FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1994450141> ?p ?o ?g. }

• W1994450141 endingPage "2088" @default.
• W1994450141 startingPage "2079" @default.
• W1994450141 abstract "Glycerol-3-phosphate acyltransferases (GPATs; EC2.3.1.15) catalyze the first step in the de novo synthesis of neutral lipids (triglycerides) and glycerophospholipids. The existence of multiple enzyme isoforms with GPAT activity was predicted many years ago when GPAT activities with distinct kinetic profiles and sensitivity to inhibitors were characterized in two subcellular compartments, mitochondria and microsomes. We now know that mammals have at least four GPAT isoforms with distinct tissue distribution and function. GPAT1 is the major mitochondrial GPAT isoform and is characterized by its resistance to sulfhydryl-modifying reagents, such as N-ethylmaleimide (NEM). GPAT2 is a minor NEM-sensitive mitochondrial isoform. The activity referred to as microsomal GPAT is encoded by two closely related genes, GPAT3 and GPAT4. GPAT isoforms are important regulators of cellular triglyceride and phospholipid content, and may channel fatty acids toward particular metabolic fates. Overexpression and knock-out studies suggest that GPAT isoforms can play important roles in the development of hepatic steatosis, insulin resistance, and obesity; GPAT isoforms are also important for lactation. This review summarizes the current state of knowledge on mammalian GPAT isoforms. Glycerol-3-phosphate acyltransferases (GPATs; EC2.3.1.15) catalyze the first step in the de novo synthesis of neutral lipids (triglycerides) and glycerophospholipids. The existence of multiple enzyme isoforms with GPAT activity was predicted many years ago when GPAT activities with distinct kinetic profiles and sensitivity to inhibitors were characterized in two subcellular compartments, mitochondria and microsomes. We now know that mammals have at least four GPAT isoforms with distinct tissue distribution and function. GPAT1 is the major mitochondrial GPAT isoform and is characterized by its resistance to sulfhydryl-modifying reagents, such as N-ethylmaleimide (NEM). GPAT2 is a minor NEM-sensitive mitochondrial isoform. The activity referred to as microsomal GPAT is encoded by two closely related genes, GPAT3 and GPAT4. GPAT isoforms are important regulators of cellular triglyceride and phospholipid content, and may channel fatty acids toward particular metabolic fates. Overexpression and knock-out studies suggest that GPAT isoforms can play important roles in the development of hepatic steatosis, insulin resistance, and obesity; GPAT isoforms are also important for lactation. This review summarizes the current state of knowledge on mammalian GPAT isoforms. Glycerol-3-phosphate acyltransferases (GPATs; EC2.3.1.15) use glycerol-3-phosphate and fatty acyl-CoA as substrates to catalyze the formation of lysophosphatidic acid, a precursor for phosphatidic acid, which in turn is required for the biosynthesis of both triglycerides and glycerophospholipids (Fig. 1). GPAT activity was first identified in 1953 using guinea pig liver (1Kornberg A. Pricer Jr., W.E. Enzymatic esterification of alpha-glycerophosphate by long chain fatty acids.J. Biol. Chem. 1953; 204: 345-357Abstract Full Text PDF PubMed Google Scholar). It has since been shown that GPAT activity is present in most organisms examined, including vertebrates, invertebrates, plants, fungi, and some bacteria (2Coleman R.A. Lee D.P. Enzymes of triacylglycerol synthesis and their regulation.Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (705) Google Scholar). [It should be noted that many bacterial species utilize the PlsX/Y pathway, which generates lysophosphatidic acid using acyl-phosphate, rather than acyl-CoA or acyl carrier protein, as a substrate (3Zhang Y.M. Rock C.O. Acyltransferases in bacterial glycerophospholipid synthesis.J Lipid Res. 2008; 49: 1867-1874Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar)]. The first gene encoding an enzyme with GPAT activity was cloned from Escherichia coli (E. coli) in 1980 (4Lightner V.A. Bell R.M. Modrich P. The DNA sequences encoding plsBdgk loci of Escherichia