Question

Describe the role lipid digestion, absorption, and transport through the blood relating these topics to the concepts of polarity and solubility in polar solutions such as water and blood.

Answer 1

Role of lipids in the body

Lipids have several roles in the body, these include acting as chemical messengers, storage and provision of energy and so forth.

Chemical messengers

All multicellular organisms use chemical messengers to send information between organelles and to other cells. Since lipids are small molecules insoluble in water, they are excellent candidates for signalling. The signalling molecules further attach to the receptors on the cell surface and bring about a change that leads to an action.

The signalling lipids, in their esterified form can infiltrate membranes and are transported to carry signals to other cells. These may bind to certain proteins as well and are inactive until they reach the site of action and encounter the appropriate receptor.

Storage and provision of energy

Storage lipids are triacylglycerols. These are inert and made up of three fatty acids and a glycerol.

Fatty acids in non esterified form, i.e. as free (unesterified) fatty acids are released from triacylglycerols during fasting to provide a source of energy and to form the structural components for cells.

Dietary fatty acids of short and medium chain size are not esterified but are oxidized rapidly in tissues as a source of ‘fuel”.

Longer chain fatty acids are esterified first to triacylglycerols or structural lipids

The major products of lipid digestion - fatty acids and 2-monoglycerides - enter the enterocyte by simple diffusion across the plasma membrane. A considerable fraction of the fatty acids also enter the enterocyte via a specific fatty acid transporter protein in the membrane.

Absorption of fat:

Lipids are transported from the enterocyte into blood by a mechanism distinctly different from what we've seen for monosaccharides and amino acids.

Once inside the enterocyte, fatty acids and monoglyceride are transported into the endoplasmic reticulum, where they are used to synthesize triglyeride. Beginning in the endoplasmic reticulum and continuing in the Golgi, triglyceride is packaged with cholesterol, lipoproteins and other lipids into particles called chylomicrons. Remember where this is occurring - in the absorptive enterocyte of the small intestine.

Chylomicrons are extruded from the Golgi into exocytotic vesicles, which are transported to the basolateral aspect of the enterocyte. The vesicles fuse with the plasma membrane and undergo exocytosis, dumping the chylomicrons into the space outside the cells.

Because chylomicrons are particles, virtually all steps in this pathway can be visualized using an electron microscope, as the montage of images to the right demonstrates.

Transport of lipids into the circulation is also different from what occurs with sugars and amino acids. Instead of being absorbed directly into capillary blood, chylomicrons are transported first into the lymphatic vessel that penetrates into each villus. Chylomicron-rich lymph then drains into the system lymphatic system, which rapidly flows into blood. Blood-borne chylomicrons are rapidly disassembled and their constitutent lipids utilized throughout the body.

Emulsification, Hydrolysis and Micelle Formation

Bile acids play their first critical role in lipid assimilation by promoting emulsification. As derivatives of cholesterol, bile acids have both hydrophilic and hydrophobic domains (i.e. they are amphipathic). On exposure to a large aggregate of triglyceride, the hydrophobic portions of bile acids intercalate into the lipid, with the hydrophilic domains remaining at the surface. Such coating with bile acids aids in breakdown of large aggregates or droplets into smaller and smaller droplets.
Hydrolysis of triglyceride into monoglyceride and free fatty acids is accomplished predominantly by pancreatic lipase. The activity of this enzyme is to clip the fatty acids at positions 1 and 3 of the triglyceride, leaving two free fatty acids and a 2-monoglyceride. The drug orlistat (Xenical) that is promoted for treatment of obesity works by inhibiting pancreatic lipase, thereby reducing the digestion and absorption of fat in the small intestine. Lipase is a water-soluble enzyme, and with a little imagination, it's easy to understand why emulsification is a necessary prelude to its efficient activity. Shortly after a meal, lipase is present within the small intestine in rather huge quantities, but can act only on the surface of triglyeride droplets. For a given volume of lipid, the smaller the droplet size, the greater the surface area, which means more lipase molecules can get to work.
As monoglycerides and fatty acids are liberated through the action of lipase, they retain their association with bile acids and complex with other lipids to form structures called micelles. Micelles are essentially small aggregates (4-8 nm in diameter) of mixed lipids and bile acids suspended within the ingesta. As the ingesta is mixed, micelles bump into the brush border of small intestinal enterocytes, and the lipids, including monoglyceride and fatty acids, are taken up into the epithelial cells