Role of dihydroxyacetonephosphate acyltransferase in the biosynthesis of plasmalogens and non-ether glycerolipids: Studies using a plasmalogen-deficient CHO-K1 variant

Dailan Liu, Narasimhan Nagan, Wilhelm W. Just, Claus Rodemer, Thanh-Phuong Thai, and Raphael A. Zoeller

Department of Physiology and Biophysics, Boston University, Boston, MA 02118

Corresponding Author: rzoeller{at}bu.edu

The variant Chinese hamster ovary (CHO-K1) cell line, NRel-4, is unable to synthesize plasmalogens due to a severe reduction in dihydroxyacetonephosphate acyltransferase (DHAPAT) activity [Nagan, N. et al. (1998) Biochem. J. 332, 273-279]. Northern analysis demonstrated that the loss of this activity was due to a severe reduction in mRNA levels for DHAPAT. Transfection of NRel-4 cells with a plasmid bearing the human DHAPAT cDNA recovered DHAPAT activity and plasmalogen biosynthesis. Examination of clonal isolates from the transfected population showed that recovery of as little as 10% of wild type DHAPAT activity restored plasmalogen levels to 55% of normal while in one isolate, NRel-4.15, which over-expressed DHAPAT activity 6-fold over wild-type cells, plasmalogen levels were returned only to wild-type values. While the rate of plasmenylethanolamine biosynthesis was restored in NRel-4.15, the biosynthesis of non-ether glycerolipids was either decreased or unaffected suggesting that peroxisomal DHAPAT does not normally contribute to non-ether glycerolipid biosynthesis. The data demonstrate that a defect in the gene that codes for peroxisomal DHAPAT is the primary lesion in the NRel-4 cell line and that the peroxisomal DHAPAT is essential for the biosynthesis of plasmalogens in animal cells.

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