Skip to main content
SpringerLink
Log in

Substrate Preferences of a Lysophosphatidylcholine Acyltransferase Highlight Its Role in Phospholipid Remodeling

  • Original Article
  • Published:
Lipids

Abstract

An important enzyme involved in phospholipid turnover is the acyl-CoA: lysophosphatidylcholine acyltransferase (LPCAT). Here, we report characterization of a newly discovered human LPCAT (LPCAT3), which has distinct substrate preferences strikingly consistent with a role in phosphatidylcholine (PtdCho) remodeling and modulating fatty acid composition of PtdCho. LPCAT3 prefers lysophosphatidylcholine (lysoPtdCho) with saturated fatty acid at the sn-1 position and exhibits acyl donor preference towards linoleoyl-CoA and arachidonoyl-CoA. Furthermore, LPCAT3 is active in mediating 1-O-alkyl-sn-glycero-3-phosphocholine acylation with long chain fatty acyl-CoAs to generate 1-O-alkyl-phosphatidylcholine, another very important constitute of mammalian membrane systems. These properties are precisely the known attributes of LPCAT previously ascribed to the isoform involved in Lands' cycle, and thus strongly suggest that LPCAT3 is involved in phospholipids remodeling to achieve appropriate membrane lipid fatty acid composition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

DAG:

Diacylglycerol

CDP-choline:

Cytidine 5′-diphosphocholine

CDP-DAG:

Cytidine 5′-diacylglycerol

EUROSCARF:

European Saccharomyces cerevisiae archive for functional analysis

LPCAT3:

Human acyl-CoA: lysophosphatidylcholine acyltransferase

LCA1:

Yeast lysophosphatidylcholine acyltransferase

LysoPA:

Lysophosphatidic acid

LPCAT:

Acyl-CoA: lysophosphatidylcholine acyltransferase

LysoPtdCho:

Lysophosphatidylcholine

LysoPtdEtn:

Lysophosphatidylethanolamine

LysoPtdGro:

Lysophosphatidylglycerol

MBOAT:

Membrane-bound O-acyltransferase

PAF:

Platelet-activating factor

PtdCho:

Phosphatidylcholine

References

  1. Carman GM, Henry SA (1999) Phospholipid biosynthesis in the yeast Saccharomyces cerevisiae and interrelationship with other metabolic processes. Prog Lipid Res 38:361–399

    Article  PubMed  CAS  Google Scholar 

  2. Chen Q, Kazachkov M, Zheng Z, Zou J (2007) The yeast acylglycerol acyltransferase LCA1 is a key component of Lands cycle for phosphatidylcholine turnover. FEBS Lett 581:5511–5516

    Article  PubMed  CAS  Google Scholar 

  3. Choy PC, Skrzypczak M, Lee D, Jay FT (1997) Acyl-GPC and alkenyl/alkyl-GPC:acyl-CoA acyltransferases. Biochim Biophys Acta 1348:124–133

    PubMed  CAS  Google Scholar 

  4. Lands WE (1960) Metabolism of glycerolipids. 2. The enzymatic acylation of lysolecithin. J Biol Chem 235:2233–2237

    PubMed  CAS  Google Scholar 

  5. Chen X, Hyatt BA, Mucenski ML, Mason RJ, Shannon JM (2006) Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells. Proc Natl Acad Sci USA 103:11724–11729

    Article  PubMed  CAS  Google Scholar 

  6. Nakanishi H, Shindou H, Hishikawa D, Harayama T, Ogasawara R, Suwabe A, Taguchi R, Shimizu T (2006) Cloning and characterization of mouse lung-type acyl-CoA:lysophosphatidylcholine acyltransferase 1 (LPCAT1). Expression in alveolar type II cells and possible involvement in surfactant production. J Biol Chem 281:20140–20147

