Saponifiable and Nonsaponifiable Lipids

Transcription

1 Sign In Forgot Password Register username username password password Sign In If you like us, please share us on social media. The latest UCD Hyperlibrary newsletter is now complete, check it out. ChemWiki BioWiki GeoWiki StatWiki PhysWiki MathWiki SolarWiki BioWiki: The Dynamic Biology E-textbook > Biochemistry > Lipids > Lipid Structure Lipid Structure Lipids can be considered to be biological molecules which are soluble in organic solvents, such as chloroform/methanol, and are sparingly soluble in aqueous solutions. Saponifiable and Nonsaponifiable Lipids Properties of Lipids Fatty Acid Structure and Conformation Nomenclature of Fatty Acids Glycerophospholipid and Sphingolipids Triacylglyceride/Phospholipid Stereochemistry Lipids in Archaea, Prokaryotes and Eukaryotes References Contributors Saponifiable and Nonsaponifiable Lipids There are two major classes, saponifiable and nonsaponifiable, based on their reactivity with strong bases. The nonsaponifiable classes include the "fat-soluble" vitamins (A, E) and cholesterol. 1/11

2 Figure: Examples saponifiable and nonsaponifiable lipids Saponification is the process that produces soaps from the reaction of lipids and a strong base. The saponifiable lipids contain long chain carboxylic s, or fatty s, esterified to a backbone molecule, which is either glycerol or sphingosine. Note on nomenclature: Lipids are often distinguished from another commonly used word, fats. Some define fats as lipids that contain fatty that are esterified to glycerol. The terms are used synonymously here. The major saponifiable lipids are triacylglycerides, glycerophospholipids, and the sphingolipids. The first two use glycerol as the backbone. Triacylglycerides have three fatty s esterified to the three OHs on glycerol. Glycerophospholipids have two fatty s esterified at carbons 1 and 2, and a phospho-x group esterifed at C3. Sphingosine, the backbone for sphingolipids, has a long alkyl group connected at C1 and a free amine at C2, as a backbone. In sphingolipids, a fatty is attached through an amide link at C2, and a H or esterified phospho-x group is found at C3. A general diagram showing the difference in these structures is shown below. Figure: Classification of common phospholipids, glycolipids, and triacylglyerides The actual chemical structures of these lipids are shown below. Figure: Structures of common phospholipids 2/11

3 Figure: Comparison of lipids with glycerol and sphingosine as backbones Properties of Lipids The structure of these molecules determines their function. For example, the very insoluble triacylglycerides are used as the predominant storage form of chemical energy in the body. In contrast to polysaccharides such as glycogen (a polymer of glucose), the Cs in the acyl-chains of the triacylglyceride are in a highly reduced state. The main source of energy to drive not only our bodies but also our society is obtained through 3/11