coli.J. Biol. Chem. 1983; 258: 10856-10861Abstract Full Text PDF PubMed Google Scholar, 5Lightner V.A. Larson T.J. Tailleur P. Kantor G.D. Raetz C.R. Bell R.M. Modrich P. Membrane phospholipid synthesis in Escherichia coli. Cloning of a structural gene (plsB) of the sn-glycerol-3-phosphate acyl/transferase.J. Biol. Chem. 1980; 255: 9413-9420Abstract Full Text PDF PubMed Google Scholar) and was demonstrated to be an integral membrane protein (PlsB). Mutational analysis of this gene and alignment with several other glycerophospholipid acyltransferases revealed a conserved domain [pfam01553 or COG2937; http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml (6Marchler-Bauer A. Anderson J.B. Derbyshire M.K. DeWeese-Scott C. Gonzales N.R. Gwadz M. Hao L. He S. Hurwitz D.I. Jackson J.D. et al.CDD: a conserved domain database for interactive domain family analysis.Nucleic Acids Res. 2007; 35: D237-D240Crossref PubMed Scopus (693) Google Scholar)] that has since been shown to be present in a large number of acyltransferases, including all mammalian GPAT isoforms identified to date (2Coleman R.A. Lee D.P. Enzymes of triacylglycerol synthesis and their regulation.Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (705) Google Scholar, 7Lewin T.M. Wang P. Coleman R.A. Analysis of amino acid motifs diagnostic for the sn-glycerol-3-phosphate acyltransferase reaction.Biochemistry. 1999; 38: 5764-5771Crossref PubMed Scopus (230) Google Scholar, 8Wilkison W.O. Bell R.M. sn-Glycerol-3-phosphate acyltransferase from Escherichia coli.Biochim. Biophys. Acta. 1997; 1348: 3-9Crossref PubMed Scopus (27) Google Scholar). In mammalian cells, enzymatic studies in the 1960s and 1970s distinguished two GPAT isoforms: a microsomal isoform, which is sensitive to sulfhydryl-modifying reagents, such as N-ethylmaleimide (NEM) and iodoacetamide, and a mitochondrial isoform, which is resistant to NEM (2Coleman R.A. Lee D.P. Enzymes of triacylglycerol synthesis and their regulation.Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (705) Google Scholar, 9Bell R.M. Coleman R.A. Enzymes of glycerolipid synthesis in eukaryotes.Annu. Rev. Biochem. 1980; 49: 459-487Crossref PubMed Scopus (455) Google Scholar). The mitochondrial and microsomal isoforms could also be distinguished by their substrate preference (mitochondrial, NEM-resistant GPAT was shown to prefer saturated fatty acyl-CoA, while microsomal, NEM-sensitive GPAT did not have a preference), and their different sensitivity to temperature, polymixin B, acetone, salts, and chelators (2Coleman R.A. Lee D.P. Enzymes of triacylglycerol synthesis and their regulation.Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (705) Google Scholar, 9Bell R.M. Coleman R.A. Enzymes of glycerolipid synthesis in eukaryotes.Annu. Rev. Biochem. 1980; 49: 459-487Crossref PubMed Scopus (455) Google Scholar). Recent data show that these two enzymatically defined isoforms are in fact encoded by at least four distinct genes, two of which encode mitochondrial isoforms and two of which encode microsomal isoforms (Table 1). In most cells, the GPAT-dependent pathway is thought to be responsible for most of de novo synthesis of neutral lipids and glycerophospholipids. It is important to keep in mind, though, that an alternative pathway for de novo formation of lysophosphatidic acid and ultimately triglycerides and glycerophospholipids also exists (Fig. 1) (10Hajra A.K. Glycerolipid biosynthesis in peroxisomes (microbodies).Prog. Lipid Res. 1995; 34: 343-364Crossref PubMed Scopus (67) Google Scholar). This pathway, localized in peroxisomes, uses dihydroxyacetone phosphate to generate 1-acyl-dihydroxyacetone phosphate, which in turn is reduced by 1-acyl-dihydroxyacetone phosphate reductase to lysophosphatidic acid (10Hajra A.K. Glycerolipid biosynthesis in peroxisomes (microbodies).Prog. Lipid Res. 1995; 34: 343-364Crossref PubMed Scopus (67) Google Scholar). This pathway is thought to be of only minor quantitative importance for the formation of triglycerides and glycerophospholipids in most tissues, and functions primarily in the formation of ether phospholipids, as demonstrated by studies in tissue culture cells as well as by mutational analysis in mice and humans (11Rodemer C. Thai T.P. Brugger B. Kaercher T. Werner H. Nave K.A. Wieland F. Gorgas K. Just W.W. Inactivation of ether lipid biosynthesis causes male infertility, defects in eye development and optic nerve hypoplasia in mice.Hum. Mol. Genet. 