1 Lipids Lehninger 3 rd ed. Chapter 11 (For biosynthesis see Chapter 21) 2 Lipids: a Diverse group of chemicals Insolubility in water. Fats and oils: energy stores. Phospholipids and sterols: structural elements of membranes. Enzyme co-factors, electron carries, pigments, hydrophobic anchors, emulsifying agents, hormones and intracellular messengers. Storage Lipids: derivatives of fatty acids. 3 1
4 5 Saturation affects physical state 6 Fatty acids in the body Most double bonds are in the cis configuration. Double bonds are almost never conjugated: No Yes Double bonds readily oxidize, resulting in rancid oil. Due to low solubility in the blood they are bound to a carrier protein: serum albumin. Most carboxylic groups are derivatized to esters and amides. 2
7 Triacylglycerols (a.k.a triglycerides) Simplest lipid constructed from three fatty acids esterified to glycerol. Monoglycerides and diglycerides exist as well. Very hydrophobic. Lower specific gravity than water. 8 Triacylglycerols: Stored energy Triglycerides oxidation results in twice the amount of energy than carbohydrate oxidation. Minimal hydration results In more efficient storage versus carbohydrates. Moderately obese people (15-20Kg of fat) could live off their Triglycerides for months as opposed to a day off their glycogen stores. Enzymes that break down fat (lipases) are used to release the fatty acids. 9 Triacylglycerols: storage location Eukaryotic cells: oily droplets form inclusion in the aqueous cytosol. Vertebrates: adipocytes are specialized cells that store fat, located mainly under the skin Plants: located in seeds. 3
10 Adipocytes 11 Arabidopsis seed 12 Triacylglycerols: Insulation Layers of adipocytes under the skin (blubber) are used to insulate marine mammals against marked cold. Layer thickness can be up to 60cm. Is used as a storage for energy, especially in hibernating animals. Were humans once aquatic species? 4
Spermaceti Organ: 3.6 Tons of fat that control buoyancy and echo-location 13 Triglycerides in Foods 14 15 Waxes Waxes are esters of fatty acids and long chain alcohols, resulting in an extremely hydrophobic molecule: They serve as energy stores (plankton) and water repellents. 5
16 Structural lipids in Membranes The central architectural feature of the biological membrane is a double layer of lipids. There is a huge variety of types of lipids but it is nearly possible to delineate them into three classes: Glycerophospholipids Sphingolipids Sterols. 17 18 Glycerophospholipids (a.k.a. phosphoglycerides) Membrane lipids in which two fatty acids are esterified to the 1 st and 2 nd carbons of glycerol. A phosphate group is attached to the 3rd carbon of the glycerol backbone. 6
19 Glycerophospholipids head groups The phosphate can be further derivatized with a variety of head groups 20 21 Glycerophospholipids cont. Glycerophospholipids are nearly always negatively charged or zwitterionic. The large variation in head groups as well as in the fatty acids constituents, result in an amazing variety of different lipid species (the biological reason of which is mostly unknown). Due to the ester linkage, glycerophospholipids are acid labile. 7
22 Ether-linked phospholipids 23 Sphingolipids Sphingolipids are composed of the long chain amino alcohol shingosine,amidated with a fatty acid resulting in a molecule called ceramide. 24 8
25 Sphingolipid classes: There are 3 classes of Sphingolipids, all derived from ceramide: Sphingomyelins. Glycosphingolipids. Gangliosides. Sphingomyelins Sphingomyelins contain simple phosphate based head groups, similar to phosphoglycerides 26 27 Glycosphingolipids Glycosphingolipids have head-groups with one or more sugars connected directly to the ceramide. Cerebrosides have one sugar group. Globosides are neutral glycosphingolipids with two or more sugars. 9
28 Gangliosides Gangliosides are highly complex sphingolipids that contain a large oligosaccharide group with a sialic acid moiety rendering it negatively charged. They are the determinates of blood groups. 29 30 10
Sterols 31 Structural lipids based on the steroid nucleus. The steroids are planar and are thus rigid. Cholesterol is the most common animal sterol and can account for up to 50% of the membrane lipid mass. 32 Steroid hormones are sterol derivatives 33 Fatty acid biosynthesis Fatty acids are synthesized by a repeating sequence of 4 reactions which constitute a cycle. In each cycle 2 carbons units are added to the acid until it reaches 16 carbons (palmitate). Longer chain fatty acids are synthesized from palmitate by the fatty acid elongation systems. It is for this reason that all natural fatty acids contain an even number of carbons. 11
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37 38 39 Fatty acid synthase The fatty acid synthase is a complex protein complex containing 7 subunits and at least 3 other accessory proteins. The growing fatty acid is connected to the acyl carrier protein (ACP) via a long and flexible Pantothenic acid linker. The system is thought to work by rotation of the growing acid to each subunit. 13
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