Lipoprotein Metabolism

Three key pathways in lipoprotein metabolism.
 Exogenous pathway, in which chylomicrons clear dietary lipids.

 Endogenous pathway, in which VLDL and LDL transport and distribute endogenously
synthesized lipids (those synthesized in the body).
 Reverse cholesterol transport, in which HDL clears excess cholesterol.
Digestion and Absorption of Lipids
Two key enzymes involved in lipoprotein metabolism, which both degrade triacylglycerol to
glycerol and free fatty acids.
 Lipoprotein lipase, which is bound to the endothelial layer of peripheral capillaries.
 Hepatic lipase, which is also a phospholipase (meaning it can degrade phospholipids) and
which localizes within hepatic endothelial cells.
1. The first step in the digestion of triglycerides and phospholipids begins in the mouth as
lipids encounter saliva. Next, the physical action of chewing coupled with the action of
emulsifiers enables the digestive enzymes to do their tasks. The enzyme lingual lipase,
along with a small amount of phospholipid as an emulsifier, initiates the process of
digestion. These actions cause the fats to become more accessible to the digestive
enzymes. As a result, the fats become tiny droplets and separate from the watery
components.
2. In the stomach, gastric lipase starts to break down triglycerides into diglycerides and
fatty acids. Within two to four hours after eating a meal, roughly 30 percent of the
triglycerides are converted to diglycerides and fatty acids. The stomach’s churning and
contractions help to disperse the fat molecules, while the diglycerides derived in this
process act as further emulsifiers. However, even amid all of this activity, very little fat
digestion occurs in the stomach.
3. As stomach contents enter the small intestine, it combine the fats with its own watery
fluids. Bile which contains bile salts, lecithin, acts as an emulsifier.
4. Once the stomach contents have been emulsified, fat-breaking enzymes work on the
triglycerides and diglycerides to sever/ cut or slice the fatty acids from their glycerol
foundations.
5. As pancreatic lipase enters the small intestine, it breaks down the fats into free fatty
acids and monoglycerides.
6. Bile salts envelop the fatty acids and monoglycerides to form micelles. Micelles have a
fatty acid core with a water-soluble exterior. This allows efficient transportation to the
intestinal microvillus. Here, the fat components are released and disseminated into the
cells of the digestive tract lining.
Endogenous pathway
1. When the VLDL particles are released into the bloodstream, they encounter high-density
lipoprotein (HDL) particles that donate apolipoprotein C-II and apolipoprotein E to the
VLDL particles.
2. The VLDL then circulates in the bloodstream and travel to the peripheral adipose and
muscle tissues in the body. By way of a hydrolysis reaction, the triglycerides can be
broken down to supply fatty acids and glycerol to the cells as a source of energy.
3. The energy-depleted VLDL remnants, also known as intermediate density lipoproteins
(IDLs), have a higher proportion of cholesterol, as the triglycerides have been
consumed. They continue to circulate in the bloodstream until they are absorbed by the
liver with the involvement of apolipoproetein E. Alternatively, the remnants can be further
hydrolyzed by hepatic lipase, releasing more glycerol and fatty acids, to form low-density
lipoproteins (LDL) that are the type of lipoproteins that are richest in cholesterol.
4. The LDL circulates in the bloodstream and can be absorbed by cells in the liver or
peripheral tissues. The particles can bind to the target tissue with the LDL receptor with
the involvement of apolipoprotein B-100. The LDL can then be absorbed by endocytosis,
and the particles hydrolyzed to release lipids such as cholesterol.
Endocytosis= the ingestion of large particles (such as bacteria) and the uptake of fluids or
macromolecules in small vesicles ( Ex. Phagocytosis)
Exogenous pathway
1. Triglycerides from the diet are digested in the gastrointestinal tract to form
monoglycerides and free fatty acids through various processes, including gastric lipase,
bile emulsification and pancreatic lipase. Similarly, cholesterol esters from the diet
undergo a process of de-esterification to form free cholesterol.
2. Monoglycerides, free fatty acids and cholesterol are soluble in the bile acid micelles and
can be absorbed from the chymus into the enterocytes due to their smaller size.
3. Inside the enterocytes, they are reassembled into triglycerides and combined with
cholesterol to form large chylomicron lipoproteins. Apolipoprotein B-48 regulates the
secretion of these particles into the lacteals, and the chylomicrons then circulate through
the lymphatic vessels and into the bloodstream.
4. Chylomicrons are responsible for the transport of dietary triglycerides and cholesterol
from the enterocytes and into the circulation system. In the adipose and muscle tissue
the majority of the triglycerides in the chylomicron can be converted to fatty acids and
glycerol to provide a source of energy. Depleted of energy, the chylomicron remnants
rich in cholesterol travel back to the liver to be cleared from the body, through a process
mediated by apoprotein E.
Reverse cholesterol transport

= is involved in the process of removal of excess cholesterol from the plaque with
subsequent transport of this cholesterol to the liver for degradation to bile acids.
1. free cholesterol is removed from peripheral cells by interaction between

serum lipoproteins and cells.
2. Free cholesterol released from the cell is esterified by lecithin:
cholesterol acyltransferase and incorporated into the HDL particle
HDL cholesteryl esters can be transferred to apolipoprotein B (apoB)-containing
lipoproteins in exchange for triacylglycerols by cholesteryl ester transfer protein .
3. Finally, cholesteryl esters from lipoproteins are removed from plasma by the liver
for degradation to bile acids.

Lipoprotein Metabolism

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Lipoprotein Metabolism

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Three key pathways in lipoprotein metabolism.

 Exogenous pathway, in which chylomicrons clear dietary lipids.

Digestion and Absorption of Lipids

Reverse cholesterol transport

1. free cholesterol is removed from peripheral cells by interaction between

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