Linked Life Data

2471088

Source:http://linkedlifedata.com/resource/pubmed/id/2471088

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1989-7-7
pubmed:abstractText
The inhibition of dansylsarcosine (DS) binding at the benzodiazepine binding site of human serum albumin has been studied in the presence of saturated and unsaturated free fatty acids (FFA) of various chain lengths (C6-C20, C18:1, C18:2). In order to determine the mechanism of displacement, velocity constants for association (k2) and dissociation (k-2) and binding constants (KA and KA') have been measured using the stopped-flow method. The inhibitory effect of FFA on DS binding kinetics at site II is dependent of their structure. With increasing amounts of FFA the association velocity constant of DS binding decreases from 520 s-1 (fatty acid free albumin) by a factor of 3-10 and affinity decreases according to FFA chain length. Inhibition is strongest in the presence of caprylic, capric and lauric acid (C8-C12) i.e. with more than one mole FFA per mole albumin, DS association could no longer be measured. Short chain caproic and the long chain FFA C14-C20 showed only a less inhibitory effect since in the presence of a twofold excess k2 ranged between 100 and 200 s-1. Dissociation velocity of DS from the benzodiazepine binding site could be measured in relationship to FFA chain length using ibuprofene, another drug binding at site II. Dissociation velocity constants k-2 remained constant up to 2 moles FFA per mole albumin (k-2 = 16-18 s-1). A rise in k-2 to 70 s(-1) was seen, however, when 2-4 moles capric, lauric, myristic and palmitic (C10-C16) acid were bound, whereas no change was observed when increasing concentrations of caproic, caprylic, stearic and arachic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
339
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
42-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:articleTitle
Kinetics of drug binding to human serum albumin: allosteric and competitive inhibition at the benzodiazepine binding site by free fatty acids of various chain lengths.
pubmed:affiliation
Abteilung für Klinische Pharmakologie am Klinikum, Johann-Wolfgang-Goethe-Universität Frankfurt am Main. Federal Republic of Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't