Concerted action of the cytosolic sulfotransferase, SULT1A3, and catechol-O-methyltransferase in the metabolism of dopamine in SK-N-MC human neuroblastoma cells.

Abstract

Conjugation reactions catalyzed by the cytosolic sulfotransferase, SULT1A3, or catechol-O-methyltransferase (COMT) are known to be involved in the regulation and homeostasis of dopamine and other monoamine neurotransmitters. Whether different conjugation reactions may act in a concerted manner, however, remains unclear. The current study aimed to investigate the concerted action of SULT1A3 and COMT in dopamine metabolism. Analysis of the medium of SK-N-MC cells, metabolically labeled with [(35)S]sulfate in the presence of dopamine, revealed the generation and release of predominantly [(35)S]sulfated 3-methyldopamine and, to a lesser extent [(35)S]sulfated dopamine. Addition to the labeling medium of tropolone, a COMT inhibitor, enhanced the production of [(35)S]sulfated dopamine, with a concomitant decrease of [(35)S]sulfated 3-methyldopamine. Enzymatic assays using the eleven known human cytosolic SULTs revealed SULT1A3 as the major enzyme responsible for the sulfation of both dopamine and 3-methyldopamine. Kinetic analysis showed that the catalytic efficiency of SULT1A3 with 3-methyldopamine was 1.6 times than that with dopamine. Using subcellular fractions prepared from SK-N-MC cells, the majority of COMT dopamine-methylating activity was found to be present in the cytosol. Collectively, these results imply a concerted action of sulfation and methylation in the irreversible inactivation and disposal of excess dopamine in SK-N-MC cells.

• Authors: Shin Yasuda, Tomoko Yasuda, Ying Hui, Ming-Yih Liu, Masahito Suiko, Yoichi Sakakibara, Ming-Cheh Liu
• Journal: Neuroscience research (Neurosci Res) Vol. 64 Issue 3 Pg. 273-9 (Jul 2009) ISSN: 1872-8111 [Electronic] Ireland
• PMID: 19447296 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catechol O-Methyltransferase Inhibitors
• Sulfates
• Tropolone
• Catechol O-Methyltransferase
• Sulfotransferases
• Arylsulfotransferase
• monoamine-sulfating phenol sulfotransferase
• Deoxyepinephrine
• Dopamine

Topics

• Arylsulfotransferase
• Catechol O-Methyltransferase (metabolism)
• Catechol O-Methyltransferase Inhibitors
• Cell Line
• Cytosol (enzymology)
• Deoxyepinephrine (metabolism)
• Dopamine (metabolism)
• Homeostasis
• Humans
• Isotope Labeling
• Methylation (drug effects)
• Neurons (enzymology)
• Protein Processing, Post-Translational (drug effects)
• Substrate Specificity
• Sulfates (metabolism)
• Sulfotransferases (metabolism)
• Tropolone (pharmacology)