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Biochem 32 Digestion and Transport of Dietary Lipids

Terms in this set (50)

where are the two places amylase is produced?
salivary glands
pancreatic acinar cells
How do you measure lipase
1. incubating the serum sample with a known amount of TAG. The serum lipase will generate two free fatty acids and one 2-monacylglycerol for each
triglyceride. Monoacylglycerol lipase is then added (to convert the 2- monoacylglycerol to free glycerol), as is glycerol kinase (to convert glycerol to glycerol 3-phosphate) and glycerol 3-phosphate oxidase
(which converts molecular oxygen and glycerol 3-phosphate to dihydroxyacetone phosphate and hydrogen peroxide). The H2O2ngenerated can be determined colorimetrically using an appropriate
chromogen and horseradish peroxidase.

2. Turbidimetric (based on light scattering) - As the lipase hydrolyzes the fatty acids from the TAG, the turbidity decreases, and this can be measured and compared to a standard curve generated with known lipase amounts.
what do lingual and gastric lipases do?
preferentially hydrolyze short and medium chain fatty acids (under 12 carbons)

* most active in infants and young children
who drink relatively large quantities of cow's milk, which contains TAGs with a high percentage of short- and MCFA
What is the current %fat recommendation of the total diet?
no more than 30% of total calories (compared to 38% in the typical American diet)
The bile salts are ___________________ (containing both
hydrophobic and hydrophilic components), synthesized in the liver
amphipathic compounds
what stimulates contraction of the gall bladder/secretion of bile & secretion of pancreatic enzymes? what stimulates this?
CCK- secreted by the intestinal cells when stomach contents enter the intestine
food entering small intestine
why is cow milk not suitable for the development of a human child?
does not contain the long chain fatty acids that are essential for brain development
Function of Bicarbonate
what hormone causes its release, and from where
raises the pH of the contents of the intestinal lumen into a range (pH ~6) that is
optimal for the action of all of the digestive enzymes of the intestine.

*secretin signals liver, pancreases, and intestine to release it
function of colipase
Bile salts inhibit pancreatic lipase activity by coating the substrate and not
allowing the enzyme access to it. The colipase binds to the dietary fat and to the
lipase, relieving the bile salt inhibition and allowing triglyceride to enter the
active site of the lipase.
Pancreatic lipase is secreted along with another protein, __________, in response to the release of cholecystokinin from the intestine.
colipase
what do you think first when you see elevated pancreatic lipase in a pt? what is a common cause of this?
pancreatitis
alcohol

is the result of its escape from the inflamed
exocrine cells of the pancreas into the surrounding pancreatic veins.
how does the pancreas remove fatty acids (cholesterol esters) from compounds
how does it digest phospholipids to free fatty acids and lysophospholipid?
esterases
phospholipase A2
what activates phospholipase A2 from its zymogen form?
trypsin
what is necessary for the absorption of dietary lipids (lipid soluble vitamins, etc) in the lumen of the gut?
bile salt micelles
how much of bile is recirculated thru the enterohepatic circulation to the liver
95%
how does the absorption of short and medium chain fatty acids differ from the rest of the dietary lipids?
don't need bile salts for absorption. enter directly into intestinal epithelial cells and enter portal venous blood instead of lymph and end up traveling to the liver attached to albumin
what would you expect the cause of jaundice in a person with sickle cell anemia be? why can this be painful?
acute hemolysis overloads the liver with bilirubin. this can precipitate is gallstones. the pain is derived from spasm of the pancreatic duct being blocked.
what are two causes of steatorrhea?
malabsorption of fats (often from lack of pancreatic secretions)
insufficient bile salts
the major apoportein associated with chylomicrons as they leave the intestinal cells is ____. It is related to B-100 apoprotein synthesized in the liver that serves as a major protein of VLDL.
B-48

*A stop codon is generated that causes a protein to be produced in the intestine that is 48% of the size of the protein produced in the liver; hence, the designations B- 48 and B-100.
a typical chylomicron is made up predominantly of what?
TG

*also contain cholesterol and fat soluble vitamins

Within the intestinal epithelial cells, the fatty acids and 2-monoacylglycerols are condensed by enzymatic reactions in the smooth endoplasmic reticulum (ER) to
form triacylglycerols.
Why do TAGs have to be packaged into lipoprotein particles
If triacylglycerols entered the blood directly, they would coalesce, impeding blood flow.
The protein component of the lipoproteins is synthesized on the _________ ER. Lipids, which are synthesized in the ________ ER, are complexed with the proteins to form the chylomicrons.
rough
smooth
what is a "mature" chylomicron?
one that has accepted proteins from HDL within the lymph and blood
*initially they are called nascent (newborn) chylomicrons
least dense of the blood lipoproteins
chylomicrons
_____________ is an artificial fat substitute designed to allow individuals
to obtain the taste and food consistency of fat without the calories
from fat.
Olestra
*consists of a sucrose to which fatty acids are esterified to the hydroxyl groups.
*FA's attached to the sucrose are resistant to pancreatic lipase
*because Olestra has the ability to pass through the digestive system unimpeded, so it can also carry fat-soluble vitamins.
*cramping/diarrhea
What drug is used for weight loss by inhibiting the activity of pancreatic lipase?
orlistat

a chemically synthesized derivative of lipostatin, a natural lipase inhibitor found in certain bacteria.

