Digestion and transport
Fatty acids are usually ingested as triglycerides, which cannot be absorbed by the intestine. They 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. People who have had their gallbladder removed due to gall stones consequently have great difficulty digesting fats. Most are absorbed as free fatty acids and 2-monoglycerides, but a small fraction is absorbed as free glycerol and as diglycerides. Once across the intestinal barrier, they are reformed into triglycerides and packaged into chylomicrons or liposomes, which are released into the lacteals, the capillaries of the lymph system and then into the blood. Eventually, they bind to the membranes of hepatocytes, adipocytes or muscle fibers, where they are either stored or oxidized for energy. The liver acts as a major organ for fatty acid treatment, processing chylomicron remnants and liposomes into the various lipoprotein forms, namely VLDL and LDL. Fatty acids synthesized by the liver are converted to triglyceride and transported to the blood as VLDL. In peripheral tissues, lipoprotein lipase digests part of the VLDL into LDL and free fatty acids, which are taken up for metabolism. This is done by the removal of the triglycerides contained in the VLDL. What is left of the VLDL absorbs cholesterol from other circulating lipoproteins, becoming LDLs. LDL is absorbed via LDL receptors. This provides a mechanism for absorption of LDL into the cell, and for its conversion into free fatty acids, cholesterol, and other components of LDL. The liver controls the concentration of cholesterol in the blood by removing LDL. Another type of lipoprotein known as high density lipoprotein, or HDL collects cholesterol, glycerol and fatty acids from the blood and transports them to the liver. In summary:
* Chylomicrons carry diet-derived lipids to body cells
* VLDL's carry lipids synthesized by the liver to body cells
* LDL's carry cholesterol around the body
* HDL's carry cholesterol from the body back to the liver for breakdown and excretion.
When blood sugar is low, glucagon signals the adipocytes to activate hormone sensitive lipase, and to convert triglycerides into free fatty acids. These have very low solubility in the blood, typically about 1 μM. However, the most abundant protein in blood, serum albumin, binds free fatty acids, increasing their effective solubility to ~ 1 mM. Thus, serum albumin transports fatty acids to organs such as muscle and liver for oxidation when blood sugar is low.