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PANCREATIC LIPASE
DONE BY:
BARAKATHU PEER FATHIMA
INDIA
Pancreatic Lipase
 Pancreatic lipase, also known as pancreatic
triacylglycerol lipase, is secreted from
the pancreas, and is the
primary lipase (enzyme)
that hydrolyzes (breaks down)
dietary fat molecules in the human digestive
system, converting triglyceride substrates
found in ingested oils
to monoglycerides and free fatty acids by
breaking hydrogen bonds.
Pancreatic Lipase
 Lipase requires a high pH for its
activation among food enzymes. That is
why fats are the hardest of all foods to
digest.
 Triacylglycerol + 2 H2O 2-monoacylglycerol + 2 fatty acid anions
Mechanism
 Bile salts secreted from the liver and
stored in gallbladder are released into
the duodenum where they coat and
emulsify large fat droplets into smaller
droplets, thus increasing the
overall surface area of the fat, which
allows the lipase to break apart the fat
more effectively
Mechanism
 The resulting monomers (2 free
fatty acids and one 2-
monoacylglycerol) are then moved
by way of peristalsis along the small
intestine to be absorbed into
the lymphatic system by a
specialized vessel called a lacteal.
Mechanism
The resulting fatty acids and
monoacylglycerols
are incorporated into bile salt-
phospholipid micelles. These
micelles are absorbed into the
brush border of the small intestine
and eventually enter the
bloodstream as chylomicrons.
Pancreatic Lipase
 Cleaves acylglycerols mainly to FA and
2-monoacylglycerols
 Requires solubilization of the substrate
 Also requires colipase (secreted by the
pancreas) that anchors and activates the
enzyme
 Absorption of resulting FA and monoAG
requires bile salts micelles
Hydrolysis of cholesterol esters
 By pancreatic cholesterol esterase
 The free cholesterol is transported in
the bile acid micelles and absorbed
through the brush border
 Here, it is reacylated with acyl-CoA
Hydrolysis of triglycerides
Reaction
Pancreatic Lipase
 Unlike some pancreatic enzymes that are
activated by proteolytic
cleavage (e.g. trypsinogen), pancreatic lipase
is secreted in its final form. However it only
becomes efficient in the presence
of colipase in the duodenum in the presence
of bile acids provided by the liver.
 In humans, pancreatic lipase is encoded by
the PNLIP gene.
Structure of Pancreatic Lipase
Cartoon diagram of
Human Pancreatic Lipase
secondarystructure:
alpha helices in red,
beta sheets in yellow, and
random coil in green in
complex with pigcolipase
(colored blue) and
a small molecule inhibitor
(upper left).
Structure
A computer-
generated image of
a type of pancreatic
lipase (PLRP2) from
the guinea pig.
Biochemical properties
 Pancreatic lipase is a water-soluble lipolytic
enzyme that hydrolyse ester linkages of
triglycerides
 The enzyme is a single-chain glycoprotein of
449 amino acids. Structural results suggest
that Ser 152 is the nucleophilic residue
essential for catalysis
 forms part of an Asp-His-Ser triad that is
chemically analogous to, but structurally
different from, that of the serine proteases
Inhibition of pancreatic lipase
activity
 Natural products that inhibit the activity
of pancreatic lipase may suppress
dietary fat absorption from the small
intestine. Potential candidates include
basic peptides and proteins, which
destroy the lipid emulsion by binding to
bile salts, thus suppressing the activity
of pancreatic lipase.
Inhibition
 Recently, protamine, purothionin
and histone, which belong to a class of
basic proteins, were reported to inhibit
lipase . These substances inhibit lipase
in substrates containing
phosphatidylcholine. From these
results, it was suggested that these
compounds inhibit lipase activity by
interaction with triolein-
phosphatidylcholine
Pancreatic Lipase
People who are concerned with
losing weight may be more than
familiar with this enzyme and what
it does. That’s because several
dieting products have surfaced that
boast the ability to block its activity
in order to inhibit the absorption of
fats.
Pancreatic Lipase
In fact, orlistat is a prescription
medication that prevents up to 30%
of dietary fats, including
triglycerides, from being absorbed
through the intestines. This results
in a reduction in total calorie intake
and, subsequently, weight loss.
Research on Lipases
Researchers have learned about a few
other unique properties of pancreatic
lipase by studying hibernating
squirrels. While this enzyme is
normally found in the intestines, it is
found in great concentration in the
hearts of these animals, but only from
late fall until early spring.
Research on Lipase
 Apparently, after completing the job of
digesting dietary fats for storage during the
big sleep, the enzyme takes up residence in
the heart to help it function while body
temperature and oxygen levels
dramatically decline. What
is particularly interesting about this is that
most other enzymes are rendered inactive
below certain temperatures, while this one
retains about 30% of its activity.
Hyper production
 Excessive production of this enzyme may
indicate the presence of certain disorders,
most notably:
 inflammation of the pancreas, or pancreatitis.
 bowel obstruction,
 peptic ulcers, or
 kidney disease, and
 are also a temporary side effect of some
medications, like morphine and codeine.
Hypo production- Deficiency
 Diminished levels may suggest that
 Some cells of the pancreas are
irreversibly damaged.
 Pancreatic lipase monitoring is also
used to help diagnose
 Crohn's disease,
 Cystic fibrosis, and
 Celiac disease.
Deficiency
 Lipase deficient people can be expected
to have a tendency towards high
cholesterol, high triglycerides,
 Difficulty losing weight and
 Diabetes, or
 A tendency towards glucosuria (sugar in
the urine without symptoms of
diabetes), which can lead to
 Heart disease.
Lipase deficiency
Because lipase requires the co-
enzyme chloride, lipase deficient
people have a tendency towards
hyphochlorhydria (low chlorides in
our electrolyte balance).
Lipase deficiency
 Lipase deficient people have decreased cell
permeability, meaning nutrients cannot get in
and the waste cannot get out of the cell. For
example, diabetics are lipase deficient and
cannot get glucose into their cells, and wastes
or unwanted substances cannot get out.
People with "hidden viruses" that are often
diagnosed with "Chronic Fatigue Syndrome"
also fall into this category. Lipase modulates
cell permeability so that nutrients can enter
and wastes can exit.
Lipase deficiency
 A common symptom of lipase deficiency
is muscle spasms. This is not the
"muscle cramp" (tetany) resulting from
low ionized blood calcium. It commonly
occurs as trigger point pain in the
muscles across the upper shoulders, but
it can occur in other muscles, such as
those in the neck or anywhere in the
small or large intestines including the
muscles of the rectal tissues.
Lipase deficiency
People with "spastic colon" may be
lipase deficient. They are given toxic
muscle relaxant drugs to control the
symptoms
Lipase deficiency
The condition of vertigo, or
labrynthis, also called
Meniere's Disease (dizziness
aggravated by movement such as
walking or driving), can result from
lipase deficiency.
Lipase deficiency
 A nutritionist saw this condition develop
suddenly in a young man after the typical
American fat challenge test--a meal which
consisted of a fried fish sandwich with tartar
sauce, double cheeseburger plus a bag of
french fries. The dizziness was accompanied
by severe nausea and vomiting which was
aggravated by movement. This condition
lasted several days. Lipase can relieve a
condition like this, often within minutes.
Lipase deficiency
The condition of menopause is
often associated with lipase
deficiency because lipase addresses
the gonadal tissue.
Thank you