2003; 12: 1881-1895Crossref PubMed Scopus (173) Google Scholar, 12Gorgas K. Teigler A. Komljenovic D. Just W.W. The ether lipid-deficient mouse: tracking down plasmalogen functions.Biochim. Biophys. Acta. 2006; 1763: 1511-1526Crossref PubMed Scopus (182) Google Scholar, 13Liu D. Nagan N. Just W.W. Rodemer C. Thai T-P. Zoeller R.A. Role of dihydroxyacetonephosphate acyltransferase in the biosynthesis of plasmalogens and nonether glycerolipids.J. Lipid Res. 2005; 46: 727-735Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 14Ofman R. Hettema E.H. Hogenhout E.M. Caruso U. Muijsers A.O. Wanders R.J. Acyl-CoA:dihydroxyacetonephosphate acyltransferase: cloning of the human cDNA and resolution of the molecular basis in rhizomelic chondrodysplasia punctata type 2.Hum. Mol. Genet. 1998; 7: 847-853Crossref PubMed Scopus (99) Google Scholar, 15Declercq P.E. Haagsman H.P. Van Veldhoven P. Debeer L.J. Van Golde L.M. Mannaerts G.P. Rat liver dihydroxyacetone-phosphate acyltransferases and their contribution to glycerolipid synthesis.J. Biol. Chem. 1984; 259: 9064-9075Abstract Full Text PDF PubMed Google Scholar). However, it can contribute significantly to glycerolipid formation under certain circumstances (e.g., in differentiated 3T3-L1 adipocytes after an overnight culture in glucose-free medium) (16Hajra A.K. Larkins L.K. Das A.K. Hemati N. Erickson R.L. MacDougald O.A. Induction of the peroxisomal glycerolipid-synthesizing enzymes during differentiation of 3T3–L1 adipocytes. Role in triacylglycerol synthesis.J. Biol. Chem. 2000; 275: 9441-9446Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar). It is also noteworthy that diacylglycerol can be produced via the monoacylglycerol pathway in a GPAT-independent manner. The monoacylglycerol pathway utilizes 2-monoacylglycerol and fatty acyl-CoA to generate diacylglycerol (17Lehner R. Kuksis A. Biosynthesis of triacylglycerols.Prog. Lipid Res. 1996; 35: 169-201Crossref PubMed Scopus (254) Google Scholar). In enterocytes, this pathway constitutes a major route for triglyceride formation during fat absorption.Table 1Genes encoding mammalian GPAT isoformsGene NameAliasSubcellular LocalizationSensitivity to NEMAccession NumberReferenceGPAT1mtGPAT1, GPAMMitochondriaResistantNM_020918 (h)NM_008149 (m)(31Yet S.F. Lee S. Young Tae H. Hei Sook S. Expression and identification of p90 as the murine mitochondrial glycerol- 3-phosphate acyltransferase.Biochemistry. 1993; 32: 9486-9491Crossref PubMed Scopus (77) Google Scholar)NM_017274 (r)GPAT2mtGPAT2, xGPAT1MitochondriaSensitiveNM_207328 (h)(68Wang S. Lee D.P. Gong N. Schwerbrock N.M. Mashek D.G. Gonzalez-Baro M.R. Stapleton C. Li L.O. Lewin T.M. Coleman R.A. Cloning and functional characterization of a novel mitochondrial N-ethylmaleimide-sensitive glycerol-3-phosphate acyltransferase (GPAT2).Arch. Biochem. Biophys. 2007; 465: 347-358Crossref PubMed Scopus (67) Google Scholar,69Harada N. Hara S. Yoshida M. Zenitani T. Mawatari K. Nakano M. Takahashi A. Hosaka T. Yoshimoto K. Nakaya Y. Molecular cloning of a murine glycerol-3-phosphate acyltransferase-like protein 1 (xGPAT1).Mol. Cell. Biochem. 2007; 297: 41-51Crossref PubMed Scopus (29) Google Scholar)NM_001081089 (m)XM_238283 (r)GPAT3AGPAT8,aThe names AGPAT8 (86) and AGPAT9 (87) have also been used for the unrelated genes LYCAT (NM_001002257) (88) and LPCAT1 (NM_024830) (89). AGPAT9,aThe names AGPAT8 (86) and AGPAT9 (87) have also been used for the unrelated genes LYCAT (NM_001002257) (88) and LPCAT1 (NM_024830) (89). LPAAT-thetaEndoplasmic reticulumSensitiveNM_032717 (h)(53Cao J. Li J.L. Li D. Tobin J.F. Gimeno R.E. Molecular identification of microsomal acyl-CoA:glycerol-3-phosphate acyltransferase, a key enzyme in de novo triacylglycerol synthesis.Proc. Natl. Acad. Sci. USA. 2006; 103: 19695-19700Crossref PubMed Scopus (162) Google Scholar,81Tang W. Yuan J. Chen X. Gu X. Luo K. Li J. Wan B. Wang