*works in the intestinal lumen and forms a covalent bond with the active-site serine residues of
both gastric and pancreatic lipase, inhibiting them
What should individuals on orlistat make sure to do?
follow low fat diet to avoid GI distress
what two proteins are transferred to nascent chylomicrons from HDL
apoE
apoCII
how are chylomicrons recognized by the liver?
HDL transvers ApoE which allows recognition by the liver.
What tissues produce LPL
-adipose (this isozyme has higher Km than muscle)
-muscle cells (esp cardiac)
-lactating mammary gland
where is the primary location recognized by ApoCII
muscle and adipose

*activator of LPL that digests the triacylglycerols of the chylomicrons and VLDL in the blood.
what stimulates LPL release (mainly from adipose) to facilitate the hydrolysis of fatty acids from TGs?
insulin (after a meal)

to facilitate the hydrolysis of fatty acids from the triglyceride.
what does heparin bind to in order to stop clotting?
Binds and activates Antithrombin III which inhibits clotting factors
how is it that heparin can increase triglyceride content of the blood?
heparin binds LPL and dislodges it from the capillary wall
what does LPL do to a chylomicron?
turns it into a chylomicron remnant. this knocks most of the ApoC off exposing ApoE and promoting uptake by the liver
___ is recognized by membrane receptors, particulary those on surface of liver cells, allowing them to enter these cells by endocytosis for digestion by lysosomes.
ApoE inn chylomicrons
___ acts as an activator of LPL, the enzyme on capillary endothelial cells, which digests triacylglycerols of the chylomicrons and VLDL in the blood.
apoCII
How are FA's released by LPL transported
forming complexes with albumin
Why does muscle LPL have a lower Km than adipose
Thus, muscle cells can obtain fatty acids from blood
lipoproteins whenever they are needed for energy, even if the concentration of
the lipoproteins is low.
what happens to chylomicron remnants after LPL action?
The remnant has lost many of the apoCII
molecules bound to the mature chylomicron, which exposes apoE.
This remnant binds to ApoE receptors on hepatocytes

The products of lysosomal digestion (e.g., fatty acids, amino acids, glycerol, cholesterol, phosphate) can be reused by the cell.
Function of heparin
anticoagulant because it binds to antithrombin III
(ATIII), and the activated ATIII then binds factors necessary for clotting and inhibits them from working.
Effect of heparin on LPL and TG's
Since LPL is bound to the capillary endothelium through binding to proteoglycans, heparin also can bind to LPL and dislodge it from the capillary wall.

This leads to loss of LPL activity and an increase of triglyceride content in the blood.
Gallstones obstruct common bile ducts & cause increased serum bilirubin levels causing (direct or indirect) hyperbilrubinemia
direct (conjugated bilirubin)

*bilirubin flows back innto venous blood draining from liver
Microsomal triglyceride transfer protein (MTP) is needed for ____
assembly of chylomicrons w/in ER of enterocyte

*accelerates the transport of triglycerides, cholesterol esters, and phospholipids across membranes of
subcellular organelles

*binds to B- apolipoproteins- As the
protein is being translated, lipid (a small amount of triglyceride) begins to associate with the protein, and the lipid association is catalyzed by MTP.
Symptoms of abetalipoproteinemia
- lipid malabsorption (and its accompanying symptoms such as steatorrhea and vomiting), which can result in caloric deficiencies and weight loss
- sx associated w/ deficiencies in lipid-soluble vitamins
Why can't MTP inhibitors be used in lowering lipids and cholesterol levels in patients?
Although the inhibitors are effective in lowering lipid levels, they also initiate severe hepatic steatosis (fatty liver), which could lead to liver failure (Due to inability to form VLDL and export TG's)

*current research is aimed at targeting the intestinal MTP without affecting the hepatic MTP
Bile salts must reach a particular concentration within the intestinal lumen before they are effective agents for lipid digestion. This is because of which one of the following?
A. The bile salt concentration must be equal to the triglyceride
concentration.
B. The bile salt solubility in the lumen is a critical factor.
C. The ability of bile salts to bind lipase is concentration-dependent.
D. The bile salts cannot be reabsorbed in the ileum until they reach a certain concentration.
E. The bile salts do not activate lipase until they reach a particular
concentration.
B. The bile salt solubility in the lumen is a critical factor.
The absence of which hormone listed would result in an inability to raise the pH of the partially digested food leaving the stomach, leading to an inability to digest lipids in the intestine?
A. Pancreatic lipase
B. Intestinal cholecystokinin
C. Pancreatic cholecystokinin
D. Intestinal secretin
D. Intestinal secretin
Short- and medium-chain fatty acids in the diet follow which one of the following digestive sequences?
A. They are emulsified by bile acids.
B. They are packaged in micelles.
C. They enter the portal blood after intestinal absorption.
D. They enter the lymph after intestinal absorption.
E. They are formed by chylomicrons.
C. They enter the portal blood after intestinal absorption.
A patient has been taking an experimental drug to reduce weight. The drug leads to significant steatorrhea and some night-blindness. A potential target of this drug is which one of the following?
A. LPL activity
B. Albumin synthesis
C. Glucagon release
D. Insulin release
E. Cholecystokinin release
E. Cholecystokinin release

*can occur bc of mutations in lipase or colipase, or inability to release CCK. In absence of CCK, the digestive enzymes from the pancreas (including lipase and colipase) will not be secreted to the intestine, nor will bile acids be secreted from the gallbladder to the intestine.
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