2. Absorption of lipids
The end products of lipid digestion are
Fatty acids
Glycerol
2-Monoacylglycerol
1- Mono acylglycerol
Cholesterol
Lysophonpholipid
3. Stomach
gastric
mobility -
Small
Hormonal control
intesti cholecytokinin
ne
+
Gut
Endocrine
cells
Dietary (enlarged)
lipids +
bicarbonate Secretin
sec (in blood)
re
Pancreatic tes
lipase secret +
e s
pancreas
bile secret +
e s
Degradation of
dietary lipids Gall bladder
4. As food enters the intestine, cholecystokinin hormon is
released which signals (1) the gallbladder to release bile salts
and; (2) the exocrine (pancreas) to release digestive
enzymes.
Within the intestine, bile salts emulsify fats, which increase
their accessibility to pancreatic lipase.
4
6. Bile salts are synthesized in the liver, stored in the gallbladder,
secreted into the small intestine, resorbed in the ileum, and
returned to the liver via the enterohepatic circulation.
Under normal circumstances, 5% or less of luminal bile salts
are excreted in the stool.
6
7. Figure: Enterohepatic
circulation.
The bile salts
are reabsorbed
farther down the
intestinal tract and
returned to the
liver by the
enterohepatic
circulation.
7
8. Fate of dietary lipids:
TGs: FFA + glycerol
FFA:
- FFA from TGs muscle (energy production)
adipocytes( re esterified to TGs)
Glycerol : Glycerol from TGs in liver forms glycerol 3 phosphate ( glycolysis,
gluconeogenesis)
Chylomicron remnants:
Endocytosed into liver and are hydrolysed to their component parts and recycled by
the body.
- If this process is decreased due to impaired binding to the receptor on liver, they
accumulate in the plasma leading to type III hyperlipoproteinemia
9. 2-monoacylglycerols are reacylated to TAG via the
monoacylglycerol pathway.
(1) Glycerol released in the intestinal lumen is not reutilized
but passes into the portal vein; (2) glycerol released within the
epithelium is reutilized for TAG synthesis via the normal
phosphatidic acid pathway.
9
10. Monoacylglycerols are poor substrates for hydrolysis, so it
mean less than 25% of ingested TAG is completely hydrolyzed
to glycerol and FAs.
Because the micelles are soluble, they allow the products of
digestion to be transported through the aqueous environment of
the intestinal lumen and permit close contact with the brush
border of the mucosal cells, allowing uptake into the
epithelium.
10
11. TAG are further degraded to 2-monoacylglycerols and FAs as
the major end products of luminal TAG digestion.
Bile salts formed in the liver and secreted into the bile, permit
emulsification of the products of lipid digestion into micelles
together with phospholipids and cholesterol from the bile.
11
12. Micelles are formed within the intestinal lumen and interact
with the enterocyte (intestinal absorptive cells) membrane.
Lipid-soluble components diffuse from the micelle into the
enterocytes.
12
15. The intestinal epithelial cells resynthesize TAG and package
them into nascent (new) chylomicrons for release into the
circulation.
Long-chain FAs are esterified to yield to TAG in the mucosal
cells and together with the other products of lipid digestion,
secreted as nascent chylomicrons into the lymphatics, entering
the bloodstream via the thoracic duct.
15
16. Short- and medium-chain FAs are mainly absorbed into the
hepatic portal vein as FAs.
Cholesterol is absorbed and dissolved in lipid micelles, and is
mainly esterified in the intestinal mucosa before being
incorporated into chylomicrons.
Unesterified cholesterol and other sterols are actively
transported out of the mucosal cells into the intestinal lumen.
16
20. Packaging for transport
Lehninger et al., apolipo-
3rd ed., Fig. 17-2 proteins
chylomicrons
Particles for
transport of lipids
PL
to liver &
adipocytes
Size: 0.1–1 µm
Average
composition:
TG (84%)
chol (2%)
cholE (4%)
PL (8%) apolipoproteins (2%)
chol PL
cholE, TG
21. Summary of lipid
oil
digestion & absorption
drop
Enterocyte
lipase-
colipase MG 4ATPs/TG
FA TG
emulsion (>10C) apolipoproteins
TG
droplet MG phospholipids
FA
BILE
SALTS
lipase-
colipase chylomicron chylomicron
FA
mixed (<12C) FA
BILE albumin
micelle BILE
SALTS
SALTS
18
22. Lipids Are Transported in the Plasma as
Lipoproteins
Four Major Lipid Classes Are Present in
Lipoproteins.
Plasma lipids consist of TAG (16%), phospholipids (30%),
cholesterol (14%), and cholesteryl esters (CE) (36%) and a
much smaller fraction of unesterified long-chain FAs (4%).
22
There are three main points of regulation for cholesterol absorption into the body. When the micellar particle comes in the proximity of an enterocyte, cholesterol is transported into the enterocyte through a channel recently identified as NPC1L1. A fraction of this cholesterol is pumped back out of the enterocyte into the intestinal lumen by the complex ABCG5/G8, and the remainder is esterified by the enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT) into cholesteryl esters. Reference: Altmann SW, Davis HR Jr, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M, Wang L, Murgolo N, Graziano MP. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 2004;303:1201-1204.
Versions of lipoproteins where the core is the non polar material, triglyceride predominantly. 84% on average, with smaller amounts of other lipids and phospholipid primarily being at the surface acting as surfactant along with the proteins. Several proteins that have these code names, collectively known as apolipoproteins, protein part of a particle known as lipoproteins. Protein constitutes only a small fraction
Summary of lipid digestion and absorption. Pics not proportional. Begin with oil drop, and the early stages of digestion produce smaller particles, oil drop contains the lypitic material, triglycerides cholesterol esters in small amounts. The early digestive process, produces the smaller particles, emulsion droplets, consisting of triglycerides, early digestion products, and later on these small particles are broken down into still smaller ones, known as mixed micelles, consequence of bile salts combining with these materials, further digestion is also part of this process, need to get to the stage of mixed micelles that contain the monoglycerides and fatty acids that enables them to get at the surface of the absorbing cell, enterocyte, and then these arrows indicate the components that are absorbed, bile salts are resorbed and recycled, fatty acids of small size, 12 carbons, go through these cells directly, and they are polar enough, water soluble enough that they can get directly into the blood and carried by protein albumin. Have a simple short circuit way of getting through the absorbing cell and on their way. Vast majority of fatty acids are longer, have more carbons than this. Milk has short chain hydrocarbons, special fluid designed to provide nutrition for young mammals, role is to get some nutrition there fast, and other material to show up at later time, spread out the nutrient value. These short chain hydrocarbons, role of fuel into circulation at a rapid rate. Long chain fatty acids get absorbed, undergo further chemistry in enterocyte, go back to triglycerides, still being non polar substances need a lot of help to be carried around. Be big fat globules stuck inside enterocytes. They are packaged into chylomicrons, these chylomicrons are the form that these triglycerides get out of enterocyte and ultimately into blood and lymph. Idea is to start with big insoluble particles and getting down to the stage of absorption.