4 oxidizing carbon-based molecules to carbon dioxide and water, in a reaction which is highly exergonic and exothermic. Sugars are already partway down the free energy spectrum since each carbon is partially oxidized. 9 kcal/mol can be derived from the complete oxidation of fats, in contrast to 4.5 kcal/mol from that of proteins or carbohydrates. In addition, glycogen is highly hydrated. For every 1 g of glycogen, 2 grams of water is H- bonded to it. Hence it would take 3 times more weight to store the equivalent amount of energy in carbohydrates as is stored in triacylglyceride, which are stored in anhydrous lipid "drops" within cells. The rest of this unit on lipids will focus not on triacylglycerides, whose main function is energy storage, but on fatty s and phospholipids, and the structures they form in aqueous solution. The structure of fatty s and phospholipids show them to amphiphilic - i.e. they have both hydrophobic and hydrophilic domains. Fatty s can be represented in "cartoon-form" as single chain amphiphiles with a circular polar head group and a single acyl non-polar tail extending from the head. Likewise, phospholipids can be shown as double chain amphiphiles. Even cholesterol can be represented this way, with its single OH group as the polar head, and the rigid 4 member rings as the hydrophobic tail. Even through there are a very large number of fatty s which can be esterified to C1 and C2 of phospholipids and a variety of P-X groups at C3, making the phospholipids and fatty s extremely heterogeneous groups of molecules, their role in biological structures can be understood quite simply by modeling them either as single or double chain amphiphiles. This reduces their apparent complexity dramatically. In addition, they, in contrast to carbohydrates, amino s, and nucleotides, do not form covalent polymers. Hence we will start our studies of biological molecules with lipids (fatty s and phospholipids) and then apply our understanding of this class of molecules to the more complex systems of biological polymers. We will see that phospholipids and sphingolipids are essential components of membrane structure. Cholesterol is also found in membranes and is a precursor of steroid hormones. Fatty Acid Structure and Conformation Fatty s can be saturated (contain no double bonds in the acyl chain), or unsaturated (with either one - monounsaturated - or multiple - polyunsaturated - double bond(s)). The table below gives the names, in a variety of formats, of common fatty s. Table: Names and structures of the most common fatty s COMMON BIOLOGICAL SATURATED FATTY ACIDS Symbol Common name Systematic Name Structure mp(c) 12:0 Lauric Dodecanoic CH 3 (CH 2 ) 10 COOH :0 Myristic 16:0 Palmitic 18:0 Stearic Tetradecanoic Hexadecanoic Octadecanoic CH 3 (CH 2 ) 12 COOH 52 CH 3 (CH 2 ) 14 COOH 63.1 CH 3 (CH 2 ) 16 COOH :0 Arachidic aicd Eicosanoic CH 3 (CH 2 ) 18 COOH 75.4 Symbol COMMON BIOLOGICAL UNSATURATED FATTY ACIDS Common Name Systematic Name Structure mp(c) 16:1 D9 Palmitoleic 18:1 D9 Oleic 18:2 D9,12 Linoleic 18:3 D9,12,15 a-linolenic 20:4 D5,8,11,14 Arachidonic 20:5 D5,8,11,14,17 EPA Hexadecenoic 9-Octadecenoic 9,12 - Octadecadienoic 9,12,15 - Octadecatrienoic 5,8,11,14- Eicosatetraenoic CH 3 (CH 2 ) 5 CH=CH-(CH 2 ) 7 COOH -0.5 CH 3 (CH 2 ) 7 CH=CH-(CH 2 ) 7 COOH 13.4 CH 3 (CH 2 ) 4 (CH=CHCH 2 ) 2 (CH 2 ) 6 COOH -9 CH 3 CH 2 (CH=CHCH 2 ) 3 (CH 2 ) 6 COOH -17 CH 3 (CH 2 ) 4 (CH=CHCH 2 ) 4 (CH 2 ) 2 COOH -49 CH 3 CH 2 (CH=CHCH 2 ) 5 (CH 2 ) 2 COOH :6 D4,7,10,13,16,19 DHA Docosohexaenoic % FATTY ACIDS IN VARIOUS FATS 22:6w3 FAT <16:0 16:1 18:0 18:1 18:2 18:3 20:0 22:1 22:2. 5,8,11,14,17- Eicosapentaenoic Coconut Canola Olive /11

5 Oil Butterfat The figure below shows the relative conformations of saturated and unsaturated fatty s, and in comparison, the conformations and potential energy graph for n-butane, which should provide insight into conformational changes in the nonpolar tail of fatty s arising from rotation around C-C single bonds. We will explore this diagram a bit latter. Figure: Conformations of fatty s and n-butane Conformations of fatty s Jmol: conformations of ethane conformations of propane butane: the gauche conformation Nomenclature of Fatty Acids Symbolic name: given as x:y (Da,b,c) where x is the number of C s in the chain, y is the number of double bonds, and a, b, and c are the positions of the start of the double bonds counting from C1 - the carboxyl C. Saturated fatty s contain no C-C double bonds. Monounsaturated fatty s contain 1 C=C while polyunsaturated fatty s contain more than 1 C=C. Double bonds are usual cis. Systematic name using IUPAC nomenclature: The systematic name gives the number of Cs (e.g. hexadecanoic for 16:0). If the fatty is unsaturated, the base name reflects the number of double bonds (e.g. octadecenoic for 18:1 D9 and octadecatrienoic for 18:3 D9,12,15 ). Common name: (e.g. oleic, which is found in high concentration in olive oil) You should know the common name, systematic name, and symbolic representations for these saturated fatty s: lauric, dodecanoic, 12:0 palmitic, hexadecanoic, 16:0 stearic, octadecanic, 18:0. Learn the following unsaturated fatty s: oleic, octadecenoic, 18:1 D9 linoleic, octadecadienoic, 18:2 D9,12 a-linolenic, octadecatrienoic, 18:3 D9,12,15 (n-3) arachidonic, eicosatetraenoic, 20:4 D5,8,11,14 (n-6) eicosapentenoic (EPA), 20:5 D5,8,11,14,17 (n-3) Note: sometimes written as eicosapentaenoic docosahexenoic (DHA) 22:6 D4,7,10,13,16,19 (n-3) Note: sometimes written as docosahexaenoic 5/11

