1. Carbohydrates, nucleotides, amino acids, now lipids Lipids exhibit diverse biological function –Energy storage –Biological membranes –Enzyme cofactors –Hormones –Intracellular signals –Etc.

2. Storage lipids Fatty acids are highly reduced carbon storage forms that can be oxidized to generate energy Common lipids derived from fatty acids include –Triacylglycerols –waxes

3. Fatty acids Carboxylic acids with hydrocarbon chains ranging from 4 to 36 carbons Can be saturated (no double bonds) or unsaturated (one or more double bonds) Nomenclature specifies the chain length and number of double bonds separated by a colon (position of double bond noted with a  and superscript numbers) –Palmitic acid is abbreviated 16:0 –Oleic acid is abbreviated 18:1

5. Patterns in commonly occurring fatty acids Even number of carbon atoms (result of using acetate as building blocks) Location of double bonds (in most monounsaturated fatty acids the double bond is between C9 and C10; in polyunsaturated fatty acids additional double bonds at C12 and C15 (some exceptions)

6. Physical properties of fatty acids Determined by length and degree of unsaturation –The longer the acyl chain and fewer the double bonds, the lower the solubility in water –Melting points lower for shorter/unsaturated fatty acids The carboxylic acid group is polar (ionized at neutral pH) and helps slightly in solubility

8. Storage to structural

9. Triacylglycerols Ester linked fatty acids with a glycerol backbone Can be “simple” where all fatty acids are the same, but often mixed

10. Triacylglycerols provide insulation and storage for energy Hibernating animals generate a lot of triacyglycerols under their skin Store carbon as triacylglycerols instead of glycogen and starch –A more reduced form of carbon, get more energy (about twice) from oxidation –Hydrophobic character does not necessitate carrying water weight (water used to hydrate carbohydrates)

11. Membrane lipids Are amphipathic, pack into bilayers Include: –Glycerophospholipids –Sphingolipids –Sterols

12. Glycerophospholipids Use glycerol 3-phosphate as backbone Two fatty acids attached via ester linkage to first and second carbons, a polar or charged group is attached via a phosphodiester linkage at the third carbon

14. Ether lipids Includes membrane structural lipids of the Archaea domain

16. Sphingolipids Have a polar head group and two nonpolar tails but contain sphingosine, not glycerol Carbons 1, 2, and 3 of sphingosine are analogous to glycerol carbons When a fatty acid is attached to the –NH2 group on C2, this compound is called ceramide

18. Subclasses of sphingolipids Sphingomyelins –Contain phosphocholine or phosphoethanolamine as polar head group, prominent in myelin (hence the name) Glycosphingolipids –Modified with sugars; found in plasma membrane (recall lectins) Gangliosides –Distinct carbohydrate pattern

19. Roles for sphingolipids

20. Phospholipases breakdown phospholipids

21. Sterols Structural lipids found in most eukaryotic membranes Also serve as precursors for various biomolecules Cholesterol 

22. Other roles for lipids Phosphatidylinositol regulates cell structure and metabolism Serves as a binding site for specific proteins, and a source of extracellular messenger molecules

23. Prostaglandins regulated synthesis of intracellular messenger cAMP Oxidized sterols (steroids) serve as hormones Quinones and vitamins E and K are oxidation-reduction cofactors Fat soluble vitamins serve as cofactors, and hormone precursors –Vitamin A (retinol) was discussed before in the context of bacteriorhodopsin, and serves as a visual pigment

25. Getting energy from fat Oxidation of long-chain fatty acids to acetyl-CoA is another central energy generating pathway Electrons from this process pass to the respiratory chain, while acetyl-CoA produced during this process is further oxidized by the citric acid cycle

27. Fatty acids are activated and transported into the mitochondria

28. Distinct acyl-CoA synthetase Different enzymes have different substrate specificities for longer or shorter fatty acids All catalyze the formation of the thioester linkage between the fatty acid carboxyl group and thiol of Co-A coupled to ATP hydrolysis The reaction occurs in two steps as shown on previous slide

29. Carnitine as a carrier The fatty acyl group is transferred from CoA to carnitine, the resulting product is brought into the matrix via the acyl- carnitine/carnitine transporter

30. Linking pools of CoA The next step is transfer of the fatty acyl group from carnitine to mitochondrial CoA CoA in the mitochondrial is primarily used in oxidative degradation of pyruvate, fatty acids, and some amino acids Cytosolic CoA is also used in the biosynthesis of fatty acids

31. Transfer is rate-limiting The carnitine-mediated fatty acyl transfer is the rate-limiting step for oxidation of fatty acids and is a key regulatory point Once in the mitochondria, fatty-acyl CoA is quickly acted upon