyphenylalanine, the decrease in affinity upon phosphorylations is due primarily to a decrease in the enthalpy of the interaction.
Effects of substitution at serine 40 of tyrosine hydroxylase on catecholamine binding.
The results suggest that the serine hydroxyl contributes to the stabilization of the catecholamine-inhibited enzyme, and the S40E enzyme will be useful in further studies of the effects of multiple phosphorylation on tyrosines, while the alanine enzyme does not provide an accurate mimic of the unphosphorylated enzyme.
Effects of phosphorylation by protein kinase A on binding of catecholamines to the human tyrosine hydroxylase isoforms
The results extend the regulatory model developed for the rat enzyme, in which the activity of hTyrH is regulated by the opposing effects of catecholamine binding and phosphorylation by PKA.
Mutation of regulatory serines of rat tyrosine hydroxylase to glutamate: effects on enzyme stability and activity.
Effects of phosphorylation of serine 40 of tyrosine hydroxylase on binding of catecholamines: evidence for a novel regulatory mechanism.
The results support a novel mechanism for regulation in which phosphorylation affects binding of catecholamines to the catalytically inactive ferric form of the tyrosine hydroxylase.
Direct Binding of GTP Cyclohydrolase and Tyrosine Hydroxylase
The physical association of tyrosine hydroxylase and GTP cyclohydrolase is confirmed, identifying interacting regions in both, and it is demonstrated that their association can be regulated by phosphorylation, demonstrating that these enzymes engage in mutual positive regulation.
The aromatic amino acid hydroxylases.
  • P. Fitzpatrick
  • Biology, Chemistry
    Advances in enzymology and related areas of molecular biology
  • 2000
While the complex regulatory properties of phenylalanine and tyrosine hydroxylase are still not fully understood, effects of regulation on key kinetic parameters have been identified and the ligands to the active site iron atom as well as residues involved in substrate binding have be identified.
Tyrosine hydroxylase activity is regulated by two distinct dopamine‐binding sites
Tyrosine hydroxylase (TH), the rate‐limiting enzyme in the biosynthesis of the catecholamines dopamine, noradrenaline and adrenaline, is regulated acutely by feedback inhibition by the catecholamines
Reduced nicotinamide nucleotides prevent nitration of tyrosine hydroxylase by peroxynitrite