Document Detail

Substrate preference in phosphatidylserine biosynthesis for docosahexaenoic acid containing species.
MedLine Citation:
PMID:  14744148     Owner:  NLM     Status:  MEDLINE    
Neuronal membranes contain high levels of phosphatidylserine (PS) and docosahexaenoic acid (22:6n-3, DHA). In this study, substrate preference in PS synthesis was determined to gain insight on the biochemical basis for concentrating PS in neuronal membranes where 22:6n-3 is highly enriched. We first established an in vitro assay method using unilamellar vesicles (LUV) of deuterium-labeled substrates and reversed-phase HPLC/electrospray ionization (ESI) mass spectrometry. The PS production by the incubation of deuterium-labeled substrate and microsomal fractions was monitored. We found that tissue-specific substrate preference exists in PS synthesis. Microsomes from the cerebral cortex synthesized PS from 18:0,22:6-PC most favorably among the PC substrates tested, followed by 18:0,22:5-PC, resulting in the PC substrate preference in the order of 18:0,22:6 > 18:0,22:5 > 18:0,20:4 = 18:0,18:1. Liver microsomes also preferred 18:0,22:6-PC as the substrate in PS synthesis but did not use 18:0,22:5-PC favorably. The 18:0,22:5-PC species was converted to PS at the similar extent as 18:0,20:4- or 18:0,18:1-PC species in the liver. Both brain and liver microsomes showed a preference for 18:0 over 16:0 as the sn-1 fatty acid. From these data it was deduced that preferential conversion of 18:0,22:6-PC to the corresponding PS species is at least partly responsible for concentrating PS in neuronal tissues where 22:6n-3 is particularly abundant. The distinctive preference for 18:0,22:5-PS observed with brain microsomes may help to maintain PS at a high level in the brain when 22:6n-3 is replaced by 22:5n-3 as in the case of n-3 fatty acid deficiency.
Hee-Yong Kim; James Bigelow; Jillonne H Kevala
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemistry     Volume:  43     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-27     Completed Date:  2004-05-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1030-6     Citation Subset:  IM    
Section of Mass Spectrometry, Laboratory of Membrane Biochemistry and Biophysics, NIAAA, National Institutes of Health, Rockville, Maryland 20852, USA.
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MeSH Terms
Cerebral Cortex / chemistry,  metabolism
Chromatography, High Pressure Liquid
Deuterium / chemistry
Docosahexaenoic Acids / chemistry*,  metabolism
Lipid Bilayers / chemistry
Microsomes / chemistry,  metabolism*
Microsomes, Liver / chemistry,  metabolism
Phosphatidylcholines / chemistry
Phosphatidylserines / biosynthesis*
Serine / chemistry
Spectrometry, Mass, Electrospray Ionization
Substrate Specificity
Reg. No./Substance:
0/Lipid Bilayers; 0/Phosphatidylcholines; 0/Phosphatidylserines; 25167-62-8/Docosahexaenoic Acids; 56-45-1/Serine; 7782-39-0/Deuterium

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