Introduction to Lipids

1. Introduction to Lipids • Functions • Classifications • Simple lipids • Complex lipids • Precursor and derived lipids • Complex lipids incorporate • Phospholipids • Glycerophospholipids • Sphingophospholipids • Glycolipids • Other complex lipids

2. More Introduction • Saturated lipids • Unsaturated lipids • Nomenclature • Essential and non-essential fatty acids • Specialized fatty acids: PG’s and related compounds

3. Lipids • Insoluble or poorly soluble in water • Soluble in non-polar solvents • Water-hating nature is due to the predominance of hydrocarbon chains • Functions • As a storage form of metabolic fuel • As a transport form of metabolic fuel • They provide structural composition of membranes • They have protective functions in bacteria, plants, and insects serving as a part of the outer coating between the body of the organism and the environment

4. Classification • Simple: Esters of fatty acids with alcohols • Complex: • Phospholipids = Fatty acid + Alcohols +Phosporic • Glycolipids = Fatty acid + Sphingosine + Cholesterol • Others = Sulfolipids, Amino lipids • Precursor and derived lipids: • Fatty acids, vitamins, hormones • Fatty acids are water insoluble long-chain hydrocarbons

5. Saturated and Unsaturated Lipids • Saturated fatty acids have no double bond. • General formula: CH3(CH2)n-COOH • The systematic name gives the number of carbons with the suffix anoic. For example, palmitic acid has sixteen carbons and the systematic name is hexadecanoic. • Unsaturated fatty acids have one or more double bonds. • Enoic is the suffix used. • Octadecenoic • Oleic acid unsaturated • Double bond are nearly always found in thecis configuration.

6. Space Filling Models of Palmitate and Oleate

7. Nomenclature • 20:4 (5,8,11,14) = Arachidonic acid • This is a tetraenoic acid (four double bonds). • The carbon atoms are numbered with the –COOH carbon counted as C #1.

8. Fatty acids structural formulas and space filling models

9. Space filling models of Sphingomyelin (A) and phosphatidyl choline (B) A. B.

14. There are 3 types of membrane lipids • 1. Phospholipids • 2. Glycolipids • 3. Cholesterol

15. Phospholipids • Phospholipids are the major class of membrane lipids. • Phospholipids are the most abundant lipids in membranes. • They are derived from glycerol (3 C alcohol) or sphingosine (complex alcohol). • Phospholipids derived from glycerol are called phosphoglycerides. • Components of a phosphoglyceride: Glycerol backbone (two fatty acids attached to) and phosphorylated alcohol. Fatty acid --- GLYCEROL --- P --- Alcohol

16. Schematic structure of a phospholipid

17. More Phospholipids • The length and the degree of unsaturation of fatty acid chains in membrane lipids have a profound effect of membrane fluidity. • In general, increasing the chain length will increase the melting temperature, Tm, of a fatty acid. • Addition of double bonds will decrease the Tm. • Therefore, the presence in membrane lipids of fatty acid’s that contain double bonds helps maintain the fluid nature of those lipids. • At physiological PH, the COOH (PKg = 4.8) ionizes, becoming COO-. It has an affinity for H2O. It gives fatty acid’s amphipathic nature. • The longer the fatty acid chain the more hydrophobic the chain is. • Since most of them are long-chain fatty acids, and highly insoluble in water, they are transported in the circulation with ALBUMIN.

18. Still More Phospholipids • Because they are ionized at physiological PH, two common fatty acids • Palmitic  Palmitate (C16) • Oleic  Oleate (C18, one double bond) • 1CH2OH - 2CH2OH - Glycerol 3CH2OH - The OH on 1 and 2 are esterified to the COOH groups of two fatty acids and 3 has PO32-. • Phosphatidate: simplest phosphoglyceride and key intermediate in the biosynthesis of the other phosphoglycerides.

