GI-Biochem- Digestion & Absorption of Lipids- Wells Flashcards
◦ Free fatty acids are/are not part of the diet
are not
Those are products of digestion
What matters more? The type of fat (form) or the amount?
fat form
◦ Role of sphingolipids from the diet is unclear
◦ Relatively small amounts are consumed
◦ Research suggests sphingolipids are degraded to other prior to entry into the bloodstream
products
Dietary cholesterol has little/much influence on plasma cholesterol?
little
Humans cannot synthesize fatty acids containing cis double bounds beyond what position from the end carbon?
9
Arachidonic Acid is a precursor for what two substances?
prostaglandins and leukotrienes
Which two fatty acids are essential?
Which lipid is a storage form of energy and a major macronutrient?
Triacylglycerol (TAG)
What unsaturated liquid fats are made creamy through industrial hydrogenation.
◦ e.g. margarine
trans-fats
Margarine behaves like saturated fat despite the double bond.
What effect does trans fat have on LDL, HDL, and disease or disease prevention?
What effect does saturated fatty acid have on LDL, HDL, and disease or disease prevention?
What effect does monounsaturated fatty acid have on LDL, HDL levels and disease and/or disease prevention?
What effect does omega 6 have on LDL and HDL levels, and incidence of coronary heart disease?
What effect does omega 3 have on LDL, HDL levels and disease and/or disease prevention?
plasma cholesterol does/does not correlate with negative health outcomes and dietary cholesterol does/does not correlate with plasma cholesterol
does
does not
What 4 diseases processes are affected by increasing plasma cholesterol levels?
- Heart disease
- Malignant neoplasms (all forms)
- Stroke
- Diabetes mellitus
◦Dietary cholesterol is/is not interrelated to body’s cholesterol production.
◦ Dietary cholesterol levels do/don’t relate strongly to blood levels.
◦ Levels of de novo cholesterol production will/will not compensate.
◦ Per day: 1000mg produced in liver vs. 300mg from diet.
◦ Genetics matter more/less for heart disease risk.
is
don’t
will
more
Phospholipases are in control of lipid
digestion
Review summary of digestion
Phospholipases degrade chain fatty acids
short
Which lipoprotein contains apolipoproteins, A-IV, A-I, A-V, B48, and is mostly filled with triglycerides?
chylomicron
Which lipoprotein class contains B100, E, C, and is mainly filled with triglycerides?
VLDL
Which lipoprotein consists of apolipoprotein B100 and is filled with cholesteryl esters?
LDL
Which lipoprotein is consists of A-I, E, A-II, and is filled with chlesteryl esters and is the smallest?
HDL
What are the plant cholesterol mimics and have beneficial health effects associated with steroid/hormones menopause and also lower blood cholesterol by limiting amount available to body?
phytosterols
act as a negative regulator and signals the body to make less cholesterol
What process occurs in the small intestine, involves bile, and breaksdown long chain fatty acids?
emulsification
What are the 2 main goals of emulsification?
- -Increased surface area and apply mechanical force for breakdown
- -Sets up enzyme access for digestion
How does emulsification increase surface area?
by breaking down the long chain fatty acids into smaller more manageable fragments
Bile is created in the and stored/released by the .
liver, gallbladder
Bile is mainly composed of .
bile salts
What are other components of bile other than bile salts?
◦ Bile Salts (61%)
◦ Fatty acids (12%)
◦ Cholesterol (9%)
◦ Proteins (7%)
◦ Phospholipids (3%)
◦ Bilirubin (3%)
◦ Others (5%)
Emulsification of dietary lipids is the combination of what two complementary actions:
- mechanical agitation
- secretion of bile salts
Emulsification promotes the production of increasingly smaller/larger particles, resulting in increased accessibility of lipids to digestive enzymes.
smaller
Bile salts: -made in the liver - stored in the gallbladder - secreted to the
- have properties that particles
as they become smaller, prevent them from coalescing
small intestine
detergent
stabilize
Colic acid, derived from cholate, is one of two major acids that are part of
.
bile
The 2 major regulating hormones for lipid digestion are:
cholecystokinin
secretin
Secretin stimulates what from which organs?