    Article  PubMed  CAS  Google Scholar 

  7. Shindou H, Hishikawa D, Nakanishi H, Harayama T, Ishii S, Taguchi R, Shimizu T (2007) A single enzyme catalyzes both platelet-activating factor production and membrane biogenesis of inflammatory cells. Cloning and characterization of acetyl-CoA:LYSO-PAF acetyltransferase. J Biol Chem 282:6532–6539

    Article  PubMed  CAS  Google Scholar 

  8. Soupene E, Fyrst H, Kuypers FA (2008) Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes. Proc Natl Acad Sci USA 105:88–93

    Article  PubMed  CAS  Google Scholar 

  9. Lewin TM, Wang P, Coleman RA (1999) Analysis of amino acid motifs diagnostic for the sn-glycerol-3-phosphate acyltransferase reaction. Biochemistry 38:5764–5771

    Article  PubMed  CAS  Google Scholar 

  10. Benghezal M, Roubaty C, Veepuri V, Knudsen J, Conzelmann A (2007) SLC1 and SLC4 encode partially redundant acyl-coenzyme A 1-acylglycerol-3-phosphate O-acyltransferases of budding yeast. J Biol Chem 282:30845–30855

    Article  PubMed  CAS  Google Scholar 

  11. Jain S, Stanford N, Bhagwat N, Seiler B, Costanzo M, Boone C, Oelkers P (2007) Identification of a novel lysophospholipid acyltransferase in Saccharomyces cerevisiae. J Biol Chem 282:30562–30569

    Article  PubMed  CAS  Google Scholar 

  12. Riekhof WR, Wu J, Jones JL, Voelker DR (2007) Identification and characterization of the major lysophosphatidylethanolamine acyltransferase in Saccharomyces cerevisiae. J Biol Chem 282:28344–28352

    Article  PubMed  CAS  Google Scholar 

  13. Tamaki H, Shimada A, Ito Y, Ohya M, Takase J, Miyashita M, Miyagawa H, Nozaki H, Nakayama R, Kumagai H (2007) LPT1 encodes a membrane-bound O-acyltransferase involved in the acylation of lysophospholipids in the yeast Saccharomyces cerevisiae. J Biol Chem 282:34288–34298

    Article  PubMed  CAS  Google Scholar 

  14. Zhao Y, Chen Y, Bonacci TM, Bredt DS, Li S, Bensch WR, Moller DE, Kowala M, Konrad RJ, Cao G (2008) Identification and characterization of a lysophosphatidylcholine acyltransferase that is primarily expressed in metabolic tissues. J Biol Chem 283:8258–8265

    Article  PubMed  CAS  Google Scholar 

  15. Hishikawa D, Shindou H, Kobayashi S, Nakanishi H, Taguchi R, Shimizu T (2008) Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity. Proc Natl Acad Sci USA 105:2830–2835

    Article  PubMed  CAS  Google Scholar 

  16. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    PubMed  CAS  Google Scholar 

  17. Lee HC, Inoue T, Imae R, Kono N, Shirae S, Matsuda S, Gengyo-Ando K, Mitani S, Arai H (2008) Caenorhabditis elegans mboa-7, a member of the MBOAT family, is required for selective incorporation of polyunsaturated fatty acids into phosphatidylinositol. Mol Biol Cell 19:1174–1184

    Article  PubMed  CAS  Google Scholar 

  18. Yen CL, Monetti M, Burri BJ, Farese RV Jr (2005) The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters. J Lipid Res 46:1502–1511

    Article  PubMed  CAS  Google Scholar 

  19. Okuyama H, Lands WE (1972) Variable selectivities of acyl coenzyme A: monoacylglycerophosphate acyltransferases in rat liver. J Biol Chem 247:1414–1423

    PubMed  CAS  Google Scholar 

  20. Yamashita A, Sugiura T, Waku K (1997) Acyltransferases and transacylases involved in fatty acid remodeling of phospholipids and metabolism of bioactive lipids in mammalian cells. J Biochem 122:1–16