Y. Yu L. Identification of a novel human lysophosphatidic acid acyltransferase, LPAAT-theta, which activates mTOR pathway.J. Biochem. Mol. Biol. 2006; 39: 626-635Crossref PubMed Google Scholar)NM_172715 (m)NM_001025670 (r)GPAT4AGPAT6, LPAAT-zetaEndoplasmic reticulumSensitiveNM_178819 (h)(71Nagle C.A. Vergnes L. Dejong H. Wang S. Lewin T.M. Reue K. Coleman R.A. Identification of a novel sn-glycerol-3-phosphate acyltransferase isoform, GPAT4, as the enzyme deficient in Agpat6−/− mice.J. Lipid Res. 2008; 49: 823-831Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar, 72Chen Y.Q. Kuo M.S. Li S. Bui H.H. Peake D.A. Sanders P.E. Thibodeaux S.J. Chu S. Qian Y.W. Zhao Y. et al.AGPAT6 is a novel microsomal glycerol-3-phosphate acyltransferase.J. Biol. Chem. 2008; 283: 10048-10057Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar, 73Beigneux A.P. Vergnes L. Qiao X. Quatela S. Davis R. Watkins S.M. Coleman R.A. Walzem R.L. Philips M. Reue K. et al.Agpat6–a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium.J. Lipid Res. 2006; 47: 734-744Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 74Vergnes L. Beigneux A.P. Davis R. Watkins S.M. Young S.G. Reue K. Agpat6 deficiency causes subdermal lipodystrophy and resistance to obesity.J. Lipid Res. 2006; 47: 745-754Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar,85Li D. Yu L. Wu H. Shan Y. Guo J. Dang Y. Wei Y. Zhao S. Cloning and identification of the human LPAAT-zeta gene, a novel member of the lysophosphatidic acid acyltransferase family.J. Hum. Genet. 2003; 48: 438-442Crossref PubMed Scopus (39) Google Scholar)NM_018743 (m)NM_001047849 (r)LPAAT, lysophosphatidic acid acyltransferases. Mammalian GPAT isoforms identified at the molecular level to date are shown. The gene names listed in column one represents the nomenclature used most recently in the literature. Alternative names are shown in column 2. Accession numbers were assigned based on references cited and on our unpublished sequence analysis.a The names AGPAT8 (86Agarwal A.K. Barnes R.I. Garg A. Functional characterization of human 1-acylglycerol-3-phosphate acyltransferase isoform 8: cloning, tissue distribution, gene structure, and enzymatic activity.Arch. Biochem. Biophys. 2006; 449: 64-76Crossref PubMed Scopus (52) Google Scholar) and AGPAT9 (87Agarwal A.K. Sukumaran S. Bartz R. Barnes R.I. Garg A. Functional characterization of human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 9: cloning, tissue distribution, gene structure, and enzymatic activity.J. Endocrinol. 2007; 193: 445-457Crossref PubMed Scopus (39) Google Scholar) have also been used for the unrelated genes LYCAT (NM_001002257) (88Cao J. Liu Y. Lockwood J. Burn P. Shi Y. A novel cardiolipin-remodeling pathway revealed by a gene encoding an endoplasmic reticulum-associated acyl-CoA:lysocardiolipin acyltransferase (ALCAT1) in mouse.J. Biol. Chem. 2004; 279: 31727-31734Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar) and LPCAT1 (NM_024830) (89Nakanishi H. Shindou H. Hishikawa D. Harayama T. Ogasawara R. Suwabe A. Taguchi R. Shimizu T. 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. 2006; 281: 20140-20147Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar). Open table in a new tab LPAAT, lysophosphatidic acid acyltransferases. Mammalian GPAT isoforms identified at the molecular level to date are shown. The gene names listed in column one represents the nomenclature used most recently in the literature. Alternative names are shown in column 2. Accession numbers were assigned based on references cited and on our unpublished sequence analysis. Recent interest in GPATs has been fueled by the recognition that mutations in genes encoding enzymes in the glycerolipid biosynthetic pathway can contribute to or modulate human disease, and that small molecules that inhibit these enzymes may be beneficial for the treatment of disease. For example, genes encoding enzymes in the triglyceride biosynthetic pathway have been shown to be mutated in human and mouse lipodystrophy syndromes (LPIN1, AGPAT2) (18Agarwal A.K. Garg A. Congenital generalized lipodystrophy: significance of triglyceride biosynthetic pathways.Trends Endocrinol. Metab. 