Lipases: Function & Diseases

Lipases form a group of water-soluble enzymes that contribute to the breakdown of fats in catabolic metabolism. The main group of lipases, pancreatic and phospholipases, catabolize lipids such as tri- and diglycerides and cholesterol esters by catalytically cleaving simple fatty acids and glycerol. The substances are further metabolized by the body or further used for anabolic purposes as basic substances.

What are lipases?

Originally, only the fat-splitting enzymes produced in the pancreas were included in the group of lipases. However, in a broader sense, lipases formed in salivary glands of the tongue and in the stomach, as well as phospholipases and lipoprotein lipases, also belong to enzyme group III (hydrolases) according to the international classification. The common feature of all lipases is that they do not require coenzymes for their bioactivity. In general, lipases are secreted by exocrine glands such as pancreas, salivary glands of the tongue, and in smaller amounts by the mucosa of the stomach. This means that lipases are bioactive extracellularly in the oral cavity, stomach and small intestine. However, there are also lipases that work intracellularly. To prevent the cell from being attacked by the intracellular lipase, it is present in cell organelles enclosed by special membranes called lysosomes. Lysosomes are roughly comparable to vesicles, which enclose substances that need to be transported to specific locations in the cell but are not soluble in the aqueous cytosol.

Function, action, and roles

The two main tasks and functions of lipases are, on the one hand, to break down fats contained in food so that they can be absorbed by the intestinal mucosa of the small intestine and, on the other hand, to catabolize endogenous fat reserves when necessary so that the energy released in the process is available to the body. The preparation for the catabolism of dietary fats begins in the mouth by the tongue lipases and continues in the stomach under the action of the gastric lipase secreted by certain cells of the gastric mucosa. The main work of preparing the fats for absorption by the enterocytes of the intestinal mucosa is performed by the pancreatic and phospholipases, the phospholipases also being produced by exocrine pancreatic cells and directed into the small intestine. While pancreatic lipase mainly cleaves fatty acids and breaks down triglycerides into monoglycerides, phospholipase primarily supports and catalyzes the hydrolysis of phospholipids. Lipoprotein lipases play an important role in the metabolism of endogenous fats. They break down lipoproteins such as LDL, which is under general suspicion, and ensure the incorporation of the released fatty acids into the adipose tissue. Although a high activity of lipoprotein lipases can lower the LDL content of cholesterol, this occurs at the price of further increase in adipose tissue. Hormone-sensitive lipase (HSL) plays a special role. It also intervenes in the body’s internal lipid metabolism and, by breaking down the body’s own fats, creates basic substances from which all steroid hormones are synthesized, such as the glucocorticoid cortisol, the sex-specific androgens and estrogens, the mineral corticoid aldosterone, and many others.

Formation, occurrence, properties, and optimal levels

Lipases are synthesized mostly by exocrine gland cells in the salivary glands below the tongue, in gastric cells of the gastric mucosa, and in specialized cells of the pancreas. Lipases may also reside within cells as lysosomal lipases in cell inclusions called lysosomes. Therefore, the greatest accumulation of lipases is found in the digestive tract, especially in the duodenum. Pancreatic lipase is also found in blood serum and can be detected by laboratory methods. Reference values for healthy women and men range from about 13 to 60 units per liter (U/l). It should be noted that reference values are subject to wide variations depending on the laboratory method used and the time of day and year. Elevated values may indicate pancreatitis, an inflammation of the pancreas, or impaired renal function if the abnormalities cannot be otherwise explained. The catalytic effect of lipases is based on their tertiary structure in conjunction with certain amino acid sequences.In most cases, so-called triads are present, sequences of three that are normally composed of the amino acids serine, histidine and aspartic acid. When food is cooked, the tertiary structures of most lipases are destroyed, so that they lose their catalytic effect.

Diseases and disorders

Lipases are supplied to the body by self-synthesis in exocrine cells of various organs such as the pancreas, stomach, and salivary glands and by feeding foods that may contain functional lipases. If the above reference values of 13 to 60 U/l are significantly under- or exceeded and cannot be explained otherwise, this may indicate the presence of a disorder in lipid metabolism or point to inflammation of the pancreas (pancreatitis). An increase in pancreatic lipase in the blood serum can also be caused by mechanical obstruction of the bile duct into the intestine by gallstones. The backlog of enzymes in the pancreas is then mitigated by increased transfer to the blood serum. Elevated lipase levels can be caused by intestinal obstruction, impaired kidney function, gallbladder inflammation, diabetes, hepatitis, and other conditions in addition to pancreatitis. A deficiency of self-produced lipases is symptomatically expressed by so-called fatty stools or by fatty diarrhea, called steatorhhoea. The deficiency of lipases can be caused by pathological disorders of the pancreas, by a pancreatic tumor or, for example, by cystic fibrosis. Chronic deficiency of lipases risks promoting the development of atherosclerotic changes.