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Journal of Lipid Research, Vol. 46, 727-735, April 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Role of dihydroxyacetonephosphate acyltransferase in the biosynthesis of plasmalogens and nonether glycerolipids

Dailan Liu^*, Narasimhan Nagan^1,*, Wilhelm W. Just, Claus Rodemer, Thanh-Phuong Thai and Raphael A. Zoeller^2,*

^* Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118
Biochemie-Zentrum, Universitat Heidelberg, D-69120 Heidelberg, Germany

² To whom correspondence should be addressed. e-mail: rzoeller{at}bu.edu

The variant CHO-K1 cell line, NRel-4, is unable to synthesize plasmalogens because of a severe reduction in dihydroxyacetonephosphate acyltransferase (DHAPAT) activity (Nagan, N., A. K. Hajra, L. K. Larkins, P. Lazarow, P. E. Purdue, W. B. Rizzo, and R. A. Zoeller. 1998. Isolation of a Chinese hamster fibroblast variant defective in dihydroxyacetonephosphate acyltransferase activity and plasmalogen biosynthesis: use of a novel two-step selection protocol. Biochem. J. 332: 273–279). Northern analysis demonstrated that the loss of this activity was attributable 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, whereas in one isolate, NRel-4.15, which overexpressed DHAPAT activity by 6-fold over wild-type cells, plasmalogen levels were returned only to wild-type values. Although the rate of plasmenylethanolamine biosynthesis was restored in NRel-4.15, the biosynthesis of nonether glycerolipids was either decreased or unaffected, suggesting that peroxisomal DHAPAT does not normally contribute to nonether glycerolipid biosynthesis.

These 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.

Abbreviations: DHAP, dihydroxyacetonephosphate; DHAPAT, dihydroxyacetonephosphate acyltransferase; Gro-3-P, glycerol-3-phosphate; Gro-3-PAT, glycerol-3-phosphate acyltransferase; Pi, inorganic phosphate; PTS1, peroxisome targeting signal type 1; SSC, saline-sodium citrate buffer

Supplementary key words glycerol-3-phosphate acyltransferase • variant • Chinese hamster ovary cells

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