Lipases disease associations

Supplementation with pancreatic enzymes may reduce the pain and fatty diarrhea associated with chronic pancreatitis (Table 20-3). Best results are achieved in patients who have mild non-alcoholic pancreatic disease. Common pancreatic enzyme supplements contain lipase, amylase, and protease in varying proportions. Thus, the dose can be tailored to the patient s requirement for exogenous enzyme supplementation and response to therapy. 

Familial lipoprotein lipase deficiency is characterized by a massive accumulation of chylomicrons and a corresponding increase in plasma triglycerides or a type I lipoprotein pattern. Presenting manifestations include repeated attacks of pancreatitis and abdominal pain, eruptive cutaneous xanthomatosis, and hepatosplenomegaly beginning in childhood. Symptom severity is proportional to dietary fat intake, and consequently to the elevation of chylomicrons. Accelerated atherosclerosis is not associated with this disease. 

Tetrahydrolipstatin is a lipase inhibitor developed and marketed by Roche (Basel, Switzerland) as an anti-obesity drug. With the incidence of obesity rising rapidly in the industrialized nations, having reached 33% of all adults in the United States and more than a quarter of all French schoolchildren, this problem will rapidly cease to remain one of lifestyle and enter the arena of medical costs associated with the diseases stemming from obesity. 

Normally there is very little fat in the feces. However, fat content in stools may increase because of various fat malabsorption syndromes. Such increased fat excretion is steatorrhea. Decreased fat absorption may be the result of failure to emulsify food contents because of a deficiency in bile salts, as in liver disease or bile duct obstruction (stone or tumor). Pancreatic insufficiency may result in an inadequate pancreatic lipase supply. Finally, absorption itself may be faulty because of damage to intestinal mucosal cells through allergy or infection. An example of allergy-based malabsorption is celiac disease, which is usually associated with gluten intolerance. Gluten is a wheat protein. An example of intestinal infection is tropical sprue, which is often curable with tetracycline. Various vitamin deficiencies may accompany fat malabsorption syndromes. 

Type I lipoproteinemia is generally caused by the inability of the organism to clear chylomicrons. The problem may be defective ApoC-II or a defective lipoprotein lipase. Very often, chylomicron clearance may be affected by injection of heparin, which apparently releases hepatic lipase from the liver into the circulation. ApoE disorders may be associated with type III lipoproteinemia, in which clearance of IDL is impeded. Increases in circulatory LDL are usually caused by a decrease in tissue receptors specific for ApoB-100. An extreme case of type Ha hyperlipoproteinemia is familial hypercholesterolemia, in which serum cholesterol levels may be as high as 1000 mg/dL and the subjects may die in adolescence from cardiovascular disease. There is total absence of ApoB-100 receptors. Mild type Ila and lib lipoproteinemias are the most commonly occurring primary lipoproteinemias in the general population. 

Figure 26-18 Exogenous lipoprotein metabolism pathway. TG, Triglyceride CE, cholesterol ester FC, free cholesterol Ft, phospholipids HDL, hIgh-density lipoproteins FA, fatty acid LPL, lipoprotein lipase 6, apolipoprotein B-48 A, apolipoprotein A-i C, apolipoprotein C-ll , apolipoprotein E. (From Rifai N. Lipoproteins and apolipoproteins Composition, metabolism, and association with coronary heart disease. Arch Pathol Lab Med 1986 10 694-701. Copyright 1986, American Medical Association.)...

FAs liberated from food during absorption are metabolized more easily if they are short or medium chain, i.e., C10 or below. The sn-2 monoacylglycerols can be absorbed directly. Therefore, essential or desired FAs are most efficiently utilized from the sn-2 position in acylglycerols. In accordance with this, TAGs with short-chain FAs (SCFAs) or MCFAs at the sn-1 and sn-3 positions and PEFAs at the sn-2 position are rapidly hydrolyzed with pancreatic lipase (sn-1,3-specific lipase) and absorbed efficiently into mucosal cells. SCFAs or MCFAs are used as a source of rapid energy for infants and patients with fat malabsorption-related diseases. LCFAs, especially DHA and arachidonic acid, are important in both the growth and development of an infant, while n-3 PEFAs have been associated with reduced risk of cardiovascular disease in adults (Christensen et al., 1995 Jensen et al., 1995). 

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