6 There is an alternative to the symbolic representation of fatty s, in which the Cs are numbered from the distal end (the n or w end) of the acyl chain (the opposite end from the carboxyl group). Hence 18:3 D9,12,15 could be written as 18:3 (w -3) or 18:3 (n -3) where the terminal C is numbered one and the first double bond starts at C3. Arachidonic is an (w -6) fatty while docosahexaenoic is an (w -3) fatty. Note that all naturally occurring double bonds are cis, with a methylene spacer between double bonds - i.e. the double bonds are not conjugated. For saturated fatty s, the melting point increases with C chain length, owing to increased likelihood of van der Waals (London or induced dipole) interactions between the overlapping and packed chains. Within chains of the same number of Cs, melting point decreases with increasing number of double bonds, owing to the kinking of the acyl chains, followed by decreased packing and reduced intermolecular forces (IMFs). Fatty composition differs in different organisms: animals have 5-7% of fatty s with carbons, while fish have 25-30% animals have <1% of their fatty s with 5-6 double bonds, while plants have 5-6% and fish 15-30% Many studies support the claim the diets high in fish that contain abundant n-3 fatty s, in particular EPA and DHA, reduce inflammation and cardiovascular disease. n-3 fatty s are abundant in high oil fish (salmon, tuna, sardines), and lower in cod, flounder, snapper, shark, and tilapia. The most common polyunsaturated fats (PUFAs) in our diet are the n-3 and n-6 classes. Most abundant in the n-6 class in plant food is linoleic (18:2n-6, or 18:2 D9,12 ), while linolenic (18:3n-3 or 18:3 D9,12,15 ) is the most abundant in the n-3 class. These fatty s are essential in that they are biological precursors for other PUFAs. Specifically, linoleic (18:2n-6, or 18:2 D9,12 ) is a biosynthetic precursor of arachidonic (20:4n-6 or 20:4 D5,8,11,14 ) linolenic (18:3n-3, or 18:3 D9,12,15 ) is a biosynthetic precursor of eicosapentaenoic (EPA, 20:5n-3 or 20:5 D5,8,11,14,17 ) and to a much smaller extent, docosahexaenoic (DHA, 22:6n-3 or 22:6 D4,7,10,13,16,19 ). These essential precursor fatty s are substrates for intracelluar enzymes such as elongases, desaturases, and beta-oxidation type enzymes in the endoplasmic reticulum and another organelle, the peroxisome (involved in oxidative metabolism of straight chain and branched fatty s, peroxide metabolism, and cholesterol/bile salt synthesis). Animals fed diets high in plant 18:2(n-6) fats accumulate 20:4(n-6) fatty s in their tissues while those fed diets high in plant 18:3(n-3) accumulate 22:6(n-3). Animals fed diets high in fish oils accumulate 20:5 (EPA) and 22:6 (DHA) at the expense of 20:4(n-6). Recent work has suggested that contrary to images of early hominids as hunters and scavengers of meat, human brain development might have required the consumption of fish which is highly enriched in arachidonic and docosahexaenoic s. A large percent of the brain consists of lipids, which are highly enriched in these two fatty s. These s are necessary for the proper development of the human brain, and in adults, deficiencies in these might contribute to cognitive disorders like ADHD, dementia, and dyslexia. These fatty s are essential in the diet, and probably could not have been derived in high enough amounts from the eating of brains of other animals. The mechanism for the protective effects of n-3 fatty s in health will be explored later in the course when we discuss prostaglandin synthesis and signal transduction. Saturated fatty chains can exist in many conformations resulting from free rotation around the C-C bonds of the acyl chains. A quick review of the conformations of n-butane shows that the energetically most favorable conformation is one in which the two CH 3 groups attached to the 2 methylene C s (C2 and C3) are trans to each other, which results in decreased steric strain. Looking at a Neuman projection of n-butane shows the dihedral or torsional angle of this trans conformation to be 180 degrees. When the dihedral angle is 0 degrees, the two terminal CH 3 groups are syn to each other, which is the conformation of highest energy. When the angle is 60 (gauche+) or 300 (gauche-) degrees, a higher, local minimum is observed in the energy profile. At a given temperature and moment, a population of molecules of butane would consist of some in the g+ and g- state, with most in the t state. The same applies to fatty s. To increase the number of chains with g+tg- conformations, for example, the temperature of the system can be increased. w-3 and w-6 News from the U. Mn. Glycerophospholipid and Sphingolipids The generic structures of glycerophospholipid is show below, along with the most common glycerophospholipids. Learn the structures of phosphatic (PA), phosphatidyethanolamine (PE), phosphatidylcholine (PC) which is often called lechitin, phosphatidylserine (PS) which is often called cephalin, and sphingomylein (shown in an earlier figure). 6/11