20. Common Alcohol Moieties of Phophoglycerides

28. Membrane lipids • Sphingomyelin is a phospholipid found in membranes that is not derived from glycerol. Instead the backbone in sphingomyelin is sphingosine, an amino alcohol that contains a long, unsaturated hydrocarbon chain. In sphingomyelin, the amino group of the sphingosine backbone is linked to a fatty acid by an amide bond. • Glycolipids, as their name implies, are sugar-containing lipids. Like sphingomyelin, the glycolipids in animal cells are derived from sphingosine. The amino group of the sphingosine backbone as acylated by a fatty acid, as in sphingomyelin.

29. Sphingolipids, etc. • Sphingomyelin is the only phospholipid in membranes that is not derived from glycerol. Instead, the backbone is sphingosine, an amino alcohol that contains a long, unsaturated hydrocarbon chain. • Are found in large quantities in brain and nerve tissue… • On hydrolysis… • No glycerol is present… • Many membranes also contain glycolipids and cholesterol. • Are sugar containing lipids • Cell surface carbohydrates • Derived from sphingosine • Contain ceramide and one or more sugars • Look like sphingomyelin… instead of phosphoryl choline, they have a sugar unit…

31. Steroids • Steroids play many physiologically important roles. • Cholesterol is the best known. • This sterol is present in eukaryotes but not in most prokaryotes because cholesterol evolved after the Earth’s atmosphere became aerobic. • Important steroids include: • Bile acids • Adrenocortical homrone • Sex hormones • D vit • Cardiac glycosides, etc. • Cholesterol

32. More Steroids Cholesterol • Plasma membranes are rich in cholesterol. • It occurs in animal fats but not in plant fats. • Most highly decorated small molecule. Ergosterol • A precursor of Vitamin D. • Lipid peroxidation • Serparation of Lipids. • Oil : water interfaces

33. Cholesterol

35. Membrane Structure and Dynamics • Common features of biological membranes • Major membrane lipids: phospholipids, glycolipids, and cholesterol. • Dynamic properties of the membrane • Membrane proteins • Lipid vesicles (liposomes) • Antibiotics as carriers or channels • Permeability of lipid bilayers • Membrane fluidity • Carbohydrates in the membrane, glycophorin • Transmembrane helices, spectrin*

36. Common Features of Biological Membranes • Sheet-like structures 6-10 nm thick form closed boundaries between different compartments. • Consist mainly of lipids and proteins and chs are attached to them. • Lipids have hydrophobic and hydrophilic moiety. They form closed biomolecular sheets in aqueous environment. • Globular proteins are embedded in the membrane. They serve as pumps, channels, receptors, energy transducers, and enzymes. • Membranes are non-covalent assemblies. • Most membranes are electrically polarized. • Membranes are asymmetric. • The individual lipid and protein subunits in a membrane form the fluid mosaic.

37. Lipid Vesicles and Planar Membranes • Permeability of lipid bilayers can be measured by two model systems: • Lipid vesicles (liposomes) • Planar bilayer membranes • We can make liposomes experimentally. These liposomes can be used to deliver drugs into certain cells. • Lipid bilayers are highly impermeable to ions and most polar molecules. • Transport antibiotics are carriers or channels. • Proteins in membranes: membrane proteins span the lipid bilayer.

38. Lipid bilayer

39. Principal classes of storage and membrane lipids

40. Red-blood-cell plasma membrane: An EM micrograph of a preparation of plasma membranes from RBCs

41. Representations of membrane lipids

42. Diagram of a section of a micelle: ionized fatty acids readily form such structures.

43. Lipid bilayer membrane

44. Space-filling model of lipid bilayer membrane

45. LIPOSOME

46. Preparation of glycine-containing Liposomes: Liposomes containing Gly are formed by sonication of phospholipids in the presence of Gly. Free Gly is removed by gel filtration.

47. Experimental lipid bilayer preparation

48. Permeability coefficients (P) of ions and molecules in a lipid bilayer. The ability of molecules to cross a lipid bilayer spans a wide range of values.

49. SDS-PAGE pattern of : A. Red blood cells B. Retinal cells C. Sarcoplasmic reticulum membrane Membranes differ in their protein content!

50. The Asymmetry of the Lipid Bilayer Membrane