Document Detail


Determination by photoreduction of flip-flop kinetics of spin-labeled stearic acids across phospholipid bilayers.
MedLine Citation:
PMID:  9889351     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Spin-labeled stearic acid derivatives (N-DS) can be used to determine the rate at which lipid-derived drugs can cross a phospholipid bilayer (flip-flop). The flip-flop rate of N-DS (where N=5, 6, 7, 9, 10, 12, 16), was measured using vectorial photoreduction of nitroxides to their corresponding hydroxylamine by FMN, a charged, membrane-impermeable flavin, by hydrogen atom transfer from EDTA. From the time difference in the photoreduction rates of N-DS located in the outer and inner half of the bilayer, the flip-flop rate of N-DS across the bilayer can be determined. The results show that at pH 8.0 or lower, the photoreduction of 5-DS on one side of the membrane by FMN is slower than the flip-flop rate of 5-DS across phospholipid bilayers. For 5-DS at pH 7.0, this rate is at least 33.8+/-4.24 s or faster. Stearic acids with the spin label at different positions along the acyl chain (N=5, 6, 7, 9, 10, 12) have similar flip-flop rates in the liposomes at pH 7.0 although 16-DS is slower, probably due to the inaccessibility of the nitroxide moiety to FMN. It is most likely that the fast distribution of 5-DS in cells is due to the fast movement of acidic form, but not the salt form, of 5-DS across membrane bilayers. The oxazolidine (nitroxide moiety) does not seem to affect the pKa ( approximately 8.3) of stearic acid at air-water interface. Thus, N-DS are good probes for studying the distribution kinetics of stearic acid derivatives in biological systems.
Authors:
J M Yuann; R D Morse
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1416     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-02-23     Completed Date:  1999-02-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  135-44     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Illinois State University, Normal, IL 61790-4160, USA. jyuann@chem.bu.edu
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MeSH Terms
Descriptor/Qualifier:
Cyclic N-Oxides
Electron Spin Resonance Spectroscopy
Flavin Mononucleotide / chemistry
Lipid Bilayers / chemistry*
Membrane Fluidity
Oxidation-Reduction
Permeability
Phospholipids / chemistry*
Spin Labels
Stearic Acids / chemistry*
Temperature
Grant Support
ID/Acronym/Agency:
GM 1415-44365-01/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cyclic N-Oxides; 0/Lipid Bilayers; 0/Phospholipids; 0/Spin Labels; 0/Stearic Acids; 146-17-8/Flavin Mononucleotide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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