Functional characterization of human 1-acylglycerol-3-phosphate acyltransferase isoform 8: cloning, tissue distribution, gene structure, and enzymatic activity

Archives of Biochemistry and Biophysics
Anil K AgarwalAbhimanyu Garg

Abstract

Glycerophospholipids and triglycerides are synthesized de novo by cells through an evolutionary conserved process involving serial acylations of phosphorylated glycerol. Various isoforms of the enzyme, 1-acylglycerol-3-phosphate acyltransferase (AGPAT), acylate lysophosphatidic acid at the sn-2 position to produce phosphatidic acid. We cloned a cDNA predicted to be AGPAT isoform and designated it AGPAT8. Human and mouse AGPAT8 proteins are 89% homologous, and their gene structure is also highly conserved. AGPAT8 is most closely related to AGPAT5, and its cDNA is expressed most in the heart, while AGPAT5 is expressed more in the prostate and testis. In cell lysates, AGPAT8 shows moderate acyltransferase activity with [(3)H]oleoyl-CoA but lacks acyl-CoA:lysocardiolipin acyltransferase activity. In whole cells upon incubation with [(14)C]linoleic acid, most of the radioactivity was recovered in phosphatidyl ethanolamine, phosphatidyl choline and phosphatidic acid fraction. Of the two well conserved acyltransferase motifs, NHX(4)D is present in AGPAT8, whereas arginine in the EGTR motif is substituted by aspartate. However, mutation of EGTD to EGTR did not increase enzymatic activity significantly. Based on the X-ray crystallograph...Continue Reading

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Citations

Jun 2, 2011·Chemical Reviews·Rosalind A Coleman, Douglas G Mashek
Dec 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Eric SoupeneFrans A Kuypers
May 26, 2006·Annual Review of Genomics and Human Genetics·Anil K Agarwal, Abhimanyu Garg
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Apr 1, 2007·Future Lipidology·Maryam AhmadianHei Sook Sul
Nov 22, 2014·Biology·Atsushi YamashitaTakayuki Sugiura
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Aug 23, 2008·The Journal of Biological Chemistry·Hideo Shindou, Takao Shimizu
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Aug 2, 2017·The Journal of International Medical Research·Bo HouChunbo Wang

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