7 Jmol: di-18:0 PC Jmol: Triacylglyceride Other Lipid Models Pre-Class Questions Lipid Structure: A. Lipid Structure - Question Triacylglyceride/Phospholipid Stereochemistry Glycerol is an achiral molecule, since C2 has two identical substituents, -CH 2 OH. Glycerol in the body can be chemically converted to triacylglycerides and phospholipids (PL) which are chiral, and which exist in one enantiomeric form. How can this be possible if the two CH 2 OH groups on glycerol are identical? It turns out that even though these groups are stereochemically equivalent, we can differentiate them as follows. Orient glycerol with the OH on C2 pointing to the left. Then replace the OH of C1 with OD, where D is deuterium. Now the two alcohol substituents on C1 and C3 are not identical and the resulting molecule is chiral. By rotating the molecule such that the H on C2 points to the back, and assigning priorities to the other substituents on C2 as follows: OH = 1, DOCH 2 = 2, and CH 2 OH = 3, it can be seen that the resulting molecule is in the S configuration. Hence we say that C1 is the pros carbon. Likewise, if we replaced the OH on C3 with OD, we will form the R enantiomer. Hence C3 is the pror carbon. This shows that in reality we can differentiate between the two identical CH 2 OH substituents. We say that glycerol is not chiral, but prochiral. (Think of this as glycerol has the potential to become chiral by modifying one of two identical substituents.) Figure: Glycerol - A prochiral molecule 7/11