2003; 14: 214-221Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar, 19Reue K. Zhang P. The lipin protein family: dual roles in lipid biosynthesis and gene expression.FEBS Lett. 2008; 582: 90-96Crossref PubMed Scopus (161) Google Scholar), and polymorphisms in both LPIN1 and LPIN2 genes have been linked to body weight and insulin sensitivity (20Reue K. Donkor J. Genetic factors in type 2 diabetes: all in the (lipin) family.Diabetes. 2007; 56: 2842-2843Crossref PubMed Scopus (12) Google Scholar). Genes encoding enzymes in the triglyceride biosynthetic pathway have also been linked to inflammatory disorders (LPIN2, AGPAT2) (21Ferguson P.J. Chen S. Tayeh M.K. Ochoa L. Leal S.M. Pelet A. Munnich A. Lyonnet S. Majeed H.A. El-Shanti H. Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome).J. Med. Genet. 2005; 42: 551-557Crossref PubMed Scopus (309) Google Scholar, 22Leung D.W. The structure and functions of human lysophosphatidic acid acyltransferases.Front. Biosci. 2001; 6: D944-D953Crossref PubMed Google Scholar) and survival of certain cancers (AGPAT2) (23Diefenbach C.S. Soslow R.A. Iasonos A. Linkov I. Hedvat C. Bonham L. Singer J. Barakat R.R. Aghajanian C. Dupont J. Lysophosphatidic acid acyltransferase-beta (LPAAT-beta) is highly expressed in advanced ovarian cancer and is associated with aggressive histology and poor survival.Cancer. 2006; 107: 1511-1519Crossref PubMed Scopus (34) Google Scholar, 24La Rosee P. Jia T. Demehri S. Hartel N. de Vries P. Bonham L. Hollenback D. Singer J.W. Melo J.V. Druker B.J. et al.Antileukemic activity of lysophosphatidic acid acyltransferase-beta inhibitor CT32228 in chronic myelogenous leukemia sensitive and resistant to imatinib.Clin. Cancer Res. 2006; 12: 6540-6546Crossref PubMed Scopus (22) Google Scholar). Since deletion (25Chen H.C. Farese Jr., R.V. Inhibition of triglyceride synthesis as a treatment strategy for obesity: lessons from DGAT1-deficient mice.Arterioscler. Thromb. Vasc. Biol. 2005; 25: 482-486Crossref PubMed Scopus (132) Google Scholar) or inhibition (26Zhao G. Souers A.J. Voorbach M. Falls H.D. Droz B. Brodjian S. Lau Y.Y. Iyengar R.R. Gao J. Judd A.S. et al.Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor.J. Med. Chem. 2008; 51: 380-383Crossref PubMed Scopus (119) Google Scholar) of diacylglycerol acyltransferase 1 (DGAT1) in mouse decreases body weight and improves insulin resistance, there has been intense interest in the development of DGAT1 inhibitors for the treatment of obesity and type 2 diabetes. It might be expected that GPAT isoforms also play a role in human disease and/or could be targets for therapeutics. Consistent with this prediction, knock-outs of two GPAT isoforms in mice, GPAT1 and GPAT4 lead to significant alterations in body weight, insulin sensitivity, and other physiological processes (described in detail below). Since the information on the recently cloned GPAT isoforms is still limited, it is useful to review the body of literature examining the properties of GPAT isoforms in different tissues, using enzymatic studies. These studies found that the mitochondrial isoform accounts for ∼50% of total GPAT activity in rat liver and is significantly decreased upon fasting (27Nimmo H.G. Evidence for the existence of isoenzymes of glycerol phosphate acyltransferase.Biochem. J. 1979; 177: 283-288Crossref PubMed Scopus (28) Google Scholar, 28Bates E.J. Saggerson E.D. A study of the glycerol phosphate acyltransferase and dihydroxyacetone phosphate acyltransferase activities in rat liver mitochondrial and microsomal fractions. Relative distribution in parenchymal and non-parenchymal cells, effects of N-ethylmaleimide, palmitoyl-coenzyme A concentration, starvation, adrenalectomy and anti-insulin serum treatment.Biochem. J. 1979; 182: 751-762Crossref PubMed Scopus (74) Google Scholar). The microsomal isoform is the major isoform in brown and white adipose tissue, accounting for 80–90% of total GPAT activity (29Saggerson E.D. Carpenter C.A. Cheng C.H. Sooranna S.R. Subcellular distribution and some properties of N-ethylmaleimide-sensitive and-insensitive forms of glycerol phosphate acyltransferase in rat adipocytes.Biochem. J. 