Identification of acyl coenzyme A:monoacylglycerol acyltransferase 3, an intestinal specific enzyme implicated in dietary fat absorption.
Acyl coenzyme A:monoacylglycerol acyltransferase (MGAT) catalyzes the synthesis of diacylglycerol using 2-monoacylglycerol and fatty acyl coenzyme A. This enzymatic reaction is believed to be an essential and rate-limiting step for the absorption of fat in the small intestine. Although the first MGAT-encoding cDNA, designated MGAT1, has been recently isolated, it is not expressed in the small intestine and hence cannot account for the high intestinal MGAT enzyme activity that is important for the physiology of fat absorption. In the current study, we report the identification of a novel MGAT, designated MGAT3, and present evidence that it fulfills the criteria to be the elusive intestinal MGAT. MGAT3 encodes a approximately 36-kDa transmembrane protein that is highly homologous to MGAT1 and -2. In humans, expression of MGAT3 is restricted to gastrointestinal tract with the highest level found in the ileum. At the cellular level, recombinant MGAT3 is localized to the endoplasmic reticulum. Recombinant MGAT3 enzyme activity produced in insect Sf9 cells selectively acylates 2-monoacylglycerol with higher efficiency than other stereoisomers. The molecular identification of MGAT3 will facilitate the evaluation of using intestinal MGAT as a potential point of intervention for antiobesity therapies.
Cheng
Dong
D
Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Princeton, New Jersey 08543, USA.
Nelson
Thomas C
TC
Chen
Jian
J
Walker
Stephen G
SG
Wardwell-Swanson
Judith
J
Meegalla
Rupalie
R
Taub
Rebecca
R
Billheimer
Jeffrey T
JT
Ramaker
Michael
M
Feder
John N
JN
D000217:Acyltransferases / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D015256:Coenzyme A-Transferases / Q000737:chemistry* / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D004041:Dietary Fats / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006801:Humans; D007082:Ileum / Q000201:enzymology; D007313:Insecta; D007422:Intestines / Q000201:enzymology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism; D014018:Tissue Distribution
D000596:Amino Acids; D018076:DNA, Complementary; D004041:Dietary Fats; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000217:Acyltransferases; C021802:2-acylglycerol O-acyltransferase; D015256:Coenzyme A-Transferases