Bicarbonate and pancreatic enzymes from pancreas
bile form gallbladder
What is the role of cholecystokinin in digestion?
inhibits gastric motility
stimulates secretion of pancreatic enzymes from pancrease and bile from gallbladder
TAG digestion: TAG is too big/small for intestinal mucosal cells to endocytose efficiently
big
What enzyme is being described:
- an esterase, cleaves fatty acids at carbon-1 and -3, products:
2-monoacylglycerol, free fatty acid
- represents 2 to 3% of total protein in pancreatic secretions
- has high catalytic efficiency
pancreatic lipase
What is the job of colipase and what is its ratio to pancreatic lipase?
it is a cofactor for pancreatic lipase with a ratio of 1:1
How does colipase function as a cofactor for pancreatic lipase?
to anchor pancreatic lipase at the lipid-aqueous interface to promote pancreatic lipase enzymatic activity when inhibitory bile acids are present
dietary cholesterol is present in two forms [85-90% (free) and 10-15% (cholesteryl ester)]
non-esterified
esterified
What is the enzyme that digests esterified cholesterol (cholesteryl ester)?
pancreatic cholesterol esterase
What promotes cholesterol esterase activity?
- bile salts
What happens when cholesterol esterase works on cholesterl ester?
- producing cholesterol and free fatty acids
- all cholesterol is finally non-esterified
- increases SA
Phospholipid digestion: ingested phospholipids are digested by removal of fatty acids by different pancreatic enzymes, producing two fatty acids and one glycerylphosphoryl base
sequential
two
What are the two pancreatic enzymes that digest phospholipids?
Phospholipase A2
Lysophospholipase
Which of the two phospholipid digesting enzymes is being described:
- removes the fatty acid from position 2 to produce a lysophospholipid and a free fatty acid
Phospholipase A2
Which of the two phospholipid digesting enzymes is being described:
-removes the fatty acid from position one to generate one fatty acid and one glycerylphosphoryl base
Lysophospholipase
After the breakdown of the phospholipids by pancreatic enzymes, Phospholipase A2 and Lysophospholipase,
- glycerylphosphoryl bases can be , further digested or excreted in the
absorbed
feces
Control of lipid digestion:
o pancreatic secretion of hydrolytic enzymes and bile is controlled by a small peptide hormone,
o CCK is released from cells of the lower duodenum and jejunum in response to the presence of lipids and partially digested proteins.
cholecystokinin (CCK)
mucosa
- CCK causes contraction of the and secretion of bile: a mixture of bile salts, phospholipids and free cholesterol
- CCK causes cells of the pancreas to secrete hydrolytic enzymes
gallbladder
exocrine
CCK also acts to decrease/increase gastric motility, reducing release rate of gastric contents to the small intestine
decrease
What digestive hormone is being described:
o Small peptide hormone
o Produced by other intestinal cells other than enterocytes
o A response to the low pH of intestine entry chime
o Promotes release of bicarbonate-rich solution from the liver and pancreas into the small intestine
o Provides the appropriate pH for optimal pancreatic enzyme function
Secretin
Sectretin promotes release of bicarbonate-rich solution from the and into the small intestine
liver
pancreas
What is the basic structure of a micelle and what is the purpose of its formation?
non-polar inside
polar outside
bile salts, phospholipids, colipase, and pancreatic lipase around the core
increase SA for faster/easier breakdown
What are 6 things that chylomicrons contain:
Apoliporotein B-48, B-100
fat soluble vitamins
triacylglycerol
cholesteryl ester
phospholipids
cholesterol
What is the most abundant substance in a chylomicron?
triacylglycerol
are key transporters of lipids throughout lipid metabolism in the body
Lipoproteins
Liproprotein occurs in different lengths (48 vs. 100) due to editing
RNA
What is a disease that cannot regulate fat storage?
apolipoproteinemia
Explain the journey of chylomicrons throughout the body?
formed at the intenstinal epithelial cell
move into lymph to the blood
travels to and used in muscle and for fat storage in adipose tissue
remnants travel to liver for resynthesis
HDL is generated by
and
with high/low cholesterol to the lowest/highest TAG
liver
intestine
lowest TAG
high cholesterol
What lipoprotein is being described?
