Is a role of phospholipase A(2) in cholesterol gallstone formation phospholipid species-dependent?
Phospholipase A(2) plays a role in cholesterol gallstone formation by hydrolyzing bile phospholipids into lysolecithin and free fatty acids. This study investigated its effects on cholesterol crystallization in model bile systems. Supersaturated model bile solutions with different cholesterol saturation indexes (1.2, 1.4, and 1.6) were prepared using cholesterol, taurocholate, and egg yolk phosphatidylcholine, soybean phosphatidylcholine, palmitoyl-oleoyl phosphatidylcholine, or palmitoyl-linoleoyl phosphatidylcholine. Then the effect of digestion of phosphatidylcholine by phospholipase A(2) on bile metastability was assessed by spectrophotometry and video-enhanced differential contrast microscopy. Addition of phospholipase A(2) caused the release of free fatty acids in a time-dependent manner. Cholesterol crystallization was enhanced by an increased crystal growth rate in model bile containing hydrophilic species such as soybean or palmitoyl-linoleoyl phosphatidylcholine, consisting predominantly of polyunsaturated fatty acids. Because phospholipase A(2) enhanced cholesterol crystallization in bile containing hydrophilic phosphatidylcholine species, but not hydrophobic phosphatidylcholine species, release of polyunsaturated fatty acids by hydrolysis may be responsible for such enhancement. Therefore, the role of phospholipase A(2) in cholesterol gallstone formation depends on the phospholipid species present in bile, so that phospholipid species selection during hepatic excretion is, in part, crucial to the cholesterol stone formation.
Sunami
Y
Y
First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan.
Tazuma
S
S
Chayama
K
K
D001646:Bile / Q000737:chemistry; D002769:Cholelithiasis / Q000209:etiology*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D003460:Crystallization; D005230:Fatty Acids, Nonesterified / Q000096:biosynthesis; D006868:Hydrolysis; D008244:Lysophosphatidylcholines / Q000096:biosynthesis; D010741:Phospholipases A / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D013379:Substrate Specificity
D005230:Fatty Acids, Nonesterified; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D002784:Cholesterol; D010741:Phospholipases A