Transcript Digestion of Fats (Triglycerides/Lipids)

Digestion of Fats
(Triglycerides/Lipids)
By: Brittany Speer, William McNees, Peter Schulz, Maiko Ibay, and
Regina Tabi
Chemical Structure of Fat
Lipid is the general term which encompasses all
different types of fat
Lipids are further broken down into saturated and unsaturated
A Triglyceride molecule is made up of one glycerol
molecule and three fatty acid chains
Saturated
The fatty acid chain consists of only single bonds, thus fully
saturated with hydrogens
Unsaturated
Mouth
The mouth is the first site of mechanical and chemical digestion
Mechanical Digestion
Physical Breakdown of food
Occurs through the teeth, tongue, and palate
Food is mixed with saliva to create a bolus
No chemical digestion occurs in the mouth
Esophagus
Connects the pharynx to the stomach
Responsible solely for motility
Peristalsis
Rhythmic, wave-like contractions that moves food through the digestive tract
Moves the bolus at a rate of 2-4cm per second
Food is emptied into the stomach through the gastroesophageal sphincter
Constriction of this sphincter prevents stomach contents from regurgitating into the esophagus
Stomach
Functions of the stomach
Storage of food
Kill bacteria with the strong acidity of the
gastric juices
Contractions of the stomach cause the
stomach to churn and mix the food
substances with the gastric juices
This combination is called chyme
Continuation of mechanical digestion
Small Intestine
Chemical digestion of fats begins in the small intestine
Chyme enters the upper portion of the small intestine called the duodenum
This causes the gallbladder to contract and secrete bile into the duodenum through the bile duct
The pancreas then secretes bicarbonate ions and enzymes
Bicarbonate ions neutralize the pH of the chyme
Emulsification by Bile Salts
Bile salts are synthesized in the liver using
cholesterol and regulated by bacteria
Stored in the gall bladder
Once secreted into the duodenum the bile salts
surround the fat and break it into smaller
droplets
Surrounding the smaller droplets prevents the fat from
reclumping
Increases the surface area for the lipase to act upon the
fat droplets
Digestion by Enzymes
Pancreatic Lipase digests triglycerides into its individual
parts
Long Chain fatty acids (>10 carbons): breaks down into a
monoglyceride and two free fatty acids
Short Chain fatty acids (<10 carbons): breaks down into glycerol
and three free fatty acids
Pancreatic Colipase
Colipase is a protein co-enzyme that is required for optimal
activity of pancreatic lipase
Secreted by the pancreas in its inactive form and activated by
trypsin in the duodenum
Absorption
● Most fat absorption takes place in the duodenum or jejunum – micelles carry monoglycerides and free fatty
acids to the brush border where they diffuse into enterocytes
● Bile salts are absorbed in the ileum (enterohepatic circulation)
● Once in the enterocytes, monoglycerides and free fatty acids are reformed into triglycerides
● The triglycerides, cholesterol, phospholipids, and protein carriers form LIPOPROTEIN
Once these lipoproteins leave the cell, they become
CHYLOMICRONS and enter the lymph system
MCTs, short-chain fatty acids and glycerol are absorbed
directly into bloodstream. They do not enter the lymph
system.
Small lipid fragments:
● Glycerol and short chain FAS (SCFAS)
● Absorbed directly into the bloodstream
● Portal vein to liver
Big lipid fragments:
● Monoglycerides and LCFAs need help!
If absorbed into the blood, they need to be emulsified
Cholesterol
Cholesterol and other sterols are poorly absorbed. Overall, about 50% of dietary
cholesterol is absorbed.
Dietary fat increases cholesterol absorption
Fiber (especially soluble fiber) and phytosterols decrease cholesterol absorption
High levels of low-density lipoprotein (LDL) cholesterol in the circulation increase the
risk for the development of atherosclerosis
Of the total cholesterol that passes through the small intestine, only half is typically
absorbed, and the rest is eliminated in the feces.
Cholesterol Biosynthesis Pathway
The process to form the 27 carbon compound of
cholesterol occurs primarily in 4 main stages.
Stage 1: Synthesis of mevalonate from acetate
Two molecules of acetyl-CoA condense, forming
acetoacetyl-CoA, which condenses with a third
molecule of acetyl-CoA to yield the six-carbon
compound β-hydroxy-β-methylglutaryl-CoA (HMGCoA), which is then reduced to from mevalonate
Generally takes place in the endoplasmic reticulum of hepatic cells!
Cholesterol Biosynthesis Pathway
Stage 2: Conversion of mevalonate to two activated isoprenes
In this next stage, three phosphate groups are transferred from
three ATP molecules to mevalonate., The phosphate attached to
the C-3 hydroxyl group will leave and produce a double bond in
the 5 carbon product.
The two isoprenes are Δ3-isopentenyl pyrophosphate and dimethylallyl
pyrophosphate
Cholesterol Biosynthesis Pathway
Stage 3: Condensation of six activated isoprene units
to form squalene
Isopentenyl phosphate and dimethylallyl phosphate undergo
a “head-to-tail” condensation in which one phosphate group
is displaced and a 10-carbon chain (geranyl phosphate) is
formed.
Another “head-to-tail” condensation→ 15-carbon farnesyl
pyrophosphate
Finally, two molecules of farnesyl join head to head,
eliminating the phosphate groups and forming squalene
Cholesterol Biosynthesis Pathway
Step 4: Conversion of squalene to the four-ring steroid
nucleus
Squalene monooxygenase adds one oxygen atom from
O2 which forms squalene-2,3-epoxide.
