LIPIDS

1. LIPIDS • It is almost impossible to watch TV ads without some company talking about fats and dieting. We’re familiar with that, but we still crave the foods that contain fats and still know very little about them.

2. FATTY ACIDS – LIPID BUILDING BLOCKS • TRIACYLGLYCERIDES & PHOSPHOLIPIDS • SPHINGOMYELINS (NOT VERY DIFFICULT) • CHOLESTEROL & FRIENDS (STEROIDS)

3. Essential information: Fats are lipids, but NOT ALL LIPIDS ARE FATS. Both substances are soluble in non-polar solvents -- like benzene and xylene (liquids used in organic chemistry). However, the terms lipids and fats have different meanings. Fats are esters formed from fatty acids and the compound glycerol. Animals use fats for energy storage and insulation. Lipids are compounds soluble in a non-polar solvents, but they don’t have to be esters.

4. So a lipid could include stuff like gasoline or jet engine fuel (specially formulated kerosene) or even be in that material in our bodies that the weight reduction people call “cellulite” (tissue composed of cells full of triacylglerols, a type of fat). We have to be careful how the terms are used. All the compounds used in this course are all accurately called lipids.

5. SOME EXAMPLES OF LIPIDS: This lipid is a fat.

6. WHY ARE LIPIDS IMPORTANT? • They are a significant source of fuel/ energy. • They form borders for cells and within cells. • They are sources of hormones & vitamins.

7. t TRIACYLGLYEROLS HEART TISSUE OTHER TISSUES (STARVATION) INSULIN DEPENDENT TISSUES (DIABETES) PHOSPHOLIPIDS FORM/ MAINTAIN PLASMA CHOLESTEROL MEMBRANES AND SUB-CELLULAR ORGANELLE BOUNDARIES CHOLESTEROL PRECURSOR FOR MANY HORMONES

8. LIPID SOLUBILITY CHARACTERISTICS IT GOES WITHOUT SAYING THAT LIPIDS ARE SOLUBLE IN NON-POLAR SOLVENTS. THAT IS, THERE IS NO PARTIAL CHARGE IN ANY PART OF A LIPID SOLVENT SUCH AS IS FOUND IN WATER. ENERGETICALLY, LIPIDS ARE STABLE IN NON-POLAR SOLVENTS AND THEY ARE CALLED “HYDROPHOBIC” – WATER HATING COMPOUNDS. OF COURSE, THERE ARE EXCEPTIONS. SOME LIPIDS HAVE A PORTION OF THEIR COMPOSITION THAT IS COMPATIBLE WITH WATER (CHARGED REGIONS). SUCH LIPIDS ARE CALLED “AMPHIPATHIC” – DUAL ROLES. H H O d+ d+ d-

9. What exactly is a hydrophobic bond? • It is not a true bond, but an association • of non-polar compounds made to • minimize their contact with a polar • solvent. This is energetically favorable • for the polar solvent. • It helps if the non-polar compound • (such as a lipid) has some hydrophilic • region(s). • The micelle structure to the right  • is composed of fatty acids in which • the alkyl groups are buried inward • the carboxyl groups interact with • the polar water molecules. • What if there are no hydrophilic regions?

10. TWO NON-POLAR SOLVENTS ARE SHOWN HERE: CH3 CH3 HEPTANE CYCLOHEXANE TWO PARTIALLY POLAR LIPIDS ARE SHOWN HERE: POLAR ENDS PALMITIC ACID OLEIC ACID

11. Fatty acids: lipid building blocks • Fatty acids have two parts: a hydrocarbon tail and a carboxylic head CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COO- H+ DODECANOIC ACID or LAURIC ACID Greek = 12 (dodekanos = dodekanos) Latin = laurel plant (laurus)

13. FATTY ACID FACTS: • FA have both IUPAC (systematic) & common names. • FA partially deionize. • Most biological FA are 12-24 carbons long. • FA are either completely saturated or have one or more double bonds. •  carbon length -  melting point •  unsaturation -  melting point

