Copyright © 2000-2003 Mark Brandt, Ph.D. 1Introduction to Lipid MetabolismRoles of LipidsLipids have a wide variety of roles in biological systems. These roles are aconsequence of their chemical and physical properties. Fatty acids and theirderivatives (especially triacylglycerols) can act as highly concentrated energystorage molecules. The high energy density (i.e. the relatively large amount ofenergy released per unit of mass) of fat stores is due to three main factors. 1) Thecompletely reduced carbons of fatty acids have a higher energy content than thepartially oxidized carbons of carbohydrates and proteins. 2) The fortuitous fact thatthe reduced carbons have covalent bonds to light atoms (hydrogen rather than tothe heavier oxygen) means that the fully reduced hydrocarbon compounds arelighter than the partially oxidized carbohydrates. 3) Lipids are hydrophobicmolecules and therefore fat stores contain little water, which would add to theweight of the molecules without adding to the energy content.Because layers of lipids are good insulators, and because adipose tissue haslimited metabolic activity, fat stores can reduce the exchange of heat between anorganism and its environment. This insulation is important for mammals living incold climates, and is especially important for marine mammals, which wouldotherwise rapidly lose their body heat to the surrounding water.As we have already seen, membranes are composed of fatty acid derivatives. Thesecompounds form hydrophobic barriers that separate cells from their surroundingsand which subdivide cells into multiple compartments that allow more finely tunedcontrol of metabolism. Lipids are also used as signaling molecules, such asprostaglandins and steroids, and as enzyme cofactors.Digestion of lipidsThe majority of lipids in a normal diet are present in the form of triacylglycerols.Digestion of these compounds begins in the stomach, which contains acid-stablelipases that release some free fatty acids from dietary triacylglycerols. However, thestomach is not capable of efficiently cleaving triacylglycerols, because thesehydrophobic molecules tend to aggregate, and the lipases are only capable ofhydrolyzing the triacylglycerols at the surface of the aggregates. In addition, thestomach has a small surface area to volume ratio, and therefore many of thetriacylglycerols are not accessible to the enzymes.The small intestine has mechanisms for emulsifying lipids. The process begins bydispersing the lipid aggregates mechanically as a result of the muscles of the smallintestine forcing the partially digested material through the relatively small spacesof the intestinal lumen. In addition, the intestine contains bile acids and bile salts,detergents that break up the lipid aggregates into smaller micelles.Examples of bileacidsCopyright © 2000-2003 Mark Brandt, Ph.D. 2Finally, the small intestine also contains a variety of digestive enzymes produced inthe pancreas. These enzymes include pancreatic cholesteryl ester hydrolase,which releases free cholesterol from cholesteryl esters, pancreatic lipase, whichreleases free fatty acids from the 1- and 3-positions of triacylglycerols, and severalphospholipases, which release free fatty acids from phospholipids. Themonoacylglycerols, partially hydrolyzed phospholipids, and free fatty acids act asadditional detergents and assist in further disrupting the larger lipid aggregates.Absorption of fatty acidsOnce the micelles of free fatty acids, 2-monoacylglycerols, and bile acids becomesmall enough, they can be absorbed from the intestinal lumen into the body. Insidethe body the fatty acids are esterified to re-form triacylglycerols. Thesetriacylglycerols combine with lipoproteins released by the intestines to producechylomicrons, which act as serum transport particles for triacylglycerols.Lipid transportLipid transport is a continuously varying process. During the absorption ofnutrients from the diet, lipids must be transported to the tissues for use. Whenlipids are not being absorbed, they must be transported from adipose stores tomaintain metabolism. Finally, cholesterol redistribution from one tissue to anotherrequires movement of cholesterol through the blood stream.Lipids are hydrophobic and exhibit very limited solubility in aqueous media such asthe blood. Analysis of blood indicates that plasma contains triacylglycerol,phospholipids, cholesterol, and free fatty acids.Free fatty acid levels in the blood are usually quite low (less than 5% of the totalplasma lipids). The levels of free fatty acids depend on the rate of their release byadipose tissue. Most free fatty acids are actually bound to serum albumin. Asodium-dependent active transporter mediates transport of the free fatty acids intocells. Uptake of fatty acids is largely a function of fatty acid concentration inplasma; the relative levels of b-oxidation and esterification to form triacylglycerol orphospholipids depend on the status of the cell.Transport and use of lipids other than free fatty acids requires specializedmechanisms to overcome their insolubility. One option would be to simply formmicelles, and allow these to move freely. However, most lipids are insufficientlysoluble to allow favorable micelle formation. In addition, actual lipid transportrequires a greater degree of control than would result from release of individualCopyright © 2000-2003 Mark Brandt, Ph.D. 3lipid molecules. Actual lipid transport involves specialized particles combining thelipids with specific proteins that allow the control of lipid movement.LipoproteinsLipoproteins consist of a mixture of protein, phospholipid, cholesterol, andtriacylglycerol. The proportions of each vary depending on the specific type ofparticle.Lipid is less dense than protein or water. Initial studies on lipid transport separatedthe different transport forms on the basis of density, with the density differentialbeing largely the result of differing protein content. Lipoproteins are considered tofall into four major classes:1. Chylomicrons (the least dense form)2. VLDL (very low density lipoproteins)3. LDL (low density lipoproteins)4. HDL (high density lipoproteins)In addition, there are