VLDLs and chylomicrons shrink as they lose triglyceride and become 'remnants'. These become bound to receptors on hepatocytes and engulfed by phagocytosis.

Remnants of VLDLs and Chylomicrons

The illustration at the left is a section of the main diagram. The curved line represents the liver -- or an hepatocyte -- and the blue abbreviations are transporters embedded in its membrane. Both remnants will be taken into the hepatocyte by endocytosis as indicated by the dashed arrows.

The Space of Disse

The illustration at the right shows a large, porous capillary in the liver. The small particles are remnants. The line at the left in the illustration represents the hepatocyte membrane. The small circle at the top left represents a chylomicron remnant (CMR) and the one just below it is the remnant of VLDL called intermediate density lipoprotein (LDL). Notice the apoB48 and B100 apoproteins on the appropriate remnant. Also notice that the core of each contains approximately equal amounts of cholesterol ester (orange) and triglyceride (lavender).

Lipoprotein remnants are removed from circulation by the liver in three stages: entrance, sequestration and uptake.

Entrance

The capillaries in the liver are much larger in diameter than typical capillaries. Such vessels are called sinusoids. Additionally, there is a significant amount of space surrounding the sinusoids called the space of Disse. Small lipoproteins can enter and leave through the numerous openings (fenestrae) in the sinusoids.

Sequestration

The hepatocyte cell membrane has numerous large, branched molecules called haparan sulfate proteoglycans (HSPGs) (not shown) that extend into the space of Disse. These serve as attachment sites for many different particles. When the lipoprotein remnants contact them they become bound and sequester (confined) against the hepatic cell membrane.

Uptake

There are two types of receptors located in the hepatocyte membrane.

• Lipoprotein-receptor related protein (LRP) requires apoE to facilitates the binding of the sequestered remnants to this receptor. This is illustrated by 'apoE' found between 'LRP' and each type of remnant. ApoE is secreted into the space of Disse by the hepatocyte. Also, apoE might still be on the remnants if not lost when shedding excess coat material.
• The low density lipoprotein receptor (LDL-R) does not require apoE; it interacts with the B100 on IDLs as suggested in the illustration.

Upon attaching to the receptors the entire assembly is engulfed and taken into (endocytosis) the hepatocyte. Internally the lipoproteins are disassembled and the receptors are recycled back to the cell surface.

Continue to High Density Lipoproteins

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