Enzymatic activities of the human AGPAT isoform 3 and isoform 5

Localization of AGPAT5 to mitochondria

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The enzyme 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT) converts lysophosphatidic acid (LPA) to phosphatidic acid (PA). In this study, we show enzymatic properties, tissue distribution, and subcellular localization of human AGPAT3 and AGPAT5. In cells overexpressing these isoforms, the proteins were detected in the nuclear envelope and the endoplasmic reticulum. AGPAT5-GFP fusion protein was localized in the mitochondria of both Chinese hamster ovary and human epithelial cervical cancer cells. Using lysates of AD293 cells infected with AGPAT3 and AGPAT5 recombinant adenovirus, we show that AGPAT3 and AGPAT5 proteins have AGPAT activity. Both the isoforms have similar apparent Vmax of 6.35 and 2.42 nmol/ min/mg protein, respectively, for similar LPA. The difference between the two isoforms is in their use of additional lysophospholipids. AGPAT3 shows significant esterification of lysophosphatidylinositol (LPI) in the presence of C20:4 fatty acid, whereas AGPAT5 demonstrates significant acyltransferase activity toward lysophosphatidylethanolamine (LPE) in the presence of C18:1 fatty acid. The AGPAT3 mRNA is ubiquitously expressed in human tissues with several-fold differences in the expression pattern compared with the closely related AGPAT4 . In summary, we show that in the presence of different fatty acids, AGPAT3 and AGPAT5 prefer different lysophospholipids as acyl acceptors. More importantly, localization of overexpressed AGPAT5 (this study) as well as GPAT1 and 2 (previous studies) in mitochondria supports the idea that the mitochondria might be capable of synthesizing some of their own glycerophospholipids. - Prasad, S. S., A. Garg, and A. K. Agarwal. Enzymatic activities of the human AGPAT isoform 3 and isoform 5: localization of AGPAT5 to mitochondria.

Original languageEnglish (US)
Pages (from-to)451-462
Number of pages12
JournalJournal of Lipid Research
Volume52
Issue number3
DOIs
StatePublished - Mar 2011

Fingerprint

1-Acylglycerol-3-Phosphate O-Acyltransferase
Mitochondria
Human Activities
Protein Isoforms
Lysophospholipids
Fatty Acids
Tissue
Glycerophospholipids
Acyltransferases
Phosphatidic Acids
Proteins
Esterification
Nuclear Envelope
Tissue Distribution
Cricetulus
Adenoviridae
Uterine Cervical Neoplasms
Endoplasmic Reticulum
Ovary
Fusion reactions

Keywords

  • 1-acylglycerol-3-phosphate-O-acyltransferase
  • Acyltransferase
  • Lipodystrophy
  • LPAAT
  • Phospholipid

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Enzymatic activities of the human AGPAT isoform 3 and isoform 5 : Localization of AGPAT5 to mitochondria. / Prasad, Sneha S.; Garg, Abhimanyu; Agarwal, Anil K.

In: Journal of Lipid Research, Vol. 52, No. 3, 03.2011, p. 451-462.

Research output: Contribution to journalArticle

@article{979aa16e7bf846189fbc471fe5261824,
title = "Enzymatic activities of the human AGPAT isoform 3 and isoform 5: Localization of AGPAT5 to mitochondria",
abstract = "The enzyme 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT) converts lysophosphatidic acid (LPA) to phosphatidic acid (PA). In this study, we show enzymatic properties, tissue distribution, and subcellular localization of human AGPAT3 and AGPAT5. In cells overexpressing these isoforms, the proteins were detected in the nuclear envelope and the endoplasmic reticulum. AGPAT5-GFP fusion protein was localized in the mitochondria of both Chinese hamster ovary and human epithelial cervical cancer cells. Using lysates of AD293 cells infected with AGPAT3 and AGPAT5 recombinant adenovirus, we show that AGPAT3 and AGPAT5 proteins have AGPAT activity. Both the isoforms have similar apparent Vmax of 6.35 and 2.42 nmol/ min/mg protein, respectively, for similar LPA. The difference between the two isoforms is in their use of additional lysophospholipids. AGPAT3 shows significant esterification of lysophosphatidylinositol (LPI) in the presence of C20:4 fatty acid, whereas AGPAT5 demonstrates significant acyltransferase activity toward lysophosphatidylethanolamine (LPE) in the presence of C18:1 fatty acid. The AGPAT3 mRNA is ubiquitously expressed in human tissues with several-fold differences in the expression pattern compared with the closely related AGPAT4 . In summary, we show that in the presence of different fatty acids, AGPAT3 and AGPAT5 prefer different lysophospholipids as acyl acceptors. More importantly, localization of overexpressed AGPAT5 (this study) as well as GPAT1 and 2 (previous studies) in mitochondria supports the idea that the mitochondria might be capable of synthesizing some of their own glycerophospholipids. - Prasad, S. S., A. Garg, and A. K. Agarwal. Enzymatic activities of the human AGPAT isoform 3 and isoform 5: localization of AGPAT5 to mitochondria.",
keywords = "1-acylglycerol-3-phosphate-O-acyltransferase, Acyltransferase, Lipodystrophy, LPAAT, Phospholipid",
author = "Prasad, {Sneha S.} and Abhimanyu Garg and Agarwal, {Anil K.}",
year = "2011",
month = "3",
doi = "10.1194/jlr.M007575",
language = "English (US)",
volume = "52",
pages = "451--462",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Enzymatic activities of the human AGPAT isoform 3 and isoform 5

