ECDA

September 2009

LIPID DIGESTION Lipids in the diet are most commonly

triglycerides or neutral fats found in both animals and plants. Cholesterols and phospholipids also are normal fats in foods.

Because a large quantity of fat dumped into the blood stream at one time is deleterious to health and might fatally clog the circulatory system, a mechanism for retardation of stomach emptying of fat is present.

LIPID DIGESTION When a bit of fat enters the duodenum, a

chemical message is sent to the brain which then signals the stomach to cease releasing more material into the duodenum until it has taken care of the fat.

Only a small amount of fat is digested in the stomach by gastric lipase, a fat-splitting enzyme.

Essentially, most fat digestion occurs in the small intestine.

Digestion, Mobilization, and Transport

FATTY ACID METABOLISM

First, the fat globules must be broken into small sizes so enzymes can act. This emulsification is accomplished under the influence of bile, a secretion of the liver.

Bile is stored in the gallbladder and drawn upon as needed. Bile contains a large amount of bile salts, the main function of which is to make fat globules break down.

The "detergent" function of bile salts is essential to fat digestion, for the lipase (fat-splitting enzymes) can "attack" the fat globules only on their surfaces. The smaller the fat particles, the better digestion.

LIPID DIGESTION Pancreatic lipase is the most important enzyme

in fat digestion. In concert, the epithelial lining of the small intestine also releases a small amount of lipase.

Both lipases (pancreatic and intestinal) act to digest fat. Fats in the diet are broken down into free fatty acids

and monoglycerides by pancreatic lipase, which forms a 1:1 complex with a protein called colipase which is necessary for its activity.

The activated complex can only work at a water-fat interface: it is therefore essential that fatty acids (FA) be emulsified by bile salts for optimal activity of these enzymes.

LIPID DIGESTION Bile salts also form micelles, small sphericle globules.

These micelles help remove the end products of fat digestion so further fat digestion can continue.

These little micelles transport their cargo to the lining of the small intestine, where they're absorbed.

LIPID DIGESTION Upon contacting the membrane lining of

the small intestine, the end products of fat digestion become dissolved in the membrane and diffuse to the interior of the cell. As the split fat molecules enter the lining cells, intestinal lipase (enzyme) helps to further digest them.

Small amounts of fatty acids are absorbed directly into the blood going to the liver.

LIPID DIGESTION

Dietary fat is non-polar and must be carried in the circulation as lipoproteins, a relatively polar substance.

The protein molecules provide a polar coat for the non-polar lipid and thus enable transportation in the polar bloodstream.

LIPOPROTEIN

LIPID DIGESTION In general lipoprotein

particles range in size from 10 to 1000 nm.

They are composed of a hydrophobic core containing cholesteryl esters, triglycerides, fatty acids and fat-soluble vitamins.

The surrounding hydrophilic layer is composed of various apolipoproteins, phospholipids and cholesterol.

ChylomicronsLIPID DIGESTION

Chylomicrons are the largest (1000 nm) and least dense (<0.95) of the lipoproteins. They contain only 1-2% protein, 85-88% triglycerides, ~8% phospholipids, ~3% cholesteryl esters and ~1% cholesterol.

Chylomicrons contain several types of apolipoproteins including apo-AI,II & IV, apo-B48, apo-CI, II & III, apo-E and apo-H.

ChylomicronsLIPID DIGESTION

Chylomicrons are produced for the purpose of transporting dietary triglycerides and cholesterol absorbed by intestinal epithelia.

Chylomicron assembly originates in the intestinal mucosa. Excretion into the plasma is facilitated through the lymphatic system.

Once transported to tissues, triglycerides contained in chylomicrons are hydrolyzed while the chylomicron remnant, including residual cholesterol, is taken up by the liver.

VLDLLIPID DIGESTION

Very low density lipoproteins (VLDL) are the next step down from chylomicrons in terms of size and lipid content.

They are approximately 25-90 nm in size (MW 6-27 million), with a density of ~0.98. They contain 5-12% protein, 50-55% triglycerides, 18-20% phospholipids, 12-15% cholesteryl esters and 8-10% cholesterol.

VLDLLIPID DIGESTION

VLDL assembly in the liver involves the early association of lipids with apo-B100 mediated by microsomal triglyceride transfer protein while apo-B100 is translocated to the lumen of the ER.

Lipoprotein lipase also removes triglycerides from VLDL in the same way as from chylomicrons.

IDLLIPID DIGESTION

Intermediate density lipoproteins are smaller than VLDL (40 nm) and more dense (~1.0). They contain the same apolipoproteins as VLDL. They are composed of 10-12% protein, 24-30% triglycerides, 25-27% phospholipids, 32-35% cholesteryl esters and 8-10% cholesterol.

IDLs are derived from triglyceride depletion of VLDL. IDLs can be taken up by the liver for reprocessing, or upon further triglyceride depletion, become LDL.

LDLLIPID DIGESTION

Low density lipoproteins are smaller than IDL (≈20 nm) (MW approximately 3.5 million) and more dense (~1.04). They contain the apolipoprotein apo-B100. LDL contains 20-22% protein, 10-15% triglycerides, 20-28% phospholipids, 37-48% cholesteryl esters and 8-10% cholesterol.

LDL is the main transporter of cholesterol and cholesteryl esters and makes up more than half of the total lipoprotein in plasma. LDL is absorbed by the liver and other tissues via receptor mediated endocytosis.

LDLLIPID DIGESTION

HDLLIPID DIGESTION

High density lipoproteins are the smallest of the lipoproteins (6-12.5 nm) (MW 175-500KD) and most dense (~1.12). HDL contains approximately 55% protein, 3-15% triglycerides, 26-46% phospholipids, 15-30% cholesteryl esters and 2-10% cholesterol.

The HDL protein particle accumulates cholesteryl esters by the esterification of cholesterol by lecithin-cholesterol acyl-transferase (LCAT).

HDLLIPID DIGESTION

HDL can acquire cholesterol from cell membranes and can transfer cholesteryl esters to VLDL and LDL via transferase activity in apo-D.

HDL can return to the liver where cholesterol is removed by reverse cholesterol transport, thus serving as a scavenger to free cholesterol. The liver can then excrete excess cholesterol in the form of bile acids.

LIPID DIGESTION

LIPID DIGESTION Contrary to popular understanding, when

we speak of "good and bad" blood cholesterol levels, we are not speaking of different types of cholesterol molecules.Due to their poor solubility in the blood

stream, cholesterol, triglycerides and other lipids require transport vehicles such as lipoprotein particles.

It is these transport vehicles (lipoproteins) that determine the "good and bad" nature of cholesterol.

LIPID DIGESTION Medically, the "good and bad" terminology

normally refers to HDL and LDL, respectively.

Lipoproteins differ in their content of proteins and lipids. The higher the ratio of protein to lipid content

the higher the density. In general, the higher the density of a

lipoprotein particle the smaller it's size and molecular weight.

LIPID DIGESTION

LIPID DIGESTION Low HDL (<35 mg/dL) in the blood

may be associated with increased risk of coronary atherosclerosis, conversely high levels of HDL (>55 mg/dL) appear to have a protective affect.

High LDL levels have been shown to correlate with coronary atherosclerosis.

LIPID DIGESTION

LIPID DIGESTION

The dietary lipids or fatty acids brought to the liver via lipoprotein carriers are either metabolized to produce energy or are stored in adipose cells as triglyceride reserves.Insulin promotes the formation of triglycerides

from dietary monoglycerides.Glucagon and adrenaline promotes catabolism

of triglycerides into fatty acids for beta-oxidation process.