Fatty acid binding protein. Role in esterification of absorbed long chain fatty acid in rat intestine.
Fatty acid binding protein. Role in esterification of absorbed long chain fatty acid in rat intestine.
复制标题
脂肪酸结合蛋白。
DOI：
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发表时间：
1976
影响因子：
15.9
通讯作者：
J. Manning
中科院分区：
文献类型：
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作者：
R. Ockner;J. Manning
脂肪酸结合蛋白（FABP）是在肠粘膜和其他组织的细胞质中发现的12,000 mol wt的蛋白质，其对长链脂肪酸具有高亲和力。有人提出，FABP（可能包含一组密切相关的 12,000 mol wt 蛋白质）参与细胞脂肪酸转运和代谢。尽管早期的研究结果与这一概念一致，但目前的研究旨在更直接地检查其生理功能。将外翻的空肠囊在混合脂肪酸-单甘油酯-胆汁酸胶束中孵育，在存在或不存在等摩尔浓度的抑制油酸与FABP结合的两种化合物中的任一种的情况下：黄伐苷酸-N-甲基-葡萄糖酸酯和α-溴棕榈酸酯。油酸吸收、粘膜形态和[14C]乙酸盐的氧化仍然不受这些试剂的影响，但4分钟后油酸与甘油三酯的结合被抑制62-64%。黄伐苷酸的抑制作用随着油酸盐浓度的升高而可逆。在肠道微粒体中检查了这些化合物对甘油三酯生物合成酶的影响。黄伐吡酸和α-溴棕榈酸酯均不抑制酰基辅酶A：单甘油酯酰基转移酶。在部分纯化的 FABP 存在下，脂肪酸：辅酶 A 连接酶活性显着增强，这可能反映了对脂肪酸底物或酶-底物复合物形成的物理作用。在 0.1 mM 油酸存在下，该酶的活性仅被等摩尔的黄烷酸和 α-溴棕榈酸酯适度抑制，并且这种作用被 FABP 减弱或阻止。我们的结论是，在外翻的肠囊中，黄芪酸和 α-溴棕榈酸酯对甘油三酯合成的抑制不能解释为对脂肪酸摄取或内质网中酯化酶的影响，而是可以解释为反映了脂肪酸与 FABP 结合的抑制。这些发现进一步支持了 FABP 参与细胞脂肪酸转运和代谢的概念。 FABP 也有可能通过影响脂肪酸和酰基 CoA 的细胞内区室化，在细胞脂质代谢中发挥更广泛的作用。
Fatty acid binding protein (FABP) is a protein of 12,000 mol wt found in cytosol of intestinal mucosa and other tissues, which exhibits high affinity for long chain fatty acids. It has been suggested that FABP (which may comprise a group of closely related proteins of 12,000 mol wt) participates in cellular fatty acid transport and metabolism. Although earlier findings were consistent with this concept, the present studies were designed to examine its physiological function more directly. Everted jejunal sacs were incubated in mixed fatty acid-monoglyceride-bile acid micelles, in the presence or absence of equimolar concentrations of either of two compounds which inhibit oleate binding to FABP:flavaspidic acid-N-methyl-glucaminate and alpha-bromopalmitate. Oleate uptake, mucosal morphology, and oxidation of [14C]acetate remained unaffected by these agents, but oleate incorporation into triglyceride was inhibited by 62-64% after 4 min. The inhibition by flavaspidic acid was reversible with higher oleate concentrations. The effect of these compounds on enzymes of triglyceride biosynthesis was examined in intestinal microsomes. Neither flavaspidic acid nor alpha-bromopalmitate inhibited acyl CoA:monoglyceride acyl-transferase. Fatty acid:coenzyme A ligase activity was significantly enhanced in the presence of partially purified FABP, probably reflecting a physical effect on the fatty acid substrate or on the formation of the enzyme-substrate complex. Activity of the enzyme in the presence of 0.1 mM oleate was only modestly inhibited by equimolar flavaspidic acid and alpha-bromopalmitate, and this effect was blunted or prevented by FABP. We conclude that in everted gut sacs, inhibition of triglyceride synthesis by flavaspidic acid and alpha-bromopalmitate could not be explained as an effect on fatty acid uptake or on esterifying enzymes in the endoplasmic reticulum but rather can be interpreted as reflecting inhibition of fatty acid binding to FABP. These findings lend further support to the concept that FABP participates in cellular fatty acid transport and metabolism. It is also possible that FABP, by effecting an intracellular compartmentalization of fatty acids and acyl CoA, may play a broader role in cellular lipid metabolism.