14. Here are the effects of saturation and carbon lengths on melting points of fatty acids

15. SOME SHORTHAND NAMING: • Short-hand methods for naming FA begin with either the carboxylic acid end or the methyl end of the molecule: lauric acid = 12:0; oleic acid = 18:1 linolenic acid = 18:3 D9,12,15 • (This is also an w-3 fatty acid) • 18:3 indicates an 18C fatty acid with three double bonds; • D9,12,15 shows the positions of the double bonds; • and w-3 states the double bond begins at C3 from the • methyl group (opposite of the carboxyl group)

16. This is an example of an omega-3 fatty acid.

17. Commercial hydrogenation converts FAs in the cis configuration (shown on the left) into saturated FA. However, side reactions also produce trans FA (shown on the right). Trans FA increase LDL* lipids in the body that cause a buildup of arterial lipid deposits leading to atherosclerosis. *low density lipoprotein (containing so called “bad” cholesterol)

18. SATURATED VS. UNSATURATED FA • There is a wide variety of FA consumed in our diets and it depends on the source of the lipids.

19. There are two issues, then, concerning • the consumption of FA in the diet: • excessive intake of saturated FA • (beef and butter as examples) • excessive intake of trans-FA • (margarine made by hydrogenation) • Some oils that tend to be low in saturated and • trans-FA are canola, olive and flax seed.

20. Analysis of Fatty Acids: Treat (b) and (c) With NaOH and methanol to produce fatty acyl methyl esters (transesterification). Process at (e) or (f).

21. STORED FAT: TRIACYLGLYCEROLS(TGs)

22. TAG FACTS • Most of the FAs in TAGs are of mixed chain length and degree of saturation (important for membrane properties). • The energy obtained by metabolic oxidation of TAGs is ~2.2x that of proteins and carbohydrates. • TAGs are an important temperature insulator for animals.

23. SAPONIFICATION(FAT HYDROLYSIS) Cells produce their own form of TG hydrol- ysis by using lipase enzymes to separate FAs prior to transporting them and combining them into new lipids.

24. STRUCTURAL FORMS OF LIPIDS • There are three types of lipids that are used to form tissue structures (membranes): • GLYCEROPHOSPHOLIPIDS • SPHINGOLIPIDS • STEROIDS (CHOLESTEROL)

25. GLYCEROPHOSPHOLIPIDS Glycerophospholipids (phospholipids) are a variation of TGs, but they substitute a polar headgroup for one of the FA parts. Shown below is phosphatidic acid:

26. TYPES AND NATURE OF HEAD GROUPS: Example – phosphatidyl choline The choline group, shown in the box, is one type of phospholipid head group that has a positive charge located on the N. This groups interacts with water on either side of a membrane.

27. OTHER POLAR HEAD GROUPS:

28. GLYCEROPHOSPHOLIPIDS ARE GLYCEROL* UNITS TO WHICH ARE ESTERIFIED: 2 FATTY ACIDS AND ONE POLAR HEAD UNIT THE FATTY ACIDS ARE COMMONLY MIXED – ONE SATURATED AND ONE UNSATURATED THE HEAD UNITS CONSIST OF SIX COMMON TYPES – CHOLINE AND ETHANOLAMINE ARE TWO OF THE MOST COMMON TYPES. *GLYCEROL IS A “HINGE MOLECULE”

29. GLYCEROPHOSPHOLIPIDS (PL) FOR • MOST OF US SERVE AS MEMBRANE • COMPONENTS PRIMARILY AND AS • FUEL SECONDARILY. • THE POLAR BEAR USES PL AS: • AN INSULATOR • A FUEL • A SOURCE OF WATER: • PL  PHG + FA  FA (- 2C)  HOH

30. SPHINGOLIPIDS THE RIDDLE OF THE SPHINX: What goes on four feet in the morning; Two feet in the afternoon; and Three feet in the evening? A CLASS OF LIPIDS WHOSE STRUCTURE PERPLEXED INVESTIGATORS WERE KNOWN AS SPHINGOLIPIDS sjiggw

31. SPHINGOLIPIDS USE SPHINGOSINE AS THEIR HINGE MOLECULE INSTEAD OF GLYCEROL.

32. Examples of some sphingolipids:

33. WHERE AND WHY ARE SPHINGOLIPIDS PRESENT? 1. ARE OFTEN FOUND IN NERVOUS MEMBRANES OF HIGHER ANIMALS. 2. SPHINGOMYELIN IS ALSO FOUND IN MUSCLE MEMBRANES. 3. GLYCOSPHINGOLIPDS ARE ALSO IMMUNOMARKERS FOR CELLS.