8 We can relate the configuration of glycerol above (when OH on C2 is pointing to the left) to the absolute configuration of L-glyceraldehyde, a simple sugar (a polyhydroxyaldehyde or ketone) and another 3C glycerol derivative. This molecule is chiral with the OH on C2 (the only chiral carbon) pointing to the left. It is easy to remember that any L sugar has the OH on the last chiral carbon pointing to the left. The enantiomer (mirror image isomer) of L-glyceraldehyde is D-glyeraldehyde, in which the OH on C2 points to the right. Biochemists use L and D for lipid, sugar, and amino stereochemistry, instead of the R,S nomenclature you used in organic chemistry. The stereochemical designation of all the sugars, amino s, and glycerolipids can be determined from the absolute configuration of L- and D-glyceraldehyde. The first step in the in vivo (in the body) synthesis of chiral derivatives from the achiral glycerol involves the phosphorylation of the OH on C3 by ATP (a phosphoanhydride similar in structure to acetic anhydride, an excellent acetylating agent) to produce the chiral molecule glycerol phosphate. Based on the absolute configuration of L-glyceraldehyde, and using this to draw glycerol (with the OH on C2 pointing to the left), we can see that the phosphorylated molecule can be named L-glycerol-3-phosphate. However, by rotating this molecule 180 degrees, without changing the stereochemistry of the molecule, we don't change the molecule at all, but using the D/L nomenclature above, we would name the rotated molecule as D-glycerol-1-phosphate. We can t give the same molecule two different names. Hence biochemists have developed the stereospecific numbering system (sn), which assigns the 1-position of a prochiral molecule to the group occupying the pros position. Using this nomenclature, we can see that the chiral molecule described above, glycerol-phosphate, can be unambiguously named as sn-glycerol-3-phosphate. The hydroxyl substituent on the pror carbon was phosphorylated. Figure: The biological synthesis of triacylglycerides and phosphatidic from prochiral glycerol 8/11

9 The enzymatic phosphorylation of prochiral glycerol on OH of the pror carbon to form sn-glycerol-3-phosphate is illustrated in the link below. As we were able to differentiate the 2 identical CH 2 OH substituents as containing either the pros or pror carbons, so can the enzyme. The enzyme can differentiate identical substituents on a prochiral molecule if the prochiral molecule interacts with the enzyme at three points. Another example of a prochiral reactants/enzyme system involves the oxidation of the prochiral molecule ethanol by the enzyme alcohol dehydrogenase, in which only the pror H of the 2 H s on C2 is removed. (We will discuss this later.) Figure: How an enzyme (glycerol kinase) transfers a PO 4 from ATP to the pror CH 2 OH of glycerol on formation of chiral triacylglycerols and phosphatidic. 9/11

10 Lipids in Archaea, Prokaryotes and Eukaryotes Do all organisms use the same lipid building blocks to construct bilayers? It turns out they don't. Life can be divided into three separate domains, Bacteria, Archaea, and Eukaryota. Studies of sequence similarities of the ribosomal RNA genes from the DNA of these cells show that archaea and eukaryota are more closely related than bacteria (also called prokaryotes). Yet there are many similarities between archaea and bacteria. Both bacteria and archaea are single-celled organisms without nuclei and internal organelles. In the past archaea were thought to belong to the prokaryotes. Yet they differ significantly in genetic structure and in their metabolic pathways. Figure: Phylogenetic Tree of Life This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license Archaea often have very unique chemistries. Members of this domain can use not only carbohydrates and fats as sources of energy, but they can also use inorganic species such as ammonium, hydrogen, and metal ions as well as organic molecules such as methane. Some (methanogens) actually make methane. Archaea were once thought to be found only in extreme environments (hence they were also called extremophiles), but in actuality they inhabit many environmental niches, including the oceans and soil. Since many do live in extreme environments, you would expect them to have evolved to synthesize stable, structural molecules. Archaea use phospholipids in the membrane bilayers, but the lipids differ in three very important ways. Instead of fatty chains, they used isoprenoid chains as the nonpolar chain. Instead of using an ester link, the isoprenoids are covalently attached to the glycerol backbone with an ether link, which is obviously more stable than an ester bond used in the phospholipids discussed above. 10/11

11 Finally, the stereochemistry of the phospholipids is based on L-glyceraldehyde, not D-glyceraldehyde. Lipid + Genomics = Lipomics Nature Lipidomics Gateway Lipid Metabolites and Pathways Strategies (LIPID MAPS) Lipids: General Chime: Other Lipid Models Lipid Molecules References 1. Mescar and Koshland. A new model for protein stereospecificity (other than 3 point binding). Nature. 403, pg 614 (2000) Contributors Prof. Henry Jakubowski (College of St. Benedict/St. John's University) Copyright 2015 BioWiki Powered by MindTouch UC Davis GeoWiki by University of California, Davis is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 United States License. Permissions beyond the scope of this license may be available at copyright@ucdavis.edu. Terms of Use 11/11