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.
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
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