Bile salt dependent lipase

Sbarra, V., Bruneau, N., Mas, E., Hamosh, M., Lombardo, D., Hamosh, P. 1998. Molecular cloning of the bile salt-dependent lipase of ferret lactating mammary gland An overview of functional residues. Biochim. Biophy. Acta 1393, 80-89. 

Lipolysis starts at the water/emulsion interphase. The major enzymes involved are pancreatic lipase, pancreatic phospholipase A2, and pancreatic cholesterol esterase, the latter also named bile-salt-dependent lipase. 

The bile-salt-dependent lipase of pancreatic juice has many names such as cholesterol esterase, nonspecific lipase, the most rational being carboxyl ester lipase [27], In the case of water-insoluble substrates this enzyme has an absolute requirement for bile salts specifically having hydroxyl groups in the 3a and la positions [28.29]. The best documented role for this enzyme is to allow the absorption of dietary cholesterol, through hydrolysis of cholesterol esters in the lumen. The enzyme also catalyzes the esterification of cholesterol and a role for it has been proposed in cholesterol absorption [30]. In addition, a wide range of primary and secondary fatty acyl esters including glycerides, vitamin A and E esters are hydrolyzed by this enzyme. 

Bile salt dependent lipase, also known as carboxyl ester lipase, secreted by acinar cells of the pancreas and associated with LDL in blood, locates with SMC in atherosclerotic lesions and triggers SMC proliferation (434). It may also play a role in lipoprotein metabolism and oxLDL-induced atherosclerosis (reviewed in ref. 435). 

Auge N, Rebai O, Lepetit-Thevenin J, et al. Pancreatic bile salt-dependent lipase induces smooth muscle cells proliferation. Circulation 2003 108 86-91. 

Aubert-Jousset E, Garmy N, Sbarra V, Fantini J, Sadoulet MO, Lombardo D. The combinatorial extension method reveals a sphingolipid binding domain on pancreatic bile salt-dependent lipase role in secretion. Structure. 2004 12(8) 1437-1447. 

Bernback, S., Blackberg, L., Hernell, O. 1989. The complete digestion of human milk triacyl-glycerol in vitro requires gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase.. / Clin. Invest. 85, 1221-1226. 

The various esters of cholesterol, retinoyl esters, esters of vitamin D and E, probably depend solely on the activity of carboxylester lipase for their hydrolysis. They are, before their uptake by the enterocytes, transformed into the corresponding alcohols to form mixed micelles with bile salts. Carboxylester lipase catalyzes not only the cleavage of esters but also their formation. The most studied example is the reversible esterification of cholesterol, which is favored by low bile salt concentrations and pH [42]. Additionally, the laige specificity of carboxylester lipase probably functions as a first-line detoxification mechanism for a broad variety of orally ingested xenobiotics. 

Pancreatic carboxytester lipase, secreted by the pancreas as an active enzyme without proteolytic activation, displays broad substrate specificity and has therefore received many names in the literature carboxylesteraae, bile salt-stimulated (or activated or dependent) lipaae (due to its absolute requirement for bile salts to hydrolyze insoluble substrates), carbaxylester lipase or hydrolase, cholesterol... 

C) The ability of bile salts to bind lipase is concentration dependant. 

Values of pH ranging between 8.2 and 9.2 have been described as optimum for pancreatic lipase (197, 202, 210), the optimum depending on the species used for preparation of the enzyme [Borgstrom (225)]. The optimum pH may also depend on the presence or absence of bile salts (269). 

Willstatter ef al. 196, 301) found that activation could be observed in an alkaline medium but not in an acid medium. Inhibition of tributyrin hydrolysis by bile salts at pH values below 7.0 was also observed by Click and King (297), and Wills (302) found that, although triolein hydrolysis by lipase was stimulated by sodium taurocholate in an alkaline medium, it was inhibited at pH values below 7.0. The effect of the bile salt may also depend on the length of fatty acid chain of the triglyceride under investigation. Thus Click and King (297) showed that, at pH 7.0, sodium taurocholate inhibited tributyrin hydrolysis but stimulated triolein hydrolysis. Similar results were obtained by Wills (302), who found that triacetin hydrolysis was inhibited and triolein hydrolysis stimulated by equivalent concentrations of sodium taurocholate. 

It has recently been established (214, 294) that bile salt may affect the temperature dependence of lipase. In a heterogeneous system the rate of lipase hydrolysis is not affected by temperature, but the hydrolysis becomes markedly temperature dependent when bile salts are added (Fig. 6). 

Phylloquinone is highly lipophilic however, at low concentrations it is transported by a saturable, energy-dependent transport system across the gut wall, mainly in the upper small intestine. Phylloquinone in foods consisting of plant tissues is much less readily bioavailable for absorption than the pure vitamin since it is tightly bound to the thylakoid membranes of the chloroplasts, and the absorption of vitamin K from plant foods is considerably improved by including additional fat in the meal. Its absorption also depends on the stimulation of bile salt and pancreatic lipase secretions. The long-chain menaquinones, which are even more lipophilic, are only passively absorbed and are much less bioavailable for absorption than phylloquinone. However, if given by injection (e.g., intracardially), they can be even more functionally active than phylloquinone. 

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