34. A NOTE TO CONSIDER: THE DEGRADATION OF GANGLIOSIDES OCCURS IN LYSOSOMES AND IS AN IMPORTANT PROCESS. IF A DEFICIENCY IN ONE OR MORE DEGRADATIVE ENZYMES OCCURS THERE, THEN A DISEASE KNOWN AS A METABOLIC STORAGE DISEASE MAY OCCUR. AN EXAMPLE IS TAY-SACH’S DISEASE IN WHICH A GANGLIOSIDE (GM2) IS ONLY PARTIALLY DEGRADED DUE TO THE DEFICIENCY OF THE ENZYME: HEXOS- AMINIDASE A. THE EXCESS LIPID CAUSES MENTAL RETARDATION AND EVENTUALLY DEATH.

35. ISOPRENE & CHOLESTEROL • A final consideration with lipids and membranes is with the steroid known as cholesterol (no fatty acid components here). • Cholesterol is synthesized from terpene units known as isoprene:

36. ISOPRENE IS A DANGEROUS • LIPID: • IT IS A COLORLESS LIQUID • HIGHLY INFLAMMABLE • OBTAINED FROM REFINING OIL • STARTING MATERIAL FOR • MAKING SYNTHETIC RUBBER • BUT, IN THE BODY – • IT IS MADE FROM acetyl CoA

37. SOME COMMONLY KNOWN TERPENES:

38. CHOLESTEROL • is a steroid - a terpenoid lipid with four fused rings. 2. is the starting molecule for hormone synthesis. 3. An important component of plasma membranes, some intracellular organelles, and blood lipoprotein complexes.

39. 2 1 • The hydroxyl group on cholesterol • is often esterified to fatty acids to • make cholesteryl esters. • 2. The methyl groups on cholesterol • can be substituted with other • groups (e. g., fluorine) and • profoundly change the properties • of the molecule. • The tail of the cholesterol molecule • is often shortened and substituted • to form hormones. 3

40. SUMMARY • FATTY ACIDS ARE THE BUILDING BLOCKS OF MOST BIOLOGICAL LIPIDS. • FATS ARE STORED AS TRIACYLGLYERIDES. • LIPIDS ARE INCORPORATED INTO MEMBRANES AS PHOSPHOLIPIDS, SPHINGOMYELINS AND CHOLESTEROL. • THE PROPERTIES OF EACH OF THESE CLASSES OF LIPIDS DETERMINES THEIR BIOLOGICAL USE.

41. IMPORTANT THINGS TO STUDY FROM THIS LECTURE: WHAT IS THE DIFFERENCE BETWEEN FAT AND LIPIDS? WHAT ARE THE BIOLOGICAL USES OF LIPIDS? ARE LIPIDS NON-POLAR? WHAT DOES THAT MEAN? WHAT GENERAL STRUCTURAL PROPERTIES DO FATTY ACIDS HAVE? HOW ARE THEY NAMED? WHAT PROPERTIES DO SATURATION/UNSATURATION GIVE TO FATTY ACIDS? WHAT ARE TRANS FATTY ACIDS? IN REFERENCE TO 6. – WHAT KINDS OF FATTY ACIDS ARE IMPORTANT IN THE DIET? HOW CAN FATTY ACIDS BE ANALYZED? WHAT IS SAPONIFICATION? HOW ARE FATS METABOLIZED IN TISSUES FOR EXAMPLE – TO PRODUCE STORAGE FORMS IN CELLS? 10. CAN YOU DISTINGUISH BETWEEN GLYCEROPHOSPHOLIPID AND SPHINGOLIPID STRUCTURES? WHERE DO THESE LIPIDS OCCUR? 11. CAN YOU GIVE SOME BASIC STRUCTURAL PROPERTIES OF CHOLESTEROL AND WHERE IT IS LOCATED IN THE BODY?