T2 - Localization of AGPAT5 to mitochondria

AU - Prasad, Sneha S.

AU - Garg, Abhimanyu

AU - Agarwal, Anil K.

PY - 2011/3

Y1 - 2011/3

N2 - The enzyme 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT) converts lysophosphatidic acid (LPA) to phosphatidic acid (PA). In this study, we show enzymatic properties, tissue distribution, and subcellular localization of human AGPAT3 and AGPAT5. In cells overexpressing these isoforms, the proteins were detected in the nuclear envelope and the endoplasmic reticulum. AGPAT5-GFP fusion protein was localized in the mitochondria of both Chinese hamster ovary and human epithelial cervical cancer cells. Using lysates of AD293 cells infected with AGPAT3 and AGPAT5 recombinant adenovirus, we show that AGPAT3 and AGPAT5 proteins have AGPAT activity. Both the isoforms have similar apparent Vmax of 6.35 and 2.42 nmol/ min/mg protein, respectively, for similar LPA. The difference between the two isoforms is in their use of additional lysophospholipids. AGPAT3 shows significant esterification of lysophosphatidylinositol (LPI) in the presence of C20:4 fatty acid, whereas AGPAT5 demonstrates significant acyltransferase activity toward lysophosphatidylethanolamine (LPE) in the presence of C18:1 fatty acid. The AGPAT3 mRNA is ubiquitously expressed in human tissues with several-fold differences in the expression pattern compared with the closely related AGPAT4 . In summary, we show that in the presence of different fatty acids, AGPAT3 and AGPAT5 prefer different lysophospholipids as acyl acceptors. More importantly, localization of overexpressed AGPAT5 (this study) as well as GPAT1 and 2 (previous studies) in mitochondria supports the idea that the mitochondria might be capable of synthesizing some of their own glycerophospholipids. - Prasad, S. S., A. Garg, and A. K. Agarwal. Enzymatic activities of the human AGPAT isoform 3 and isoform 5: localization of AGPAT5 to mitochondria.

AB - The enzyme 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT) converts lysophosphatidic acid (LPA) to phosphatidic acid (PA). In this study, we show enzymatic properties, tissue distribution, and subcellular localization of human AGPAT3 and AGPAT5. In cells overexpressing these isoforms, the proteins were detected in the nuclear envelope and the endoplasmic reticulum. AGPAT5-GFP fusion protein was localized in the mitochondria of both Chinese hamster ovary and human epithelial cervical cancer cells. Using lysates of AD293 cells infected with AGPAT3 and AGPAT5 recombinant adenovirus, we show that AGPAT3 and AGPAT5 proteins have AGPAT activity. Both the isoforms have similar apparent Vmax of 6.35 and 2.42 nmol/ min/mg protein, respectively, for similar LPA. The difference between the two isoforms is in their use of additional lysophospholipids. AGPAT3 shows significant esterification of lysophosphatidylinositol (LPI) in the presence of C20:4 fatty acid, whereas AGPAT5 demonstrates significant acyltransferase activity toward lysophosphatidylethanolamine (LPE) in the presence of C18:1 fatty acid. The AGPAT3 mRNA is ubiquitously expressed in human tissues with several-fold differences in the expression pattern compared with the closely related AGPAT4 . In summary, we show that in the presence of different fatty acids, AGPAT3 and AGPAT5 prefer different lysophospholipids as acyl acceptors. More importantly, localization of overexpressed AGPAT5 (this study) as well as GPAT1 and 2 (previous studies) in mitochondria supports the idea that the mitochondria might be capable of synthesizing some of their own glycerophospholipids. - Prasad, S. S., A. Garg, and A. K. Agarwal. Enzymatic activities of the human AGPAT isoform 3 and isoform 5: localization of AGPAT5 to mitochondria.

KW - 1-acylglycerol-3-phosphate-O-acyltransferase

KW - Acyltransferase

KW - Lipodystrophy

KW - LPAAT

KW - Phospholipid

UR - http://www.scopus.com/inward/record.url?scp=79953231189&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953231189&partnerID=8YFLogxK

U2 - 10.1194/jlr.M007575

DO - 10.1194/jlr.M007575

M3 - Article

VL - 52

SP - 451

EP - 462

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 3

ER -