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Tyrosinase: a developmentally specific major determinant of peripheral dopamine
Graeme Eisenhofer1, Hua Tian, Courtney Holmes
1Section on Clinical Neurocardiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Dr. MSC 1620, Bethesda, MD 20892-1620, USA. ge@box-g.nih.gov
Summary
Tyrosinase, an enzyme in melanocytes, independently produces dopamine in young mice, a pathway that diminishes with age. This highlights a transient, non-tyrosine hydroxylase-dependent source of dopamine.
Area of Science:
- Biochemistry
- Neuroscience
- Developmental Biology
Background:
- L-3,4-dihydroxyphenylalanine is the dopamine precursor, synthesized by tyrosine hydroxylase (TH) in neurons and tyrosinase in melanocytes.
- The role of tyrosinase in dopamine production, independent of TH, remains largely unexplored.
Purpose of the Study:
- To investigate the contribution of tyrosinase to peripheral dopamine synthesis.
- To examine age-related changes in dopamine production and tyrosinase activity in mice.
Main Methods:
- Analysis of dopamine and norepinephrine levels in TH-deficient and wild-type albino and pigmented mice.
- Assessment of age-related changes in cutaneous tyrosinase expression and melanin production.
Main Results:
- TH deficiency reduced norepinephrine but only partially reduced dopamine in albino mice.
- Pigmented mice exhibited higher peripheral dopamine than albino mice, irrespective of TH levels.
- In young mice, tyrosinase produced dopamine; with age, tyrosinase shifted to melanin production, decreasing dopamine synthesis.
Conclusions:
- A significant TH-independent pathway for peripheral dopamine synthesis exists in young mice, mediated by tyrosinase.
- This pathway is transient, reflecting a developmental switch from dopamine to melanin production by tyrosinase.