1980; 190: 183-189Crossref PubMed Scopus (29) Google Scholar, 30Baht H.S. Saggerson E.D. Comparison of triacylglycerol synthesis in rat brown and white adipocytes. Effects of hypothyroidism and streptozotocin-diabetes on enzyme activities and metabolic fluxes.Biochem. J. 1988; 250: 325-333Crossref PubMed Scopus (22) Google Scholar), and is dramatically upregulated during adipocyte differentiation (16Hajra A.K. Larkins L.K. Das A.K. Hemati N. Erickson R.L. MacDougald O.A. Induction of the peroxisomal glycerolipid-synthesizing enzymes during differentiation of 3T3–L1 adipocytes. Role in triacylglycerol synthesis.J. Biol. Chem. 2000; 275: 9441-9446Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar, 31Yet S.F. Lee S. Young Tae H. Hei Sook S. Expression and identification of p90 as the murine mitochondrial glycerol- 3-phosphate acyltransferase.Biochemistry. 1993; 32: 9486-9491Crossref PubMed Scopus (77) Google Scholar, 32Coleman R.A. Reed B.C. Mackall J.C. Student A.K. Lane M.D. Bell R.M. Selective changes in microsomal enzymes of triacylglycerol phosphatidylcholine, and phosphatidylethanolamine biosynthesis during differentiation of 3T3–L1 preadipocytes.J. Biol. Chem. 1978; 253: 7256-7261Abstract Full Text PDF PubMed Google Scholar). Microsomal GPAT is also the major isoform in heart (∼70% of total activity) (33Swanton E.M. Saggerson E.D. Glycerolipid metabolizing enzymes in rat ventricle and in cardiac myocytes.Biochim. Biophys. Acta. 1997; 1346: 93-102Crossref PubMed Scopus (22) Google Scholar, 34Lewin T.M. de Jong H. Schwerbrock N.J. Hammond L.E. Watkins S.M. Combs T.P. Coleman R.A. Mice deficient in mitochondrial glycerol-3-phosphate acyltransferase-1 have diminished myocardial triacylglycerol accumulation during lipogenic diet and altered phospholipid fatty acid composition.Biochim Biophys Acta. 2008; 1781: 352-358Crossref PubMed Scopus (47) Google Scholar), and in brain (35Fitzpatrick S.M. Sorresso G. Haldar D. Acyl-CoA: sn-glycerol-3-phosphate O-acyltransferase in rat brain mitochondria and microsomes.J. Neurochem. 1982; 39: 286-289Crossref PubMed Scopus (11) Google Scholar). In skeletal muscle, in contrast, it has been reported that >90% of total GPAT activity is the mitochondrial, NEM-resistant isoform (36Park H. Kaushik V.K. Constant S. Prentki M. Przybytkowski E. Ruderman N.B. Saha A.K. Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise.J. Biol. Chem. 2002; 277: 32571-32577Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar). Total GPAT activity was reported to be dramatically (∼5-fold) upregulated in the islets of obese rats; however, the contribution of different GPAT isoforms to total GPAT activity in islets has not yet been determined (37Lee Y. Hirose H. Zhou Y.T. Esser V. McGarry J.D. Unger R.H. Increased lipogenic capacity of the islets of obese rats: a role in the pathogenesis of NIDDM.Diabetes. 1997; 46: 408-413Crossref PubMed Scopus (175) Google Scholar). Mitochondrial and microsomal activites are often but not always regulated differentially. Exercise leads to a significant decrease in mitochondrial, but not microsomal GPAT activity in the liver and adipose tissue (36Park H. Kaushik V.K. Constant S. Prentki M. Przybytkowski E. Ruderman N.B. Saha A.K. Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise.J. Biol. Chem. 2002; 277: 32571-32577Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar). In rat white adipose tissue, long-term starvation caused a decrease in the activity of mitochondrial, but not microsomal GPAT activity (38Lawson N. Pollard A.D. Jennings R.J. Gurr M.I. Brindley D.N. The activities of lipoprotein lipase and of enzymes involved in triacylglycerol synthesis in rat adipose tissue. Effects of starvation, dietary modification and of corticotropin injection.Biochem. J. 1981; 200: 285-294Crossref PubMed Scopus (26) Google Scholar). Similarly, starvation or AMP-dependent kinase activation decreases hepatic mitochondrial but not microsomal GPAT activity (28Bates E.J. Saggerson E.D. A study of the glycerol phosphate acyltransferase and dihydroxyacetone phosphate acyltransferase activities in rat liver mitochondrial and microsomal fractions. Relative distribution