1. CHEM Biochemistry
Chapter 10:
Lipids

2. Knowledge/ skills
Entire chapter- All except for most of Lipids as signals, cofactors and pigments
Storage lipids
Structural lipids in membranes
Vitamins A and D are hormone precursors
Vitamins E and K and the lipid quinones are oxidation/reduction cofactors

3. General information Insoluble in water
Principal energy storage ( fats and oils)
Phospholipids and sterols are structural elements of biological membranes
Other as cofactors, electron carriers, light absorbing pigments, hydrophobic anchors for proteins
Chaperones for membrane folding
Emulsifying agents in digestion
Many lipids play a passive role for energy storage or as a barrier, some are active and play a role as messengers or signalling molecules such as hormones
Some of the active roles played by lipids in the cell, apart from signalling include enzyme cofactors in electron transfer reactions, in transfer of sugar groups in glycosylation reactions, when they contain conjugated double bonds they may be involved in pigment molecules that can absorb light in vision and photosynthesis, or serve to add color such as in pumpkin

4. Storage lipids Fatty acids- Complete oxidation to CO2 and H2O
Carboxylic acids with hydrocarbon chains ranging from 4-36 carbons
Chain can be branched/unbranched
Chain can be saturated/ unsaturated
May contain ring structures

5. naming Simplified Chain length:number of double bonds
Double bond position given by a Δ followed by the number of the carbon which is participating in the double bond. Note that the carboxyl group carbon is C-1
E.g. 20:3(Δ3,9,12) denotes a carboxylic acid with 20 carbons and 3 double bonds between C-3 and C4; C-9 and C-10; C-12 and C-13
Most commonly occurring have even numbers with unbranched chains- results from the fact that in biological systems the chains are put together from two Carbon (acetate) units

6. Many double bonds are Δ9, 12,15 in the cis configuration
Almost never see alternating single and double bonds but separated by a methylene group
Trans fatty acids produced by fermentation in diary animals and hydrogenation of fish or vegetable oils- these increase the levels of LDL or bad cholesterol and decrease the levels of HDL or good cholesterol

9. Physical properties – solubility in water
Largely determined by chain length and degree of saturation of the hydrocarbon chain
Longer fatty acyl chain- less soluble
Fewer double bonds- less soluble
Compare the solubility of lauric acid (12:0, Mr200) 0.063mg/ml vs glucose (Mr 180) 1,100 mg/ml
Carboxylic acid group is polar and ionized at pH7 and accounts for the slight solubility of the shorter chain fatty acids in water.

10. Physical properties- melting point
Influenced by length and degree of unsaturation of the hydrocarbon chain
At room temp the saturated fatty acids from 12:0 to 24:0 are waxy while the corresponding unsaturated fatty acids are oily liquids
Differences due to the degree of packing of the molecules
In fully saturated molecules, large degree of free rotation around the C-C backbone and very flexible and able to pack tightly into nearly crystalline arrays with atoms in contact all along their length
Unsaturated- cis double bond forces a kink in the hydrocarbon chain- result is that cannot pack as tightly as the fully saturated form. Overall van der Waal’s interactions less in unsaturated so less thermal energy to break bonds hence have lower melting points

12. In vertebrates, free fatty acids with a free carboxylate group are bound to a protein carrier called serum albumin
Fatty acid derivatives such as esters or amides lack the charged carboxylate group and are less soluble than free fatty acids.

13. Tri acyl glycerols
Composed of fatty acids linked to glycerol- by what linkage?

14. Ester linkage due to formation of a condensation bond
Simple if all acids are the same, e.g. tristerin
Most are mixed
What happens if you shake oil and water together?
Polar groups of both glycerol and fatty acid are linked so triacylglycerols are nonpolar, hydrophobic and insoluble
Lower specific gravity- float on water

15. Triacylglycerol function
Energy storage in adipocytes as fat droplets
Oils in plant seeds to provide energy and precursor molecules for germination
The carbon atoms of fatty acids are more reduced than carbohydrates so that more than twice the energy (gram for gram) is yielded
Because the molecule is hydrophobic, do not need water of hydration associated with polysaccharides (2g per gram of polysaccharide)
Carbohydrates are a quick energy source and are readily soluble in water
Fats are better for long term storage
Fats are good insulators against cold temperatures especially in animals that live in the cold or hibernate
Help with maintaining neutral buoyancy in diving animals like whales

16. There are 4 adipocytes in this picture
Can you tell where they are?
Storage lipids can make up more than 80% of the adipocyte dry cell mass

17. The sperm whale
Sperm whale’s head accounts for over 1/3 of its body weight. About 90% made up of spermaceti organ that is filled with spermaceti oil. The oil helps the animal maintain neutral buoyancy at ocean depths where it hunts its food and is able to change density depending on temperature

18. Saturation of oils
Many vegetable oils such as corn and olive oil are composed of triacylglycerols with unsaturated fatty acids- liquid at room temp
Hydrogenation reduces some double bonds to single bonds and can give trans double bonds
Exposure of lipids to air results in oxidative cleavage of double bonds to produce aldehydes and shorter chain carboxylic acids that are more volatile and smell rancid

20. Waxes
Esters of long chain (C14 to C36) saturated and unsaturated fatty acids with long chain alcohols
Melting points (60ºC – 100ºC)
Can be used as a metabolic fuel store
Provide water repellent properties- help to waterproof
Lubricate hair and skin
Protect against parasites
E.g. lanolin, beeswax, carnuba wax

