Coleman R A, Rao P, Fogelsong R J, Bardes E S
Department of Pediatrics, Duke University Medical Center, Durham, NC.
Biochim Biophys Acta. 1992 Apr 23;1125(2):203-9. doi: 10.1016/0005-2760(92)90046-x.
2-Bromopalmitate and 2-bromopalmitoyl-CoA have been shown to inhibit a variety of enzymes and proteins associated with lipid metabolism. We found that both of the brominated compounds were non-competitive inhibitors of two microsomal activities of triacylglycerol biosynthesis, the mono- and diacylglycerol acyltransferases. With both compounds, the calculated Ki values were lower than the Km value for the palmitoyl-CoA substrate. In addition to inhibiting two other lipid synthetic activities, fatty acid CoA ligase and glycerol-3-P acyltransferase, 2-bromopalmitate and 2-bromopalmitoyl-CoA also inhibited two microsomal enzyme activities that are not related to lipid metabolism, NADPH cytochrome-c reductase and glucose-6-phosphatase. Inhibition of the three acyltransferases and fatty acid CoA ligase could be overcome by the addition of phospholipid vesicles, and 2-bromo[14C]palmitate readily labeled a large number of membrane-bound proteins as well as cytosolic proteins that had been solubilized in SDS. Thus, it appears likely that the inhibitory properties of the brominated compounds strongly depend on the effective concentration of the inhibitor within membranes rather than on any specific affinity for an acyl-chain binding region of the enzyme.
2-溴软脂酸酯和2-溴软脂酰辅酶A已被证明可抑制多种与脂质代谢相关的酶和蛋白质。我们发现这两种溴化化合物都是三酰甘油生物合成的两种微粒体活性（单酰甘油和二酰甘油酰基转移酶）的非竞争性抑制剂。对于这两种化合物，计算得出的Ki值均低于棕榈酰辅酶A底物的Km值。除了抑制另外两种脂质合成活性（脂肪酸辅酶A连接酶和甘油-3-磷酸酰基转移酶）外，2-溴软脂酸酯和2-溴软脂酰辅酶A还抑制了两种与脂质代谢无关的微粒体酶活性，即NADPH细胞色素c还原酶和葡萄糖-6-磷酸酶。添加磷脂囊泡可以克服对三种酰基转移酶和脂肪酸辅酶A连接酶的抑制作用，并且2-溴[14C]软脂酸酯很容易标记大量膜结合蛋白以及已在SDS中溶解的胞质蛋白。因此，溴化化合物的抑制特性似乎很大程度上取决于抑制剂在膜内的有效浓度，而不是对酶的酰基链结合区域的任何特异性亲和力。
