Specific objectives of this application are: (1) to determine the mechanism of how ethanolamine plasmalogens are synthesized from an intact alkyl phospholipid by a 1-alkyl desaturase, (2) to identify the factors that influence branchpoints and to identify the rate-limiting steps in the metabolic pathways for glycerolipids that determine membrane lipid composition with respect to the diacyl-, alkylacyl-, and alk-l-enylacyl- subclasses of phospholipids, and (3) to characterize the properties and to delineate the reaction mechanism and regulatory role of the enzymes that cleave the alkyl (Pte.H4-dependent alkyl monooxygenase) and alk-1-enyl (plasmalogenase) ether bonds in glycerolipids. The studies of the desaturase and the cleavage enzymes are expected to be done with purified preparations of the enzymes. Results of this work are expected to extend our basic understanding of the metabolism of lipids with ether-linked chains, including those phospholipids that are precursors of the alkylacetylated types (e.g., platelet activating factor) that exhibit potent biological activities. Information from these experiments are also expected to explain why ether lipids are characteristically elevated in most cancer cells and could shed light on their functional role in cell membranes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041642-04
Application #
3182372
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1986-09-30
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Oak Ridge Associated Universities
Department
Type
DUNS #
City
Oak Ridge
State
TN
Country
United States
Zip Code
37831
Snyder, F (1992) Alkylglycerol phosphotransferase. Methods Enzymol 209:211-5
Blank, M L; Snyder, F (1992) Plasmanylethanolamine delta 1-desaturase. Methods Enzymol 209:390-6
Brown, A; Snyder, F (1992) Alkyldihydroxyacetonephosphate synthase. Methods Enzymol 209:377-84
Lee, T C; Vallari, D S; Snyder, F (1992) 1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase. Methods Enzymol 209:396-401
Lee, T C; Blank, M L; Fitzgerald, V et al. (1991) Acylation of alkyllysophospholipids by Fischer sarcoma microsomes. Arch Biochem Biophys 288:600-8
Lee, T C; Qian, C G; Snyder, F (1991) Biosynthesis of choline plasmalogens in neonatal rat myocytes. Arch Biochem Biophys 286:498-503
Blank, M L; Snyder, F (1991) Chromatographic analysis of phospholipase reaction products. Methods Enzymol 197:158-65
Kasama, K; Blank, M L; Snyder, F (1989) Identification of 1-alkyl-2-acyl-3-(2',3'-diacylglycerol)glycerols, a new type of lipid class, in harderian gland tumors of mice. J Biol Chem 264:9453-61
Blank, M L; Smith, Z L; Lee, Y J et al. (1989) Effects of eicosapentaenoic and docosahexaenoic acid supplements on phospholipid composition and plasmalogen biosynthesis in P388D1 cells. Arch Biochem Biophys 269:603-11