Fält Helen, Hernell Olle, Bläckberg Lars
Department of Medical Biosciences, Physiological Chemistry, Umeå University, Umeå, Sweden.
Pediatr Res. 2002 Oct;52(4):509-15. doi: 10.1203/00006450-200210000-00009.
Bile salt-stimulated lipase (BSSL), or carboxyl ester lipase, is a constituent of exocrine pancreatic secretion and, in some species, including humans, also of milk. BSSL has been suggested to have a direct effect on intestinal uptake of dietary cholesterol besides being the key enzyme in the hydrolysis of fat-soluble vitamins and cholesterol esters. Furthermore, an intestinal heparin-containing receptor for the enzyme has been implicated. If BSSL promotes dietary cholesterol utilization, this might be of particular importance in the neonatal period, which is characterized by a high need of cholesterol for membrane synthesis. We have studied binding of BSSL to intestinal membranes in vitro and if such binding affects the uptake of cholesterol. BSSL bound avidly to rat intestinal microvesicle membranes and the binding was inhibited by addition of free heparin or heparin fragments. In this model system, we could not demonstrate any effect of BSSL on cellular uptake of free cholesterol. However, if esterified rather than free cholesterol was present in the incubation, hydrolysis by BSSL was the rate-limiting step in cellular cholesterol uptake. We therefore conclude that BSSL is important for utilization of dietary cholesterol only by hydrolyzing cholesterol esters and not by acting as a transport protein.
胆汁盐刺激脂肪酶（BSSL），即羧基酯酶，是胰腺外分泌液的一个组成部分，在包括人类在内的一些物种中，也是乳汁的组成部分。除了是脂溶性维生素和胆固醇酯水解的关键酶外，BSSL还被认为对膳食胆固醇的肠道吸收有直接作用。此外，还涉及该酶的一种含肝素的肠道受体。如果BSSL能促进膳食胆固醇的利用，这在新生儿期可能尤为重要，因为新生儿期的特点是膜合成对胆固醇的需求量很大。我们研究了BSSL在体外与肠膜的结合情况，以及这种结合是否会影响胆固醇的吸收。BSSL与大鼠肠微泡膜紧密结合，加入游离肝素或肝素片段可抑制这种结合。在这个模型系统中，我们未能证明BSSL对游离胆固醇细胞摄取有任何影响。然而，如果孵育液中存在酯化胆固醇而非游离胆固醇，BSSL的水解是细胞摄取胆固醇的限速步骤。因此，我们得出结论，BSSL仅通过水解胆固醇酯而不是作为转运蛋白对膳食胆固醇的利用起重要作用。