22. Lipid types
This is an important overall picture of the lipids and how they are built

23. Lipids in membranes
Membranes serve as a barrier to passage of polar molecules and ions
The molecules are amphipathic, one end is hydrophobic and the other is hydrophilic
The hydrophilic end interact with water on either side of the membrane- can be a single OH or more complex as in the phospholipids, or sugars as in the glycolipids
The hydrophobic end interact with each other in a bilipid layer structure
Membrane lipids can make up 5 to 10% of the dry mass of cells

24. Glycerophospholipid Aka phosphoglyceraldehydes
Two fatty acids attached via ester linkage to C-1 and C-2 of glycerol
Polar or charged group attached via a phosphodiester linkage to C-3 with an alcohol
Di acyl-glycerol

25. Head group substituents
Groups named as derivatives of the parent compound, with phosphatidic acid as the parent compound. Polarity of the group gives a charge and these contribute to a large extent the charge of the membrane surface.
Note that something like phosphatidy choline has the choline group at the C-3 position, and any number of different fatty acids at the C-1 and C-2 positions. The composition of the fatty acid groups is organism specific, tissue specific and can even be cell specific- generally contain C16 toC18 saturated at C-1 and C18 to C20 unsaturated at C-2

27. Ether lipids Alkyl ether lipid- saturated
Plasmalogen- double bond between C-1 and C-2
Functional use not known, but these are resistant to cleavage by phospholipases which cleave ester linked fatty acids

28. An example of ester and ether linkage
Molecular signal to stimulate platelet aggregation

29. Galactolipids
One or two galactose residues connected by a glycosidic linkage to C-3 of a 1,2 diacylglycerol
Important in plant thylakoid membranes.

31. Sulfolipids
Sulfonate group bears a negative charge like a phosphate group

32. Glycerol dialkyl glycerol tetraether
Found in archaebacteria- live in extreme conditions of pH and temperature
Molecule is longer (32C) to make a membrane with a hydrophobic core and hydrophilic ends (glycerol)
Ether bond linkage more stable to hydrolysis than ester bond

33. Sphingolipids
Polar head group but use the long chain amino alcohol sphingosine instead of glycerol
Has one long chain fatty acid
Has a polar head group linked by a glycosidic linkage or phosphodiester linkage
Use sphingosine or a sphingosine derivative
Ceramide has a fatty acid attached in amide linkage to NH2 on C-2 which is structurally similar to diacylglycerol. Ceramide is the structural parent of the sphingolipids

34. Shingomyelins have phosphocholine or phosphoethanolamine and are classified as phospholipids. Note that the the molecule has no overall charge in spite of having a negative charge on one of the oxygens associated with the phosphorous and a positive charge associated with the Nitrogen. These are found in the plasma membrane of neurones in their myelin sheath surrounding and insulating the neurons
Glycosphingolipids occur on the outer face of plasma membranes and have a sugar connected to the C-1 OH. Do not contain phosphate. Cerebrocides have one sugar attached. Galactose is found in neural tissue and glucose in non-neural tissue.
Globosides are neutral with two or more sugars (D-glucose, D-galactose, N-acetyl-D-glucosamine). Both globosides and cerebrocides have no net charge at pH7.
Gangliosides have one or more residues of N-acetylneuraminic acid giving them a net negative charge at pH7. GM (mono) have one residue; GD (di) have two residues etc
One major use of sphingolipids is for cell recognition on the cell surface. The carbohydrate groups define human blood groups.
Kinds and amounts of gangliosides change with induction of tumors in neuronal tumor cells

37. Breakdown of membrane lipids
Membrane lipids continuously made/broken
Specific enzymes attack each hydrolyzable bond
Defects in these enzymes lead to severe consequences (Tay-Sachs)
Tay-Sachs disease caused by a ganglioside GM2 accumulates in the brain and spleen causing progressive mental retardation, paralysis, blindness and death by age 3 or 4. the enzyme hexosaminidase in lacking

38. Diseases associated with problems in breaking down sphingolipids

39. Sterols- e.g cholesterol
Have 4 fused Carbon rings, three 6 carbon and one 5 carbon to form the steroid nucleus- rigid and planar
Present in eukaryotic cells
Cholesterol is ampiphatic
Are precursors for steroid hormones which regulate gene expression
Bacteria cannot synthesize sterols
Sterols found in plants and fungi
Use bile acids (a cholesterol derivative) to act as a detergent in the intestine to help emulsify fats for digestion
Steroid hormones lack the alkyl chain attached to ring D of cholesterol and are more polar than cholesterol

40. Examples of sex hormones

41. Vitamin A, D, E and K Fat soluble vitamins
All are isoprenoid compounds synthesized by condensation of multiple isoprene units
Vitamin A and D are hormone precursors

42. 1,25-dihydroxycholecalciferol- a hormone that regulates calcium uptake in the intestine and Ca levels in kidney and bone; regulates gene expression to turn on synthesis of Ca 2+ binding protein
Vitamin D2 (ergocalciferol) is similar to D3 and is added to milk and butter as a dietary supplement

44. Vitamin A (retinol), hormone and visual pigment
Retinoic acid regulates gene expression in development of epithelial tissue including skin
Retinal is a vitamin A derivative that is used as a pigment in the rods and cones of the eye.
Vitamin A deficiency involved in skin dryness, retarded development and growth, night blindness

45. Vitamin E- collective name for tocopherols
Contain a substituted aromatic ring and long isoprenoid side chain.
Are hydrophobic and associate with membranes, lipid deposits and lipoproteins
Aromatic ring destroys free radicals to protect fatty acids from being oxidized
Found in eggs, vegetable oils and wheat germ

46. Vitamin K
Undergoes oxidation and reduction during active prothrombin formation.
Prothrombin splits the peptide bonds in fibrinogen to fibrin an insoluble protein that holds blood clots together