Introduction to Lipid Metabolism Roles of Lipids Lipids have a wide variety of roles in biological systems These roles are a consequence of their chemical and physical properties Fatty acids and their derivatives especially triacylglycerols can act as highly concentrated energy storage molecules The high energy density i e the relatively large amount of energy released per unit of mass of fat stores is due to three main factors 1 The completely reduced carbons of fatty acids have a higher energy content than the partially oxidized carbons of carbohydrates and proteins 2 The fortuitous fact that the reduced carbons have covalent bonds to light atoms hydrogen rather than to the heavier oxygen means that the fully reduced hydrocarbon compounds are lighter than the partially oxidized carbohydrates 3 Lipids are hydrophobic molecules and therefore fat stores contain little water which would add to the weight of the molecules without adding to the energy content Because layers of lipids are good insulators and because adipose tissue has limited metabolic activity fat stores can reduce the exchange of heat between an organism and its environment This insulation is important for mammals living in cold climates and is especially important for marine mammals which would otherwise rapidly lose their body heat to the surrounding water As we have already seen membranes are composed of fatty acid derivatives These compounds form hydrophobic barriers that separate cells from their surroundings and which subdivide cells into multiple compartments that allow more finely tuned control of metabolism Lipids are also used as signaling molecules such as prostaglandins and steroids and as enzyme cofactors Digestion of lipids The 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 stable lipases that release some free fatty acids from dietary triacylglycerols However the stomach is not capable of efficiently cleaving triacylglycerols because these hydrophobic molecules tend to aggregate and the lipases are only capable of hydrolyzing the triacylglycerols at the surface of the aggregates In addition the stomach has a small surface area to volume ratio and therefore many of the triacylglycerols are not accessible to the enzymes The small intestine has mechanisms for emulsifying lipids The process begins by dispersing the lipid aggregates mechanically as a result of the muscles of the small intestine forcing the partially digested material through the relatively small spaces of 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 bile acids Copyright 2000 2003 Mark Brandt Ph D 1 Finally the small intestine also contains a variety of digestive enzymes produced in the pancreas These enzymes include pancreatic cholesteryl ester hydrolase which releases free cholesterol from cholesteryl esters pancreatic lipase which releases free fatty acids from the 1 and 3 positions of triacylglycerols and several phospholipases which release free fatty acids from phospholipids The monoacylglycerols partially hydrolyzed phospholipids and free fatty acids act as additional detergents and assist in further disrupting the larger lipid aggregates Absorption of fatty acids Once the micelles of free fatty acids 2 monoacylglycerols and bile acids become small enough they can be absorbed from the intestinal lumen into the body Inside the body the fatty acids are esterified to re form triacylglycerols These triacylglycerols combine with lipoproteins released by the intestines to produce chylomicrons which act as serum transport particles for triacylglycerols Lipid transport Lipid transport is a continuously varying process During the absorption of nutrients from the diet lipids must be transported to the tissues for use When lipids are not being absorbed they must be transported from adipose stores to maintain metabolism Finally cholesterol redistribution from one tissue to another requires movement of cholesterol through the blood stream Lipids are hydrophobic and exhibit very limited solubility in aqueous media such as the 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 total plasma lipids The levels of free fatty acids depend on the rate of their release by adipose tissue Most free fatty acids are actually bound to serum albumin A sodium dependent active transporter mediates transport of the free fatty acids into cells Uptake of fatty acids is largely a function of fatty acid concentration in plasma the relative levels of b oxidation and esterification to form triacylglycerol or phospholipids depend on the status of the cell Transport and use of lipids other than free fatty acids requires specialized mechanisms to overcome their insolubility One option would be to simply form micelles and allow these to move freely However most lipids are insufficiently soluble to allow favorable micelle formation In addition actual lipid transport requires a greater degree of control than would result from release of individual Copyright 2000 2003 Mark Brandt Ph D 2 lipid molecules Actual lipid transport involves specialized particles combining the lipids with specific proteins that allow the control of lipid movement Lipoproteins Lipoproteins consist of a mixture of protein phospholipid cholesterol and triacylglycerol The proportions of each vary depending on the specific type of particle Lipid is less dense than protein or water Initial studies on lipid transport separated the different transport forms on the basis of density with the density differential being largely the result of differing protein content Lipoproteins are considered to fall 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 two minor classes IDL intermediate density lipoproteins which are intermediate between VLDL and LDL and chylomicron remnants which are the residual protein and lipid after the completion of triacylglycerol extraction from chylomicrons The proteins present in lipoproteins are called apolipoproteins or simply apoproteins The prefix apo means without with apolipoprotein referring