Objective To identify the active compounds from the barks of Betula platyphylla for inhibitory on diacylglycerol acyltransferase（DGAT1）.Methods Bioassay-guided fractionation resulted in the isolation of DGAT1 inhibi...Objective To identify the active compounds from the barks of Betula platyphylla for inhibitory on diacylglycerol acyltransferase（DGAT1）.Methods Bioassay-guided fractionation resulted in the isolation of DGAT1 inhibitory activity of lupane triterpenes.Results Ten compounds were identified as lupenone（1）,lupeol（2）,betulinic acid（3）,betulinaldehyde（4）,betulin（5）,3-deoxybetulonic acid（6）,glochidonol（7）,lup-20/29-ene-1β/3β-diol（8）,3α-hydroxy-lup-20（29）-en-23,28-dioic acid（9）,and 3α,11α-dihydroxy-23-oxo-lup-20（29）-en-28-oic acid（10）.Compounds 3-6,9,and 10 inhibited DGAT1 with IC50 values ranging from（11.2±0.3）to（38.6±1.2）μmol/L.Conclusion Compounds 6,9,and 10 are first isolated from the barks of B.platyphylla.,and compounds 3-6,9,and 10 from the barks of B.platyphylla are responsible for the inhibition on DGAT1.展开更多
Two cDNAs encoding putative type 1 acyl-CoA： diacylglycerol acyltransferases （DGAT1, EC 2.3.1.20）, were cloned from Tetraena mongolica Maxim., an extreme xerophyte with high oil content in the stems. The 1,488-bp a...Two cDNAs encoding putative type 1 acyl-CoA： diacylglycerol acyltransferases （DGAT1, EC 2.3.1.20）, were cloned from Tetraena mongolica Maxim., an extreme xerophyte with high oil content in the stems. The 1,488-bp and 1,485-bp of the open reading frame （ORF） of the two cDNAs, designated as TmDGAT1a and TmDGAT1b, were both predicted to encode proteins of 495 and 494 amino acids, respectively. Southern blot analysis revealed that TmDGAT1a and TmDGAT1b both had low copy numbers in the T. mongolica genome. In addition to ubiquitous expression with different intensity in different tissues, including stems, leaves and roots, TmDGAT1a and TmDGAT1b, were found to be strongly induced by high salinity, drought and osmotic stress, resulting in a remarkable increase of triacylglycerol （TAG） accumulation in T. mongolica plantlets. TmDGAT1a and TmDGAT1b activities were confirmed in the yeast H1246 quadruple mutant （DGA1, LRO1, ARE1, ARE2） by restoring DGAT activity of the mutant host to produce TAG. Overexpression of TmDGAT1a and TmDGAT1b in soybean hairy roots as well as in T. mongolica calli both resulted in an increase in oil content （ranging from 37% to 108%）, accompanied by altered fatty acid profiles.展开更多
The enzymes of the acyl-coenzyme A:cholesterol acyltransferase(ACAT)family are responsible for the in vivo synthesis of neutral lipids.They are potential drug targets for the intervention of atherosclerosis,hyperlipid...The enzymes of the acyl-coenzyme A:cholesterol acyltransferase(ACAT)family are responsible for the in vivo synthesis of neutral lipids.They are potential drug targets for the intervention of atherosclerosis,hyperlipidemia,obesity,type II diabetes and even Alzheimer’s disease.ACAT family enzymes are integral endoplasmic reticulum(ER)membrane proteins and can be divided into ACAT branch and acyl-coenzyme A:diacylglycerol acyltransferase 1(DGAT1)branch according to their substrate specificity.The ACAT branch catalyzes synthesis of cholesteryl esters using long-chain fatty acyl-coenzyme A and cholesterol as substrates,while the DGAT1 branch catalyzes synthesis of triacylglycerols using fatty acylcoenzyme A and diacylglycerol as substrates.In this review,we mainly focus on the recent progress in the structural research of ACAT family enzymes,including their disulfide linkage,membrane topology,subunit interaction and catalysis mechanism.展开更多
基金Science and Technology Development Program of Jilin Province(201205099)
文摘Objective To identify the active compounds from the barks of Betula platyphylla for inhibitory on diacylglycerol acyltransferase（DGAT1）.Methods Bioassay-guided fractionation resulted in the isolation of DGAT1 inhibitory activity of lupane triterpenes.Results Ten compounds were identified as lupenone（1）,lupeol（2）,betulinic acid（3）,betulinaldehyde（4）,betulin（5）,3-deoxybetulonic acid（6）,glochidonol（7）,lup-20/29-ene-1β/3β-diol（8）,3α-hydroxy-lup-20（29）-en-23,28-dioic acid（9）,and 3α,11α-dihydroxy-23-oxo-lup-20（29）-en-28-oic acid（10）.Compounds 3-6,9,and 10 inhibited DGAT1 with IC50 values ranging from（11.2±0.3）to（38.6±1.2）μmol/L.Conclusion Compounds 6,9,and 10 are first isolated from the barks of B.platyphylla.,and compounds 3-6,9,and 10 from the barks of B.platyphylla are responsible for the inhibition on DGAT1.
基金supported by the National Natural Science Foundation of China (30770224)the National Basic Research Program of China (2011CBA00901)
文摘Two cDNAs encoding putative type 1 acyl-CoA： diacylglycerol acyltransferases （DGAT1, EC 2.3.1.20）, were cloned from Tetraena mongolica Maxim., an extreme xerophyte with high oil content in the stems. The 1,488-bp and 1,485-bp of the open reading frame （ORF） of the two cDNAs, designated as TmDGAT1a and TmDGAT1b, were both predicted to encode proteins of 495 and 494 amino acids, respectively. Southern blot analysis revealed that TmDGAT1a and TmDGAT1b both had low copy numbers in the T. mongolica genome. In addition to ubiquitous expression with different intensity in different tissues, including stems, leaves and roots, TmDGAT1a and TmDGAT1b, were found to be strongly induced by high salinity, drought and osmotic stress, resulting in a remarkable increase of triacylglycerol （TAG） accumulation in T. mongolica plantlets. TmDGAT1a and TmDGAT1b activities were confirmed in the yeast H1246 quadruple mutant （DGA1, LRO1, ARE1, ARE2） by restoring DGAT activity of the mutant host to produce TAG. Overexpression of TmDGAT1a and TmDGAT1b in soybean hairy roots as well as in T. mongolica calli both resulted in an increase in oil content （ranging from 37% to 108%）, accompanied by altered fatty acid profiles.
文摘The enzymes of the acyl-coenzyme A:cholesterol acyltransferase(ACAT)family are responsible for the in vivo synthesis of neutral lipids.They are potential drug targets for the intervention of atherosclerosis,hyperlipidemia,obesity,type II diabetes and even Alzheimer’s disease.ACAT family enzymes are integral endoplasmic reticulum(ER)membrane proteins and can be divided into ACAT branch and acyl-coenzyme A:diacylglycerol acyltransferase 1(DGAT1)branch according to their substrate specificity.The ACAT branch catalyzes synthesis of cholesteryl esters using long-chain fatty acyl-coenzyme A and cholesterol as substrates,while the DGAT1 branch catalyzes synthesis of triacylglycerols using fatty acylcoenzyme A and diacylglycerol as substrates.In this review,we mainly focus on the recent progress in the structural research of ACAT family enzymes,including their disulfide linkage,membrane topology,subunit interaction and catalysis mechanism.
