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ABSTRACT
Dietary fats are essential for life and good health. Efficient absorption of dietary fats is dependent on the action of pancreatic triglyceride lipase. In the last few years, large advances have been made in describing the structure and lipolytic mechanism of human pancreatic triglyceride lipase and of colipase, another pancreatic protein that interacts with pancreatic triglyceride lipase and that is required for lipase activity in the duodenum. This review discusses the advances made in protein structure and in understanding the relationships of structure to function of pancreatic triglyceride lipase and colipase.
KEY WORDS: pancreas, protein structure, triglycerides
INTRODUCTION
Triglyceride lipases are ubiquitous enzymes required for all aspects of fat metabolism (5). Lipases mediate the digestion of dietary fats, the uptake of fats into various tissues, and the mobilization of fats inside cells. In humans, triglyceride lipases are found in the gastrointestinal tract, bound to epithelial surfaces, and inside fat storage cells. Although some lipases will degrade a broad range of ester compounds, they all hydrolyze the ester bonds in acylglycerols, including the triglycerides that comprise greater than 95% of the dietary fats in the western diet (48).
The degradation of dietary triglycerides is critical for their utilization because triglycerides are not absorbed by intestinal enterocytes. Dietary triglycerides must be cleaved into free fatty acids and monoacylglycerols before they are absorbed (27, 28). In the absence of lipases, dietary triglycerides are not absorbed and pass in the stools. The resulting steatorrhea produces fluid losses, weight loss or poor growth, and deficiencies of fat-soluble vitamins.
In humans, the digestion of dietary triglycerides begins in the stomach, where gastric lipase releases about IS% of the fatty acids (6). Lipases, secreted by pancreatic acinar cells, complete fat digestion in the proximal small intestine. Of the known pancreatic lipases, pancreatic triglyceride lipase (PTL), the archetype of the lipase family, is clearly essential for the efficient digestion of dietary triglycerides. In patients with congenital absence of PTL, 50-60% of dietary fats are not absorbed (19, 21). This pivotal role in fat digestion has made PTL the subject of numerous investigations into its properties over this century. Despite this interest in PTL, relatively little was understood about the molecular basis for lipolysis until recent years, when the...