Linked Life Data

10800950

Source:http://linkedlifedata.com/resource/pubmed/id/10800950

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-5-25
pubmed:abstractText
Tryptophan hydroxylase (TPH) is the initial and rate-limiting enzyme in serotonin biosynthesis. The enzyme activity is dependent on molecular oxygen, a tetrahydropterin cosubstrate, and ferrous iron. The present study demonstrates that TPH is inhibited by a novel compound, p-ethynylphenylalanine (pEPA), produced by the Heck reaction of trimethylsilylacetylene with N-tertbutyloxycarbonyl-4-iodo-L-phenylalanine methyl ester. pEPA is a more potent and specific inhibitor of TPH than p-chlorophenylalanine (pCPA). In the present study, pEPA was demonstrated to inhibit competitively and reversibly TPH in vitro (Ki = 32.6 +/- 6.2 microM vs. tryptophan). pEPA displayed little inhibitory activity toward tyrosine hydroxylase (EC 1.14.16.2), the initial and rate-limiting enzyme for catecholamine biosynthesis, and no inhibition of phenylalanine hydroxylase or tyrosinase. In addition, pEPA was a poor ligand for the serotonin transporter and several serotonin receptors. Administration of pEPA (30 mg/kg) to rats produced a 95 +/- 5% decrease in TPH activity in brain homogenates and a concomitant decrease in serotonin and 5-hydroxyindole-3-acetic acid levels (85%) at 24 h after injection. In contrast, pCPA produced a similar effect (87 +/- 5% decrease in TPH activity) only at 10 times the concentration (300 mg/kg). These results suggest that pEPA is a selective, reversible, and potent inhibitor of TPH both in vitro and in vivo. The potential for pEPA to inhibit selectively and reversibly the biosynthesis of serotonin may contribute to the characterization of the role of serotonin in behavioral and physiological activities.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2067-73
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10800950-Alanine, pubmed-meshheading:10800950-Animals, pubmed-meshheading:10800950-Brain, pubmed-meshheading:10800950-Enzyme Inhibitors, pubmed-meshheading:10800950-Fenclonine, pubmed-meshheading:10800950-Humans, pubmed-meshheading:10800950-Hydroxyindoleacetic Acid, pubmed-meshheading:10800950-Infant, Newborn, pubmed-meshheading:10800950-Kinetics, pubmed-meshheading:10800950-Male, pubmed-meshheading:10800950-Rabbits, pubmed-meshheading:10800950-Rats, pubmed-meshheading:10800950-Rats, Inbred F344, pubmed-meshheading:10800950-Rats, Sprague-Dawley, pubmed-meshheading:10800950-Recombinant Proteins, pubmed-meshheading:10800950-Serotonin, pubmed-meshheading:10800950-Serotonin Antagonists, pubmed-meshheading:10800950-Tryptophan Hydroxylase, pubmed-meshheading:10800950-Tyrosine 3-Monooxygenase
pubmed:year
2000
pubmed:articleTitle
p-ethynylphenylalanine: a potent inhibitor of tryptophan hydroxylase.
pubmed:affiliation
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't