Fatty Acids: Building Blocks, Fuel and Signaling Molecules W. M. Grogan, Ph.D. OBJECTIVES 1. Draw the structures and give the names of commonly occurring saturated and unsaturated fatty acids. 2. Draw the structures for unsaturated fatty acids, given the systematic or shorthand nomenclature. 3. Give shorthand nomenclature, given structures of unsaturated fatty acids. 4. Describe the chemical and physical properties of fatty acids. 5. Discuss the physiological and nutritional significance of fatty acids. RESOURCES Lehninger, Chap. 10 I. OVERVIEW What are lipids and why are they important? A. Operational definition Organic biomolecules which are soluble in organic, apolar solvents and, as a rule, insoluble or sparingly soluble in water. B. II. Importance 1. detergents, plastics, paint, lubricants 2. nutrition 3. metabolic energy (60­80%) 4. membrane and lipoprotein structure and function 5. cell recognition and interaction with environment 6. biologically active molecules 7. polysaccharide carriers 8. covalent modification 9. derangements of lipid metabolism FATTY ACIDS The basic building blocks of most lipids [R­CO2H R­CO2 ­ + H + ]
A. Saturated fatty acids: Structures and nomenclature [R = CH3­(CH2­)x] 1. short chain fatty acids (C2 ­ C6) 2. medium chain fatty acids (C8 ­ C12) 3. long chain fatty acids (C14 ­ C24+) Commonly Occurring Saturated Fatty Acids CH3­CO2H acetic acid CH3­CH2­CO2H propionic (propanoic) acid CH3­CH2­CH2­CO2H butyric (butanoic) acid CH3­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CO2H lauric (dodecanoic) acid CH3­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­ CH2­CO2H palmitic (hexadecanoic) acid CH3­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­ CH2­CH2­CO2H stearic (octadecanoic) acid stearic acid (short­hand structure) Application: High intake of saturated fatty acids in the form of saturated fat is associated with increased risk of atherosclerosis and coronary heart disease. Question: Are all saturated fatty acids nutritionally and metabolically equivalent? B. Unsaturated fatty acids
Figure 1: Structures and nomenclature for commonly occurring unsaturated fatty acids. C. Short­hand nomenclatures 1. Δ (Greek character, "delta") ­ double bond positioned from the carboxyl end 2. ω (Greek character, "omega") ­ double bond positioned from the methyl end (variant: “n­” instead of “ω”) D. Families of fatty acids (ω3, ω6, ω7, ω9; also, n­3, n­6, n­7, n­9)
1. metabolic significance: Fatty acids of the same family are derived from the same precursor and share the same biosynthetic pathway. 2. Essential fatty acids: Linoleic and linolenic acids are precursors for all ω6 and ω3 fatty acids, respectively; components of cell membranes; necessary for normal growth and function. 3. Biological activity: Prostaglandins, thromboxanes, leukotrienes are synthesized from 20­carbon ω6 and ω3 (eicosenoic) fatty acids. Metabolites from different families have different physical properties and biological activities. Applications: Substitution of saturated by unsaturated fatty acids in the diet significantly lowers the serum cholesterol level. However, ω6 fatty acids may lower HDL as well as LDL cholesterol. Certain ω3 fatty acids are reported to lower serum triglycerides while raising HDL. The ω3/ω6/ω9 balance may influence many biological processes, including neurological development, the progress of atherosclerosis and inflammation. Open­ended Question: What are the nutritional and metabolic effects of unsaturated fats? Figure 2: Cis and trans double bonds as they occur in unsaturated fatty acids. Trans fatty acids are similar to saturated in physical properties and biological activity. E. Trans fatty acids: Trans unsaturation is most likely to be found in animal fats or fats and oils that have been industrially processed.
1. Anaerobic microorganisms found in the digestive tracts of ruminant animals synthesize trans unsaturated fatty acids, which are incorporated into animal and milk fats (butter and cheese). 2. Unlike a single carbon­carbon bond, a substantial energy barrier opposes rotation around a double bond. This barrier can be overcome when unsaturated fatty acids are exposed to heat or catalysts involved in industrial processing of fats and oils. When rotation occurs, the trans conformation is thermodynamically favored, resulting in conversion of most cis unsaturated fatty acids to trans. The position of double bonds may also shift under these conditions. 3. High intakes of fats or oils high in trans unsaturated fatty acids are associated with increased LDL, decreased HDL and increased risk of atherosclerosis/heart disease. 4. Cis­trans and positional isomerization alter the biological activities of unsaturated fatty acids. F. Physical properties of fatty acids 1. Melting point increases with increasing chain length; decreases with increasing cis unsaturation (Double bond disrupts molecular packing). (See Lehninger, Fig. 10­1) The effect of of trans unsaturation on melting point is much less pronounced. 2. Boiling point follows same trends. 3. Water solubility decreases with increasing chain length; ionized fatty acids form aggregate structures (micelles and multilamellar forms) which disperse in water. Figure 3: Structures of soaps and other amphiphilic lipids.
Observation: Above a certain very low concentration (the critical micellar concentration) fatty acids form multilamellar vesicles at pH 7, and micelles at pH 9. Open­Ended Question: What determines the physical structure formed by a particular amphiphilic lipid? G. Chemical reactions Figure 4 Figure 5: Hydrolysis or saponification of a fatty acid triester. Figure 6: Catalytic hydrogenation of an unsaturated fatty acid, as used in industrial processing of dietary fats and oils. Hydrogenation may be complete or partial. A high proportion of remaining double bonds may be isomerized to trans.
Figure 7: Autooxidation of lipids occurs in foods and in biological tissues, where it is implicated in the etiology and pathogenesis of many diseases, including aging, atherosclerosis, diabetes and cancer. In foods, it is controlled by natural or synthetic antioxidants, exclusion of oxygen and/or hydrogenation of unsaturated lipids. In the cell, it is controlled by natural antioxidants and by enzyme catalyzed reactions that will be covered elsewhere. H. Nomenclature for modified carboxyl group 1. Protonated acid ­ stearic 2. Ionized acid ­ stearate 3. Derivatized fatty acid ­ X­stearate CH3­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­CH2­ CH2­CH2­CO2CH3 Example: methyl palmitate 4. Another compound derivatized with fatty acid ­ stearoyl­X Figure 8: As a derivative of glycerol, the usual nomenclature for this compound is 1­ oleoylglycerol. It could also be named as a derivative of the fatty acid; i.e., glyceryl­1­oleate.