Dataset Information

Phosphatidylcholine formation by LPCAT1 is regulated by Ca(2+) and the redox status of the cell.

ABSTRACT:

Background

Unsaturated fatty acids are susceptible to oxidation and damaged chains are removed from glycerophospholipids by phospholipase A(2). De-acylated lipids are then re-acylated by lysophospholipid acyltransferase enzymes such as LPCAT1 which catalyses the formation of phosphatidylcholine (PC) from lysoPC and long-chain acyl-CoA.

Results

Activity of LPCAT1 is inhibited by Ca(2+), and a Ca(2+)-binding motif of the EF-hand type, EFh-1, was identified in the carboxyl-terminal domain of the protein. The residues Asp-392 and Glu-403 define the loop of the hairpin structure formed by EFh-1. Substitution of D(392) and E(403) to alanine rendered an enzyme insensitive to Ca(2+), which established that Ca(2+) binding to that region negatively regulates the activity of the acyltransferase amino-terminal domain. Residue Cys-211 of the conserved motif III is not essential for catalysis and not sufficient for sensitivity to treatment by sulfhydryl-modifier agents. Among the several active cysteine-substitution mutants of LPCAT1 generated, we identified one to be resistant to treatment by sulfhydryl-alkylating and sulfhydryl-oxidizer agents.

Conclusion

Mutant forms of LPCAT1 that are not inhibited by Ca(2+) and sulfhydryl-alkylating and -oxidizing agents will provide a better understanding of the physiological function of a mechanism that places the formation of PC, and the disposal of the bioactive species lysoPC, under the control of the redox status and Ca(2+) concentration of the cell.

SUBMITTER: Soupene E

PROVIDER: S-EPMC3439698 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phosphatidylcholine formation by LPCAT1 is regulated by Ca(2+) and the redox status of the cell.

Soupene Eric E Kuypers Frans A FA

BMC biochemistry 20120607

<h4>Background</h4>Unsaturated fatty acids are susceptible to oxidation and damaged chains are removed from glycerophospholipids by phospholipase A(2). De-acylated lipids are then re-acylated by lysophospholipid acyltransferase enzymes such as LPCAT1 which catalyses the formation of phosphatidylcholine (PC) from lysoPC and long-chain acyl-CoA.<h4>Results</h4>Activity of LPCAT1 is inhibited by Ca(2+), and a Ca(2+)-binding motif of the EF-hand type, EFh-1, was identified in the carboxyl-terminal d ...[more]

PMID: 22676268

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Dataset Information

Phosphatidylcholine formation by LPCAT1 is regulated by Ca(2+) and the redox status of the cell.

Background

Results

Conclusion

Publications

Phosphatidylcholine formation by LPCAT1 is regulated by Ca(2+) and the redox status of the cell.

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