Plasma free and sulfoconjugated catecholamines in healthy men

Cuche, Jean-Louis; Prinseau, J; Ruget, G; Selz, Françoise; Tual, J.L.; Baglin, A; Guédon, J; Fritel, D

doi:10.1093/eurheartj/3.suppl_c.3

Cited by 5 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SULT substrate specificities are typically broad, overlapping, and centered on different areas of metabolism. The diversity of function across SULT isoforms results in a remarkably broad range of metabolic functions including potent regulation of steroids (4), thyroid (5) and peptide hormones (6), oxysterols (7), pheromones (8), selectins (9), and neurotransmitters (10,11).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Tetrahydrobiopterin regulates monoamine neurotransmitter sulfonation

Cook

Wang

Leyh

2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Monoamine neurotransmitters are among the hundreds of signaling small molecules whose target interactions are switched "on" and "off" via transfer of the sulfuryl-moiety (-SO 3 ) from PAPS (3′-phosphoadenosine 5′-phosphosulfate) to the hydroxyls and amines of their scaffolds. These transfer reactions are catalyzed by a small family of broad-specificity enzymes-the human cytosolic sulfotransferases (SULTs). The first structure of a SULT allosteric-binding site (that of SULT1A1) has recently come to light. The site is conserved among SULT1 family members and is promiscuous-it binds catechins, a naturally occurring family of flavanols. Here, the catechin-binding site of SULT1A3, which sulfonates monoamine neurotransmitters, is modeled on that of 1A1 and used to screen in silico for endogenous metabolite 1A3 allosteres. Screening predicted a single high-affinity allostere, tetrahydrobiopterin (THB), an essential cofactor in monoamine neurotransmitter biosynthesis. THB is shown to bind and inhibit SULT1A3 with high affinity, 23 (±2) nM, and to bind weakly, if at all, to the four other major SULTs found in brain and liver. The structure of the THB-bound binding site is determined and confirms that THB binds the catechin site. A structural comparison of SULT1A3 with SULT1A1 (its immediate evolutionary progenitor) reveals how SULT1A3 acquired high affinity for THB and that the majority of residue changes needed to transform 1A1 into 1A3 are clustered at the allosteric and active sites. Finally, sequence records reveal that the coevolution of these sites played an essential role in the evolution of simian neurotransmitter metabolism.sulfotransferase | tetrahydrobiopterin | neurotransmitter | allostery | evolution H uman cytosolic sulfotransferases (SULTs) regulate the activities of thousands of endogenous small-molecule metabolites and xenobiotics via transfer of the sulfuryl-moiety (-SO 3 ) to and from the hydroxyl-and amine-moieties of these acceptors. The 13 full-length SULT isoforms encoded in the human genome are expressed in tissue-and developmentally specific patterns (1-3). SULT substrate specificities are typically broad, overlapping, and centered on different areas of metabolism. The diversity of function across SULT isoforms results in a remarkably broad range of metabolic functions including potent regulation of steroids (4), thyroid (5) and peptide hormones (6), oxysterols (7), pheromones (8), selectins (9), and neurotransmitters (10, 11).Although recent work has deepened our understanding of SULT small-molecule allosteric regulation, the topic remains largely unexplored (12-16). The catechin-binding site is the most well-characterized SULT allosteric site (12). Catechins, a complex biomorphic family of SULT allosteric inhibitors, are found at high levels in tea leaves, cocoa, and coffee (17-19). The binding site is promiscuous in that it binds numerous catechins (15, 20) and related structures. The structure of the SULT1A1 catechin-binding site, the only published SULT allosteric-site structure, has recentl...

show abstract

mentioning

confidence: 99%

“…THB participates in the O 2 -cleavage reaction of aromatic amino acid hydroxylases, which rate-limit monoamine neurotransmitter biosynthesis. The sulfonation of such transmitters is extensive and tissue-dependent (11,(21)(22)(23)(24). When tested, THB proved a potent (K i , 23 nM) and highly selective allosteric inhibitor of SULT1A3.…”

mentioning

confidence: 99%