Where is tyrosine hydroxylase located

A reduction in normal tyrosine hydroxylase enzyme leads to a decrease in the production of dopamine, which causes the movement problems characteristic of dopa-responsive dystonia. The amount of functional enzyme that is produced is associated with the severity of the signs and symptoms.

Less functional enzyme leads to more severe symptoms. More than 20 mutations in the TH gene have been identified in people with tyrosine hydroxylase TH deficiency.

These mutations result in reduced activity of the tyrosine hydroxylase enzyme. As a result, the body produces less dopamine, norepinephrine, and epinephrine. These catecholamines are necessary for normal nervous system function, and changes in their levels contribute to the abnormal movements, nervous system dysfunction, and other neurological problems seen in people with TH deficiency.

Dopa-responsive dystonia is sometimes considered a mild form of tyrosine hydroxylase deficiency. It is uncertain whether they are two separate disorders or part of the same disease spectrum. Certain common TH variations polymorphisms modify catecholamine production, which affects the risk of developing conditions associated with regulation of the autonomic nervous system.

These TH gene polymorphisms affect the extent to which blood pressure increases with stress and may increase the risk of high blood pressure hypertension. SIDS is a major cause of death in babies younger than 1 year.

It is characterized by sudden and unexplained death, usually during sleep. This version of the gene may affect the regulation of breathing or awakening in infants. Genetics Home Reference has merged with MedlinePlus.

Learn more. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health. TH gene tyrosine hydroxylase. From Genetics Home Reference. Trends Neurosci.

Kaufman, S. Studies on the mechanism of the enzymatic conversion of phenylalanine to tyrosine. Smyth, C. Further tests for linkage of bipolar affective disorder to the tyrosine hydroxylase gene locus on chromosome 11p15 in a new series of multiplex British affective disorder pedigrees. CAS Google Scholar. Thibaut, F. Association of DNA polymorphism in the first intron of the tyrosine hydroxylase gene with disturbances of the catecholaminergic system in schizophrenia. Schizophrenia Res. Ludecke, B.

Google Scholar. A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome. Fitzpatrick, P. Steady-state kinetic mechanism of rat tyrosine hydroxylase. Biochemistry 30 , — Kinetic isotope effects on hydroxylation of ring-deuterated phenylalanines by tyrosine hydroyxlase provide evidence against partitioning of an arene oxide intermediate. Hillas, P. A mechanism for hydroxylation by tyrosine hydroxylase based on partitioning of substituted phenylalanines.

Biochemistry 35 , — Hufton, S. Structure and function of the aromatic amino acid hydroxylases. Studies of the rate-limiting step in the tyrosine hydroxylase reaction: alternate substrates, solvent isotope effects, and transition-state analogues. Daubner, S. Expression and characterization of the catalytic and regulatory domains of rat tyrosine hydroxylase.

Rost, B. PHD: Predicting one-dimensional protein structure by profile-based neural networks. Dickson, P. Delineation of the catalytic core of phenylalanine hydroxylase and identification of glutamate as a critical residue for pterin function.

Vrana, K. A carboxyl terminal leucine zipper is required for tyrosine hydroxylase tetramer formation. Lohse, D. Identification of the intersubunit binding region in rat tyrosine hydroxylase. Lupas, A. Coiled coils: new structures and new functions. Trends Biochem. Bennett, M. Quinsey, N. Identification of Gln and Pro as residues critical for substrate inhibition in tyrosine hydroxylase. Protein Sci. Nucleic Adds Res. Iwaki, M. Proteolytic modification of the amino-terminal and carboxyl-terminal regions of rat hepatic phenylalanine hydroxylase.

Ramsey, A. Identification of iron ligands in tyrosine hydroxylase by mutagenesis of conserved histidine residues. Meyerklaucke, W. Mossbauer, electron-paramagnetic-resonance and X-ray absorption fine-structure studies of the iron environment in recombinant tyrosine hydroxylase. Characterization of the active site iron in tyrosine hydroxylase — redox states of the iron. As the size of the substituent at the 4-position increased, the site of hydroxylation switched from the 4- to the 3-position of the aromatic ring.

These values are consistent with a highly electron deficient transition state for hydroxylation. Oxygen addition at the 4-position resulted in either elimination of the substituent to form tyrosine or an NIH shift to form the respective 3-X-tyrosine. A chemical mechanism for hydroxylation by tyrosine hydroxylase is presented to account for product formation from the various 4-substituted phenylalanines. Welch Foundation Grant A Address correspondence to Paul F.

Syntheses and characterization of the amino acids used in this study 7 pages. Ordering information is given on any current masthead page.

Such files may be downloaded by article for research use if there is a public use license linked to the relevant article, that license may permit other uses. View Author Information. Cite this: Biochemistry , 35 , 22 , — Article Views Altmetric -. Citations Abstract The iron-containing enzyme tyrosine hydroxylase catalyzes the hydroxylation of tyrosine to dihydroxyphenylalanine. Supporting Information Available. Cited By. This article is cited by 60 publications.

Edward I. Solomon, Dory E. DeWeese, Jeffrey T. Babicz, Jr. Journal of the American Chemical Society , 12 , Subedi, Paul F. Journal of the American Chemical Society , 15 , Subedi and Paul F. Biochemistry , 55 49 , Krzyaniak , Bekir E. Eser , Holly R. Ellis , Paul F. Fitzpatrick , and John McCracken. Biochemistry , 52 47 , Shah , John A. Conrad , and Graham R. Biochemistry , 52 35 , Bailey , Dimitrios Barrera , Jaclyn Y.

Bermudez , David H. Giles , Crystal A. Oxley , and Paul F. Biochemistry , 52 8 , Biochemistry , 52 6 , Conrad , Brian Heinz , June M.

Brownlee , and Graham R. Biochemistry , 50 35 , Martin Bollinger, Jr. Biochemistry , 50 11 , Huynh and Paul F. Biochemistry , 49 35 , Panay and Paul F. Journal of the American Chemical Society , 16 ,