Substrate preference in phosphatidylserine biosynthesis for docosahexaenoic acid containing species

Biochemistry. 2004 Feb 3;43(4):1030-6. doi: 10.1021/bi035197x.


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.

MeSH terms

  • Animals
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / metabolism
  • Chromatography, High Pressure Liquid
  • Deuterium / chemistry
  • Docosahexaenoic Acids / chemistry*
  • Docosahexaenoic Acids / metabolism
  • Lipid Bilayers / chemistry
  • Microsomes / chemistry
  • Microsomes / metabolism*
  • Microsomes, Liver / chemistry
  • Microsomes, Liver / metabolism
  • Phosphatidylcholines / chemistry
  • Phosphatidylserines / biosynthesis*
  • Rats
  • Serine / chemistry
  • Spectrometry, Mass, Electrospray Ionization
  • Substrate Specificity


  • Lipid Bilayers
  • Phosphatidylcholines
  • Phosphatidylserines
  • Docosahexaenoic Acids
  • Serine
  • Deuterium