    PubMed  CAS  Google Scholar 

  21. Faergeman NJ, Knudsen J (1997) Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling. Biochem J 323(Pt 1):1–12

    PubMed  CAS  Google Scholar 

  22. Larson TR, Graham IA (2001) Technical advance: a novel technique for the sensitive quantification of acyl CoA esters from plant tissues. Plant J 25:115–125

    Article  PubMed  CAS  Google Scholar 

  23. Zaremberg V, McMaster CR (2002) Differential partitioning of lipids metabolized by separate yeast glycerol-3-phosphate acyltransferases reveals that phospholipase D generation of phosphatidic acid mediates sensitivity to choline-containing lysolipids and drugs. J Biol Chem 277:39035–39044

    Article  PubMed  CAS  Google Scholar 

  24. Kuksis A, Breckenridge WC, Marai L, Stachnyk O (1969) Molecular species of lecithins of rat heart, kidney, and plasma. J Lipid Res 10:25–32

    PubMed  CAS  Google Scholar 

  25. Marai L, Kuksis A (1969) Molecular species of lecithins from erythrocytes and plasma of man. J Lipid Res 10:141–152

    PubMed  CAS  Google Scholar 

  26. Wood R, Harlow RD (1969) Structural studies of neutral glycerides and phosphoglycerides of rat liver. Arch Biochem Biophys 131:495–501

    Article  PubMed  CAS  Google Scholar 

  27. Furukawa-Stoffer TL, Boyle RM, Thomson AL, Sarna MA, Weselake RJ (2003) Properties of lysophosphatidylcholine acyltransferase from Brassica napus cultures. Lipids 38:651–656

    Article  PubMed  CAS  Google Scholar 

  28. Waku K, Lands WE (1968) Control of lecithin biosynthesis in erythrocyte membranes. J Lipid Res 9:12–18

    PubMed  CAS  Google Scholar 

  29. Waku K, Lands WE (1968) Acyl coenzyme A:1-alkenyl-glycero-3-phosphorylcholine acyltransferase action in plasmalogen biosynthesis. J Biol Chem 243:2654–2659

    PubMed  CAS  Google Scholar 

  30. Veloso D, Veech RL (1974) Stoichiometric hydrolysis of long chain acyl-CoA and measurement of the CoA formed with an enzymatic cycling method. Anal Biochem 62:449–450

    Article  PubMed  CAS  Google Scholar 

  31. Brecher P The interaction of long-chain acyl CoA with membranes. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6358858, Accessed 1 57

  32. Powell GL, Grothusen JR, Zimmerman JK, Evans CA, Fish WW (1981) A re-examination of some properties of fatty acyl-CoA micelles. J Biol Chem 256:12740–12747

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Dr. Zhifu Zheng and Dr. Olga Kharchenko for helpful discussion and suggestions. We thank Drs. Patrick Covello and Meng Zhang for critical reading of the manuscript. This research is support in part by Genome Prairie and Genome Canada, a not-for-profit organization that is leading Canada’s national strategy on genomics. This is National Research Council Canada publication # 50106.

Author information

Authors and Affiliations

  1. Plant Biotechnology Institute, National Research Council Canada, 110 Gymnasium Place, Saskatoon, SK, S7N OW9, Canada

    Michael Kazachkov, Qilin Chen, Liping Wang & Jitao Zou

  2. Genome Prairie, 101-111 Research Drive, Saskatoon, SK, S7N 3R2, Canada

    Michael Kazachkov

  3. Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Science of Ukraine, 1 Murmanskaya str, Kiev-94, 02660, Ukraine

    Michael Kazachkov

Authors
  1. Michael Kazachkov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qilin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liping Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jitao Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jitao Zou.

About this article

Cite this article

Kazachkov, M., Chen, Q., Wang, L. et al. Substrate Preferences of a Lysophosphatidylcholine Acyltransferase Highlight Its Role in Phospholipid Remodeling. Lipids 43, 895–902 (2008). https://doi.org/10.1007/s11745-008-3233-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-008-3233-y

Keywords

Search

Navigation