in parenchymal and non-parenchymal cells, effects of N-ethylmaleimide, palmitoyl-coenzyme A concentration, starvation, adrenalectomy and anti-insulin serum treatment.Biochem. J. 1979; 182: 751-762Crossref PubMed Scopus (74) Google Scholar, 39Muoio D.M. Seefeld K. Witters L.A. Coleman R.A. AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target.Biochem. J. 1999; 338: 783-791Crossref PubMed Scopus (344) Google Scholar). In contrast, both mitochondrial and microsomal GPAT activities are increased in the liver of diet-induced or genetically obese mice (40Linden D. William-Olsson L. Rhedin M. Asztely A.K. Clapham J.C. Schreyer S. Overexpression of mitochondrial GPAT in rat hepatocytes leads to decreased fatty acid oxidation and increased glycerolipid biosynthesis.J. Lipid Res. 2004; 45: 1279-1288Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar). In cold-exposed rats, mitochondrial and, to a lesser extent, microsomal GPAT activity is upregulated in brown adipose tissue (41Darnley A.C. Carpenter C.A. Saggerson E.D. Changes in activities of some enzymes of glycerolipid synthesis in brown adipose tissue of cold-acclimated rats.Biochem. J. 1988; 253: 351-355Crossref PubMed Scopus (18) Google Scholar, 42Mitchell J.R.D. Saggerson E.D. Activities of enzymes of glycerolipid synthesis in brown adipose tissue after treatment of rats with the adrenergic agonists BRL 26830A and phenylephrine, after exposure to cold and in streptozotocin-diabetes.Biochem. J. 1991; 277: 665-669Crossref PubMed Scopus (5) Google Scholar, 43Mitchell J.R.D. Saggerson E.D. The response of brown adipose tissue mitochondrial glycerolphosphate acyltransferase to cold-exposure in hypothyroidism, after adrenalectomy and after treatment with cycloheximide.Int. J. Biochem. 1994; 26: 67-72Crossref PubMed Scopus (1) Google Scholar). Increases in microsomal GPAT activity have also been reported in adipose tissue and small intestine of obese rats compared with lean controls (44Jamdar S.C. Cao W.F. Triacylglycerol biosynthetic enzymes in lean and obese Zucker rats.Biochimica et Biophysica Acta - Lipids and Lipid Metabolism. 1995; 1255: 237-243Crossref PubMed Scopus (27) Google Scholar). While hypothyroidism leads to an increase in microsomal and a decrease in mitochondrial GPAT activity in brown and white adipose tissue, streptozotocin-induced diabetes decreases both activities (30Baht H.S. Saggerson E.D. Comparison of triacylglycerol synthesis in rat brown and white adipocytes. Effects of hypothyroidism and streptozotocin-diabetes on enzyme activities and metabolic fluxes.Biochem. J. 1988; 250: 325-333Crossref PubMed Scopus (22) Google Scholar, 42Mitchell J.R.D. Saggerson E.D. Activities of enzymes of glycerolipid synthesis in brown adipose tissue after treatment of rats with the adrenergic agonists BRL 26830A and phenylephrine, after exposure to cold and in streptozotocin-diabetes.Biochem. J. 1991; 277: 665-669Crossref PubMed Scopus (5) Google Scholar, 43Mitchell J.R.D. Saggerson E.D. The response of brown adipose tissue mitochondrial glycerolphosphate acyltransferase to cold-exposure in hypothyroidism, after adrenalectomy and after treatment with cycloheximide.Int. J. Biochem. 1994; 26: 67-72Crossref PubMed Scopus (1) Google Scholar). Mitochondrial NEM-resistant GPAT (GPAT1) was the first mammalian GPAT isoform to be cloned. In an attempt to identify genes induced in livers of fasted mice refed a high-carbohydrate diet, Sul et al. (45Paulauskis J.D. Sul H.S. Cloning and expression of mouse fatty acid synthase and other specific mRNAs. Developmental and hormonal regulation in 3T3–L1 cells.J. Biol. Chem. 1988; 263: 7049-7054Abstract Full Text PDF PubMed Google Scholar, 46Shin D.H. Paulauskis J.D. Moustaid N. Sul H.S. Transcriptional regulation of p90 with sequence homology to Escherichia coli glycerol-3-phosphate acyltransferase.J. Biol. Chem. 1991; 266: 23834-23839Abstract Full Text PDF PubMed Google Scholar) identified a 6.8 kb mRNA encoding a protein with molecular mas" @default.
• W1994450141 created "2016-06-24" @default.
• W1994450141 creator A5022123972 @default.
• W1994450141 creator A5064772594 @default.
• W1994450141 date "2008-10-01" @default.
