KAAP221 Lecture Notes - Lecture 21: Lipoprotein Lipase, Pancreatic Lipase Family, Bile Acid

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Lecture 21
Lipid digestion
Begins in mouth - mechanical breakdown; and chemical digestion with lingual lipase (limited in
adults)
Continues in stomach - mixing of chyme; lingual lipase is minimally active
Complete in duodenum (most significant area of lipid digestion) - CCK released, which triggers
release of pancreatic lipase; bile enters duodenum and breaks apart large lipids into smaller
droplets - emulsification; micelles are formed (lipid bile-salts)
Lipid absorption and transport
Micelles contain digested lipids and bile salts
Micelles migrate towards brush border, comes into contact with brush border, and the lipid
products of digestion diffuse into the epithelial cell; then the bile salts are released and
reabsorbed in the ileum and we recirculate that
Cells make new TG’s from the absorbed lipids
The intestinal cells now secrete these new TG’s that have joined with other types of lipids such as
sterols and form a chylomicron; chylomicron exits via exocytosis from the epithelial cells; these
diffuse into the lacteals (lymphatic capillaries specific to GI tract), then transport through the
lymphatic system, make their way into the thoracic duct, and go to the L subclavian vein
Capillary walls contain lipoprotein lipase, which can break down chylomicrons and releases fatty
acids and monoglycerides that can diffuse into interstitial fluid and be utilized by cells
Lipid utilization
Skeletal muscle - use FA’s to generate ATP for contraction and to convert glucose to glycogen
Adipose tissue - uses FA’s and monoglycerides to synthesize TG’s for storage
Liver - absorb intact chylomicrons; extracts TG’s and cholesterol
Liver processing of lipids
Liver removes TG’s from absorbed chylomicrons, add cholesterol, and alters surface proteins to
form a VLDL, or LDL
Creates LDL’s and very low density lipoproteins (VLDL’s)
VLDL’s transport TG to muscle and adipose tissue - VLDL’s tend to be more TG-rich
LDL’s deliver cholesterol to peripheral tissues - LDL’s tend to be more cholesterol-rich
Cells extract and use cholesterol to build membranes, hormones, and other materials
HDL
Proteins released by liver
Absorb excess cholesterol form the bloodstream and return it to the liver
This cholesterol can be extracted, packaged in new LDL or VLDL, or be excreted in bile salts
Lipids
Application to health
Lipid panels are commonly run in patients
Can be indicators of potential CV problems
Total chol > 200 mg/dl - at risk
High LDL:HDL ratio - at risk
Excess cholesterol can accumulate as plaques in blood vessels, causing heart attacks and strokes
Lipid catabolism
Lipolysis = lipid catabolism
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Lysosomal enzymes break down TG’s into
1 glycerol molecule - can be converted to pyruvate in glycolysis
3 FA molecules
FA’s are catabolized to acetyl-CoA through beta-oxidation; with beta-oxidation, add a CoA to the
end of the FA and chop off 2 C’s in, so 2 C’s with a CoA, and continue so you have a bunch of 2
C’s with CoA’s attached
More efficient than glucose metabolism
6-C glucose yields 30-32 ATP
6 carbons from FA’s yield 39-40 ATP (most FA’s are 18 C’s, so about 120 ATP)
Lipid synthesis - anabolic
Lipogenesis = synthesis of lipids
Begins with acetyl-CoA - lipids, AA’s, and carbs can be converted
Some FA’s synthesized from acetyl-CoA - involves a series of enzymatic steps different from beta-
oxidation, using different enzymes
There are two essential FA’s that cannot be synthesized from lipogenesis; must be consumed in the
diet; these are linolenic acid (in the family of omega 3) and linoleic acid (in the family of omega
6)
Many structural and functional lipids created from FA’s within the cell
Glycerol can be synthesized from intermediate products of glycolysis within the cell
3 FA’s + glycerol = TG
Lipid catabolism and synthesis
Important in the diet because they serve as energy reserves
Useful because - beta-oxidation is very efficient; and excess lipids can be easily stored as TG’s
However
They cannot provide large amounts of ATP quickly compared to glycolysis
Difficult for water-soluble enzymes to access the insoluble droplets
Well suited for chronic energy demands during stress or starvation
Protein digestion
Mouth - only mechanical processing
Stomach - mechanical processing; and chemical processing - proteins are denatured, pepsin and
HCl
Duodenum
CCK stimulates pancreatic enzymes
Enteropeptidase convert trypsinogen to trypsin
Trypsin activate other pancreatic proenzymes to their active forms
Protein absorption and transport
Short peptides and AA’s are absorbed into epithelial cells of the SI by - facilitated diffusion (with
carrier protein) and cotransport
Released from epithelial cell basal surface through same cell transport mechanisms
These epithelial cells have first dibs on the AA’s because they see them first
AA’s transported to liver through intestinal capillaries to hepatic portal vein
In liver
Control of plasma AA levels is less precise than glucose - can increase after protein-rich meal
Liver uses AA’s to - synthesize plasma proteins and create 3-C molecules for gluconeogenesis
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Document Summary

Absorb excess cholesterol form the bloodstream and return it to the liver. This cholesterol can be extracted, packaged in new ldl or vldl, or be excreted in bile salts. Vldl"s transport tg to muscle and adipose tissue - vldl"s tend to be more tg-rich. Ldl"s deliver cholesterol to peripheral tissues - ldl"s tend to be more cholesterol-rich. 1 glycerol molecule - can be converted to pyruvate in glycolysis. They cannot provide large amounts of atp quickly compared to glycolysis. Control of plasma aa levels is less precise than glucose - can increase after protein-rich meal. Liver uses aa"s to - synthesize plasma proteins and create 3-c molecules for gluconeogenesis: aa synthesis, 20 aa"s - 10 are nonessential (produced by liver and body cells) and 10 are essential (need to be consumed in diet) Defined as minimum resting energy expenditure of awake, alert person. Bmr can be measured directly by monitoring respiratory activity (o2 consumption, co2 production)

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