Tyrosine Hydroxylase - rate-limiting enzyme in catecholamine synthesis

Tue, 09/08/2015 - 14:01

Catecholamines are tyrosine-derived hormones that are produced in the adrenal gland. They include epinephrine, norepinephrine, and dopamine and are used as neurotransmitters by the central and peripheral nervous system. The rate limiting enzyme in catecholamine synthesis is Tyrosine Hydroxylase. Tyrosine Hydroxylase is responsible for the conversion of tyrosine to L-DOPA, which is readily converted into dopamine. Epinephrine and Norepinephrine are then further derived from dopamine. Tyrosine Hydroxylase is a member of the aromatic amino acid hydroxylase family (AAAH) which also includes Phenylalanine Hydroxylase and Tryptophan Hydroxylase. All of the AAAH enzymes contain an N-terminal regulatory domain, a catalytic domain, and a C-terminal coiled-coil domain responsible for enzyme tetramerization (1).  Tyrosine Hydroxylase is highly regulated to control catecholamine levels within the body. It is susceptible to negative feedback inhibition by catecholamines; however, this inhibition is blunted when the regulatory domain is phosphorylated at one of four serine residues by PKA, ERK1/2, or MAPKAPK2. Four isoforms of Tyrosine Hydroxylase exist due to alternative mRNA splicing of the regulatory domain. These isoforms are expressed in different ratios to confer unique signaling specificity to different tissues. Mutations in the Tyrosine Hydroxylase gene have been linked to neurological disorders such as Parkinson’s, Alzheimer’s, and schizophrenia.

Xu et. al. first used the Tyrosine Hydroxylase (pSer31) antibody in 1998 to map the localization of the different phospho-isotypes in sections of rat brain (2). The group described the antibody specificity and verified a process for using it in vitro and in vivo. Shortly after in 1999, Lew et. al. used another Tyrosine Hydroxylase antibody to better understand the regulation mechanisms behind site-specific phosphorylation (3). The group used the Tyrosine Hydroxylase (pSer40) antibody to look at phosphorylated levels during treatment with dopamine signaling inhibitors. They found that inhibition of dopamine signaling led to a significant increase of phospho-Ser40 and phospho-Ser19, which ultimately increased catecholamine production. More recently, groups have been using the Tyrosine Hydroxylase antibodies to understand its role in various pathological conditions. Ahmed et. al. used the Tyrosine Hydroxylase antibody to help develop a model for studying impaired autophagy in Parkinson’s disease (4). Given its important role in nervous system signaling, Tyrosine Hydroxylase is being studied in the setting of many neurological conditions.

Novus Biologicals offers Tyrosine Hydroxylase reagents for your research needs including:


  1. 21176768
  2. 9483531
  3. 9927609
  4. 23152632

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