• W1994450141 modified "2023-10-14" @default.
• W1994450141 title "Thematic Review Series: Glycerolipids. Mammalian glycerol-3-phosphate acyltransferases: new genes for an old activity" @default.
• W1994450141 cites W1481366545 @default.
• W1994450141 cites W1501515880 @default.
• W1994450141 cites W1507165607 @default.
• W1994450141 cites W1509570939 @default.
• W1994450141 cites W1514989466 @default.
• W1994450141 cites W1524585962 @default.
• W1994450141 cites W1535781736 @default.
• W1994450141 cites W1569331386 @default.
• W1994450141 cites W1574063311 @default.
• W1994450141 cites W1823256410 @default.
• W1994450141 cites W1974083452 @default.
• W1994450141 cites W1975777149 @default.
• W1994450141 cites W1979156768 @default.
• W1994450141 cites W1982268890 @default.
• W1994450141 cites W1982404045 @default.
• W1994450141 cites W1987233412 @default.
• W1994450141 cites W1992952698 @default.
• W1994450141 cites W1995784606 @default.
• W1994450141 cites W1999153099 @default.
• W1994450141 cites W1999169071 @default.
• W1994450141 cites W2000395184 @default.
• W1994450141 cites W2006375647 @default.
• W1994450141 cites W2010363699 @default.
• W1994450141 cites W2010988196 @default.
• W1994450141 cites W2013640969 @default.
• W1994450141 cites W2016299600 @default.
• W1994450141 cites W2017061507 @default.
• W1994450141 cites W2018915186 @default.
• W1994450141 cites W2021657723 @default.
• W1994450141 cites W2026342383 @default.
• W1994450141 cites W2035187068 @default.
• W1994450141 cites W2037792818 @default.
• W1994450141 cites W2041124952 @default.
• W1994450141 cites W2044483591 @default.
• W1994450141 cites W2045132965 @default.
• W1994450141 cites W2053816646 @default.
• W1994450141 cites W2055837207 @default.
• W1994450141 cites W2057283589 @default.
• W1994450141 cites W2057346398 @default.
• W1994450141 cites W2058869575 @default.
• W1994450141 cites W2059056921 @default.
• W1994450141 cites W2060503560 @default.
• W1994450141 cites W2062005522 @default.
• W1994450141 cites W2072462285 @default.
• W1994450141 cites W2075006085 @default.
• W1994450141 cites W2075734349 @default.
• W1994450141 cites W2076713785 @default.
• W1994450141 cites W2077256608 @default.
• W1994450141 cites W2078249110 @default.
• W1994450141 cites W2085410127 @default.
• W1994450141 cites W2086853859 @default.
• W1994450141 cites W2086975308 @default.
• W1994450141 cites W2090182010 @default.
• W1994450141 cites W2096234478 @default.
• W1994450141 cites W2102394855 @default.
• W1994450141 cites W2104625557 @default.
• W1994450141 cites W2106213860 @default.
• W1994450141 cites W2107506498 @default.
• W1994450141 cites W2111410004 @default.
• W1994450141 cites W2113961541 @default.
• W1994450141 cites W2116023336 @default.
• W1994450141 cites W2124753768 @default.
• W1994450141 cites W2128076901 @default.
• W1994450141 cites W2130813720 @default.
• W1994450141 cites W2132611682 @default.
• W1994450141 cites W2134016419 @default.
• W1994450141 cites W2136472893 @default.
• W1994450141 cites W2140230838 @default.
• W1994450141 cites W2143093961 @default.
• W1994450141 cites W2144165835 @default.
• W1994450141 cites W2158795732 @default.
• W1994450141 cites W2160256928 @default.
• W1994450141 cites W2161905497 @default.
• W1994450141 cites W2162089651 @default.
• W1994450141 cites W2164942645 @default.
• W1994450141 cites W2165229113 @default.
• W1994450141 cites W2167519336 @default.
• W1994450141 cites W2168600251 @default.
• W1994450141 cites W2172145321 @default.
• W1994450141 cites W2211307203 @default.
• W1994450141 cites W2236046215 @default.
• W1994450141 cites W2323983892 @default.
• W1994450141 cites W2326549699 @default.
• W1994450141 cites W2336279850 @default.
• W1994450141 cites W38541217 @default.
• W1994450141 cites W4231733340 @default.
• W1994450141 cites W55029422 @default.
• W1994450141 cites W6561245 @default.
• W1994450141 doi "https://doi.org/10.1194/jlr.r800013-jlr200" @default.
• W1994450141 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18658143" @default.
• W1994450141 hasPublicationYear "2008" @default.

• next