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Acyl coenzyme A dependent retinol esterification by acyl coenzyme A : diacylglycerol acyltransferase 1

機譯:?;o酶A依賴于?;o酶A的視黃醇酯化反應:二?;视王;D移酶1

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We provide biochemical evidence that enzymes involved in the synthesis of triacylglycerol, namely acyl coenzyme A:diacylglycerol acyltransferase (DGAT) and acyl coenzyme A:monoacylglycerol acyltransferase (MGAT), are capable of carrying out the acyl coenzyme A:retinol acyltransferase (ARAT) reaction. Among them, DGAT1 appears to have the highest specific activity. The apparent K values of recombinant DGAT1/ARAT for retinol and palmitoyl coenzyme A were determined to be 25.9 +/- 2.1 mu M and 13.9 +/- 0.3 mu M, respectively, both of which are similar to the values previously determined for ARAT in native tissues. A novel selective DGAT1 inhibitor, XP620, inhibits recombinant DGAT1/ARAT at the retinol recognition site. In the differentiated Caco-2 cell membranes, XP620 inhibits similar to 85% of the Caco-2/ARAT activity indicating that DGAT1/ARAT may be the major source of ARAT activity in these cells. Of the two most abundant ratty acyl retinyl esters present in the intact differentiated Caco-2 cells, XP620 selectively inhibits retinyl-oleate formation without influencing the retinyl-palmitate formation. Using this inhibitor, we estimate that similar to 64% of total retinyl ester formation Occurs via DGAT1/ARAT. These studies suggest that DGAT1/ARAT is the major enzyme involved in retinyl ester synthesis in Caco-2 cells. (c) 2005 Elsevier B.V. All rights reserved.
機譯:我們提供了生化證據,證明參與三?;视秃铣傻拿?,即?;o酶A:二?;视王;D移酶(DGAT)和?;o酶A:單?;视王;D移酶(MGAT),能夠進行?;o酶A:視黃醇?;D移酶(ARAT) 。其中,DGAT1似乎具有最高的比活。重組DGAT1 / ARAT對視黃醇和棕櫚酰輔酶A的表觀K值分別確定為25.9 +/- 2.1μM和13.9 +/- 0.3μM,這兩個值與先前在ARAT中確定的值相似。天然組織。一種新型的選擇性DGAT1抑制劑XP620在視黃醇識別位點抑制重組DGAT1 / ARAT。在分化的Caco-2細胞膜中,XP620抑制了約85%的Caco-2 / ARAT活性,表明DGAT1 / ARAT可能是這些細胞中ARAT活性的主要來源。在完整的分化的Caco-2細胞中存在的兩種最豐富的大鼠?;朁S基酯中,XP620選擇性地抑制視黃基油酸酯的形成,而不會影響視黃基-棕櫚酸酯的形成。使用這種抑制劑,我們估計通過DGAT1 / ARAT發生了約64%的總視黃酯形成。這些研究表明,DGAT1 / ARAT是參與Caco-2細胞視黃酯合成的主要酶。 (c)2005 Elsevier B.V.保留所有權利。

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