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M Willson

Publications and source records attributed to M Willson.

22 records · Page 2Linked to original sources
PubMed1992

Substrate specificity of phospholipase B from guinea pig intestine. A glycerol ester lipase with broad specificity.

The substrate specificity of a calcium-independent, 97-kDa phospholipase B purified from guinea pig intestine was further investigated using various natural and synthetic lipids. The enzyme was equally active toward enantiomeric phosphatidylcholines under conditions allowing a strict phospholipase A activity. The lysophospholipase activity declined with the following substrates: 1-acyl-sn-glycero-3-phosphocholine greater than 1-palmitoyl-propanediol-3-phosphocholine greater than 1-palmitoyl-glycol-2-phosphocholine, suggesting some influence of the polar residue vicinal to the cleavage site. The enzyme also acted on various neutral lipids including triacylglycerol, diacylglycerol, and monoacylglycerol, whereas cholesteryl oleate remained refractory to enzymatic hydrolysis. The lipase hydrolyzed sequentially the sn-2 and sn-1 acyl ester bonds of diacylglycerol, although some direct cleavage of the external acyl ester bond could also occur, as shown with diacylglycerol analogues bearing a nonhydrolyzable alkyl ether or amide bond in the sn-1 or sn-2 position. The three main activities of the enzyme (phospholipase A2, lysophospholipase, and diacylglycerol lipase) were resistant to 4-bromophenacyl bromide, but they were inhibited by N-ethylmaleimide, 5,5'-dithiobis-(2-nitrobenzoic acid), and diisopropyl fluorophosphate, suggesting the possible involvement of both cysteine and serine residues in a single active site. It is concluded that guinea pig intestinal phospholipase B, which was also detected in rat and rabbit, is actually a glycerol ester lipase with broad substrate specificity and some unique enzymatic properties.

Animals↗
PubMed1991

Interactions between trypanocidal drugs and membrane phospholipids. A surface pressure, surface potential and electrophoretic mobility study.

Amphiphilic diphenyl methane derivatives exhibiting both antiproliferative and trypanocidal effects were studied with respect to their interactions with phospholipids, in monolayers and bilayers. These compounds, namely (4-benzyl)-phenoxy-2 trimethylammonium ethane iodide (D1), (4-tertiobutyl)-phenoxy-2 morpholinium ethane chloride (D2), and (4-benzyl)-phenoxy-2 morpholinium ethane chloride (D3), were shown to interact with phosphatidylcholine (PC) and phosphatidylserine (PS) in monolayers, as monitored by surface pressure and surface potential measurements. The film expansion of monolayers, on 10 mM NaCl subphase at pH 7.1, was more pronounced in the presence of D2 and D3 in the subphase before spreading of the lipids than with the injection of the drugs underneath a preformed film. Apparent binding constants of 10(4) M-1 were determined for both drugs from monolayer experiments. With D2 in the presence of PS, results of monolayer compressions and electrophoretic mobility measurements indicate binding of the drug to the lipid molecules only when the molecular area was large. D3 was shown to interact with PS, both in monolayers and bilayers, with a drug-to-lipid binding constant of about 2 x 10(4)M-1, as evaluated from electrophoretic mobility measurements on PS liposomes. These results, which indicate binding of these drugs to phospholipids in the order D2 less than D3, correlate with the biological activity of the drugs, and may account for the discrepancy observed between the drug concentrations required for biological and binding activities.

Animals↗