How Lipases Helps Break Down Fats
Fats, such as the fats in milk, need to be digested by your body. They are broken down into fatty acids and glycerol by an enzyme called lipase. Gastric lipase, secreted by the stomach lining, has a pH value for optimal activity around neutrality and would appear, therefore, to be essentially inactive in the strongly acid environment of the stomach. It is suggested that this enzyme is more important for infant digestion since the gastric pH in infancy is much less acid than later in life. Most lipid digestion in the adult occurs in the upper loop of the small intestine and is accomplished by a lipase secreted by the pancreas.
In recent years our knowledge of lipases has increased dramatically, especially in the areas of molecular structure and mechanism of action. The term lipase usually refers to triacylglyceride lipases, rather than the related phospholipases.
Lipases are enzymes which catalyse the hydrolysis of triglyceride to give di- and mono- glycerides, glycerol and free fatty acids. Enzymes such as proteases and carbohydrases have been used industrially for a number of years and corner the largest share of the world wide enzyme market. Whilst lipases at present account for less than 5% of the market, this share has the potential to increase dramatically via a wide range of different applications. Possible medical applications of lipase are under consideration, for example inhibition of the human enzyme as a method of reducing fatty-acid adsorption is being investigated as a possible treatment for obesity.
Lipase breaks down neutral fats (triglycerides) into glycerol (an alcohol) and fatty acids. Before lipase can digest fat, bile, an emulsifier, must break the fat down into smaller units. People who are low in HCl cannot make adequate bile. HCl deficiency is caused by protease deficiency (required to provide adequate acidity) and lipase deficiency (required to carry chlorides). Thus lipase deficiency, inadequate HCl, and stagnation of bile are interrelated.
There are two types of lipase-deficient people. The first are those who are truly fat intolerant, get sick when they eat fat, and have gallbladder problems. These people substitute sugar for fat. The second are people who are complex-carbohydrate intolerant and make up for it by eating excessive amounts of fat. These people gradually develop a lipase deficiency.
Lipase is important in maintaining optimum cell permeability, which allows nutrients to flow easily into the cells and wastes to flow out. Two conditions arising from lipase deficiency are diabetes and glucosuria (sugar in the urine without symptoms of diabetes). Most people associate diabetes with sugar intolerance, but fat intolerance is the major enzyme culprit. The inability to digest fat interferes with insulin metabolism and the transport of glucose into the cell by insulin.
Lipase-deficient people may also have one or more of the following conditions or a tendency towards them: high cholesterol and/or high blood triglycerides, high bloodpressure, difficulty losing weight, and varicose veins. They may also be deficient in many fat-soluble nutrients, including vitamins A, D, and E.
Obesity is a condition affecting one-third off the U.S. population and is a major risk actor for the development of Type 2 diabetes, hyperlipidemia (increased levels of fat in the blood), hypertension (high blood pressure), and other disorders of the heart and lungs. Individuals with the onset of obesity during childhood or adolescence are at an increased risk of obesity-related, diseases, both during adolescence and later in adult life.
African American girls and women are at an increased risk for obesity, and have substantial rates of obesity-related diseases and causes of death. Further, many African American adult women fail to respond to many of the therapeutic approaches used to treat obesity. At present there are no medical therapies proven effective for the correction of severe obesity in children or adolescents.
One medication that may have a favorable risk-benefit ratio in pediatric populations is Orlistat (Xenical, Hoffmann LaRoche). Orlistat works by preventing the action of enzymes in the digestive process, interfering with the absorption of approximately 1/3 of the fat eaten in the diet. Xenical appears to be effective for reducing weight and obesity-associated diseases in obese adults.
Orlistat is used as an aid to help you lose weight. The medicine prevents the digestion of some of the fat you eat. Fats that are not digested cannot be absorbed and therefore do not contribute calories. To give the greatest weight loss, orlistat must be used with a weight-reduction diet.
Orlistat prevents the absorption of some of the fat you eat. Therefore, you should take it during the meal or within 1 hour of eating. If you occasionally miss a meal or eat a meal that contains no fat, you should skip the dose of orlistat.
Because orlistat may decrease the amount of some vitamins that your body can absorb from food, you will need to take a multivitamin supplement once a day. Take the vitamin supplement at least 2 hours before or after taking orlistat.
An article in the Physician's Weekly reported that an investigational weight-control drug has given obese diabetics a metabolic bonus.
Pounds shed with the help of orlistat led to better glucose control and lower doses of hypoglycemic agents in a multicenter randomized trial. The intestinal lipase inhibitor, endorsed by an FDA advisory panel, reduces weight by decreasing the absorption of dietary fat.
In the 52-week study, which began with five weeks of a hypocaloric diet alone, 163 patients taking 120 mg of orlistat three times a day lost a mean 6.2% of their initial body weight, vs 4.3% for 159 placebo controls, said Dr. Priscilla Hollander of Baylor. Similar results were seen among 892 nondiabetic patients followed for two years in another multicenter trial, reported Dr. Charles Lucas of William Beaumont Hospital in Royal Oak, Mich.
After a year with all patients on a hypocaloric diet while half took orlistat and half placebo, the drug group had a mean loss of 8.8% of initial body weight, vs 5.8% for controls.With a eucaloric diet in the second year, orlistat-treated patients regained only 35% of lost weight, vs 63% for controls. Lipid and glucose profiles were also better.
Orlistat groups had mild to moderate GI side effects.
Familial lipoprotein lipase deficiency (hyperlipoproteinemia) is characterized by absence of lipoprotein lipase (LPL) activity, which results in chylomicronemia and plasma triglyceride concentrations usually greater than 2000 mg/dl in the untreated state. Familial lipoprotein lipase deficiency usually presents in childhood with episodes of abdominal pain, recurrent acute pancreatitis, eruptive cutaneous xanthomata, and hepatosplenomegaly. The pancreatitis can be associated with total pancreatic necrosis and death. The disease affects both sexes equally. About 25% of patients develop symptoms before the age of one year and the majority develop symptoms before the age of ten years; however, some patients present for the first time during pregnancy. The severity of symptoms correlates with the degree of chylomicronemia, which varies by dietary fat intake.
The abdominal pain is usually mid-epigastric with radiation to the back. It may be diffuse and mimic an acute abdomen, often leading to unnecessary abdominal exploratory surgery. The pain can vary from mildly bothersome to incapacitating. The pain may result from chylomicronemia or from pancreatitis. The secondary complications of lipoprotein lipase deficiency Em Dash diabetes mellitus, steatorrhea, and pancreatic calcification Em Dash usually do not occur before middle age.
Neuropsychiatric findings, including mild dementia, depression, and memory loss, have also been reported with chylomicronemia.
- Sophie Clarke. York Structural Biology Laboratory. The University of York
- Safety and Efficacy of Orlistat (Xenical, Hoffmann LaRoche) in African American and Caucasian Children and Adolescents with Obesity-Related Comorbid Conditions. Warren Grant Magnuson Clinical Center. 98-CH-0111
- Judy Ismach. Lipase Inhibitor Aids Weighty Diabetics and Nondiabetics. Physician's Weekly Vol. XIV, No. 33
- John D Brunzell, MD. Familial Lipoprotein Lipase Deficiency
- Chait A, Robertson HT, Brunzell JD (1981) Chylomicronemia syndrome in diabetes mellitus. Diabetes Care 4:343-8