Tyrosine Hydroxylase

Jamshed Arslan, Pharm D, PhD

Tyrosine hydroxylase (TH) is a crucial enzyme involved in the biosynthesis of dopamine, norepinephrine and epinephrine in the brain.

Tyrosine hydroxylase is a member of the aromatic amino acid hydroxylase (AAAH) family.  It is expressed throughout the central nervous system (CNS) and catalyzes the conversion of tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), which can be, through a series of downstream enzymatic reactions, processed into the neurotransmitter and signaling molecule dopamine. Dopamine can then be further altered to produce norepinephrine or epinephrine.

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.

In the synthesis pathway for the catecholamines - dopamine, epinephrine, and norepinephrine, tyrosine hydroxylase is the rate-limiting enzyme. Through alternative mRNA splicing, a wide molecular diversity of TH isoforms are generated that are tissue-specific and carry varied enzymatic activities, allowing for differential neurotransmitter availability at various synapses.

Tyrosine hydroxylase is the rate-limiting enzyme in the synthesis pathway of the catecholamines dopamine, epinephrine, and norepinephrine.

 Tyrosine hydroxylase catalyzes the rate-limiting step in the biosynthesis of the catecholamines dopamine, norepinephrine, and epinephrine. A hallmark of Parkinson's disease is the loss of dopaminergic neurons in the substantia nigra. Mutations in cases of autosomal recessive dopa-responsive dystonia and infantile Parkinsonism have also been identified recently.