Linear squalene epoxide can be converted into a cyclical
structure→
Lanosterol (in animal cells)→ converted into cholesterol
in a series of about 20 reactions
Cholesterol Ester
It is an ester of cholesterol
Ester: chemical compound in which at least one hydroxyl
group replaced by an alkyl group
The ester bond is formed between the carboxylate group of
a fatty acid and the hydroxyl group of cholesterol
Lower solubility in water due to their increased
hydrophobicity
More cholesterol can be packaged in lipoproteins in this
structure, so the body does this to be more efficient→
inactive transport form
Lipoprotein Structure
● Membrane:
○ Single phospholipid layer
○ Protein
○ Cholesterol
● Core:
○ Triglyceride
○ Cholesterol ester
● Differences in various lipoproteins:
Transportation of Lipids in Blood
Chylomicrons:
● Phospholipids, cholesterol and triglycerides (resynthesized in E.R. of enterocytes)
combine with protein to form chylomicrons
● 90% triglyceride, 4% phospholipid, 1% protein, 5% cholesterol
○ apo E
● Excreted into lacteals and circulate into the blood via
thoracic duct
○ (lacteals -> lymphatic vessels -> thoracic duct -> left subclavian vein)
● Acquire apolipoprotein (Apo E)
Transportation of Lipids in Blood
Chylomicrons:
● Lipoprotein lipase enzyme hydrolyze triglycerides held within chylomicron
● Free fatty acids bind to albumin and circulate in plasma to be used by skeletal
muscle and adipose tissue
● Remnant particles are released and circulate until taken
up by liver
Transportation of Lipids in Blood
Very Low-Density Lipoprotein (VLDL)
● 60% triglyceride, 18% phospholipid, 8% protein, 14% cholesterol
○ apo B-100, apo C1, apo E -> picks up apo C-II and additional apo E during circulation
● Deliver endogenously produced triglycerides to extrahepatic cells
● Cholesterol and triglycerides produced in liver combine with other
apolipoproteins to form VLDLs
● VLDLs circulate and bind to capillary cells, losing triglycerides along the way via
receptor-mediated endocytosis
Transportation of Lipids in Blood
Low-Density Lipoprotein (LDL)
● 10% triglyceride, 20% phospholipid, 25% protein, 45% cholesterol,
○ apo B-100
● Product of VLDL losing triglycerides
● Delivers endogenous cholesterol to various organs before returning to liver
● Contributes to atherosclerosis
● Familial Hypercholesterolemia
● Dyslipidemia (Hyperlipidemia)
Transportation of Lipids in Blood
High-Density Lipoproteins (HDLs)
● “Reverse Cholesterol Transport”
● 5% triglyceride, 30% phospholipid, 45% protein, 20% cholesterol
○ apo A-1 & apo A-2
● Produced in peripheral tissues
● HDL binds to receptors in vessel walls of extrahepatic tissue
● Lecithin-cholesterol acyltransferase (LCAT) converts free cholesterol in
cholesterol ester, which moves into center of HDL particle
“Good” vs. “Bad” Cholesterol
● Cholesterol transported by LDL and HDL is the same
Short Chain and Long Chain Fatty Acids
Short-chain fatty acids:
Fatty acids with fewer than 6 carbon atoms that are only produced by bacterial fermentation of
polysaccharides that resist digestion in the small intestine (e.g. dietary plant matter) and can enter
the colon
Stimulates active Na+ and Cl- absorption to promotes water reabsorption by osmosis and
therefore retain calories and electrolytes
Can be used for energy by epithelial cells in the colon and the central nervous system (can pass
through BBB)
Can be absorbed through the portal vein into the blood
E.g. Acetate, Propionate, and Butyrate
Short-Chain and Long-Chain Fatty Acids
Long-chain fatty acids
Fatty acids with 14 or more carbons and are the
building blocks of lipids or fats
Found in most fats and oils and cannot cross the BBB
Because they cannot be absorbed directly into the
blood, they are reassembled into triglycerides and
packaged into chylomicrons.
The chylomicron is released into a lacteal, a lymphatic
capillary within the small intestine, -> lymphatic
system -> thoracic duct -> left subclavian vein (into
blood) -> wherever they need to go
Omega-3 and Omega -6 Fatty Acids (Essential Fatty Acids)
The body needs minimal amounts of molecules for its own
anabolic reactions (synthesis reactions)
However, there are some molecules (e.g. essential fatty
acids) that cannot be synthesized within the body and
must be obtained through diet
Omega-3 Fatty Acids: (n-3)
Polyunsaturated fatty acids that have their first
double bond on the 3rd carbon from the methyl
end (-CH3)
Alpha-linolenic acid (ALA): found in oily fish has
18 carbons, but it has three double bonds, with
its first double bond on the 3rd carbon from the
Omega-3 and Omega -6 Fatty Acids
Omega-6 Fatty Acids: (n-6)
Polyunsaturated fatty acid that has its first double bond on the sixth carbon from the methyl end.
Linolenic acid: found in corn oil, contains 18 carbons with 2 double bonds,
Mammals lack enzymes to insert this double bond at the n-6 or n-3 positions and
must eat linolenic acid and alpha-linolenic acid
Studies have suggested that omega-3 fatty acids offer protection against
cardiovascular disease-- inhibit platelet function in thrombus formation and the
Statins and HMG-coenzyme A reductase
Statins are lipid-lowering drugs, also known as HMG-CoA reductase inhibitors
People with dangerously high LDL cholesterol concentrations take these drugs
Function:
E.g. Lipitor
Inhibits enzyme HMG-Coenzyme A reductase-HMG-coenzyme A reductase: integral protein of
endoplasmic reticulum membranes that catalyzes the
rate-limiting step in cholesterol synthesis (Mevalonate
pathway), binds HMG-CoA
Statins structurally similar to HMG-CoA and can compete
for its active site
Decreases the ability of the liver to produce its own cholesterol
which stimulates production of LDL receptors which then
Questions?