Delivers cholesterol from the peripheral tissues to the liver for elimination
HDL
VLDL is generated in the and has a high/low TAG level and high/low cholesterol level.
liver
high TAG
low cholesterol
Which lipoprotein is being described?
Delivers endogenous TAG to peripheral tissues
VLDL
generates LDL which is composed of high/low TAG and the highest/lowest cholesterol
VLDL
low TAG
the highest cholesterol
The generates Chylomicrons which are composed of the
highest/lowest TAG and the highest/lowest cholesterol
Which lipoprotein is being described?
Deliver dietary (exogenous) TAG to the peripheral tissues
chylomicrons
◦Microsomal triglyceride transfer protein (MTP)
◦ Small intestine Transfers lipid to as it is produced
◦ Small intestine Transfers lipid from the to the ER lumen (IIj) 39
◦ Liver function: transfer to
◦ Intestine function: transfer to
apoB-48
cytoplasm
VLDLs
chylomicrons
What disease appears in the first few months of life, include failure to gain weight and grow at the expected rate; diarrhea; abnormal star-shaped red blood cells and fatty, foul-smelling stools that may contain large chunks of fat and/or blood. Later in childhood impairment of the CNS function, poor muscle coordination, progressive retina degeneration to near-blindness (due to deficiency of vitamin A, retinol)?
Abetalipoproteinemia (Bassen-Kornzweig syndrome)
Abetalipoproteinemia (Bassen-Kornzweig syndrome)
o in the Microsomal TAG-transfer protein (MTTP or MTP)
o Autosomal – rare (~ 100 cases described)
o Near complete absence of the -containing lipoproteins
o Affects the absorption of dietary fats, cholesterol, and fat-soluble vitamins (A, D, E, K)
Defect
recessive
Apo B
What disease process is being described?
◦ Lipid malabsorption
◦ Results in increased lipid, fat-soluble vitamins, and essential fatty acids in feces
◦ Causes: lipids digestion/absorption disturbances from conditions like:
- Cystic fibrosis (causing poor digestion)
-Short bowel syndrome (causing decreased absorption)
Steatorrhea
excess lipids in feces
How to treat steatorrhea or conditions that cause steatorrhea?
Short- and medium- chain fatty acids are important in nutrient therapy for individuals with malabsorption disorders
What are 3 causes of steatorrhea:
◦ Cystic fibrosis (causing poor digestion)
◦ Short bowel syndrome (causing decreased absorption)
exocrine pancreatic insufficiency
Gallstones can also obstruct the common bile duct, causing to backflow into blood draining from the liver. In this manner, bilirubin levels increase. The eyes take up this pigment and look jaundiced. Inflammation from a cystic duct obstruction and cholecystitis can also cause analogous, but milder, symptoms.
bilirubin
venous
may result from sickle-cell anemia, which is caused by increased/decreased red blood cell destruction in the spleen and an inability of the liver to conjugate all the available resulting from heme degradation.
Cholecystitis
increased
bilirubin
◦ Pancreatitis may result from alcohol abuse
◦ Leads to problems within the intestine
chronic
malabsorption
The drug is a chemically synthesized derivative of lipostatin, a natural lipase found in certain bacteria. The drug works in the intestinal lumen and forms a covalent bond with the active site serine residues of both gastric and pancreatic, inhibiting their activities.
orlistat
inhibitor
lipase
excessive nondigested fat in the intestines can lead to GI from excess gas formation.
distress
(like from using orlistat)
◦ 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
◦ Night-blindness results from lack of fat-soluble vitamin A absorption caused by defects in lipase, colipase, or defects in release of cholecystokinin. 48
Chylomicrons and VLDL contain overlapping sets of apolipoproteins. The apolipoproteins B-48 and B-100 are similar with respect to which one of the following?
◦ A) They are synthesized from the same gene. ◦ B) They are derived from alternative splicing of the same hnRNA. ◦ C) Apo B-48 is a proteolytic product of Apo B-100. ◦ D) Both are found in mature chylomicrons. ◦ E) Both are found in VLDL.
◦ A) They are synthesized from the same gene.
◦ ApoB-48 and apoB-100 are both derived from the apoB gene, through mRNA editing.
