Lipids and Fats

Why do we need fat?

Hibernating animals,Migrating birds Hormone cell membranes Bile acid Protection Vitamin Saturated fatty acids Unsaturated fatty acids Essential FAs Triacylglycerol Phospolipid Sphingolipid Sphingomyelin Lecithin Liposome

Fats (Triglyceride or triacylglycerole) To store and supply energy Lipids Phospholipids To be important membrane components Glycolipids Lipoids Cholesterol Cholesterol ester

1. Major portion of a lipid is hydrophobic due to I. Defining features of lipids 1. Major portion of a lipid is hydrophobic due to many (aliphatic) CH2 groups. 2. Minor portion is hydrophilic, allows interaction with the aqueous environment. 3. Do not exist as large polymers (unlike nucleic acids, proteins and polysaccharides). hydrophobic hydrophilic

II. Major functions of various lipid classes 1. Energy storage: fats (animals) & oils (plants) 2. Membranes: glycerophospholipids, sphingolipids, cholesterol & others in the famous lipid bilayer. 3. Specialized roles: Hormones (e.g., corticosterone) Vitamins (e.g., vitamin E) Signaling molecules (e.g., diacylglycerol)

II-1 Storage lipids: fats & oils 1. Triacylglycerols = triglycerides = fats O H2C-O-C-CH2-/\/\/\/\/\/\/\-CH3  HC-O-C-CH2-/\/\/\/\/\/\/\-CH3 glycerol is acylated to form an ester of a fatty acid O glycerol O fatty acid

H2C-O-C-CH2-/\/\/\/\/\/\/\-CH3 HC-O-C-CH2-/\/\/\/\/\/\/\-CH3 Saponification of triglycerides NaOH, water, heat Saponification value Soap H2C-OH HC-OH glycerol O-C-CH2-/\/\/\/\/\/\/\-CH3 O - free fatty acid (as a soap) (Na+ vs Mg++ or Ca++)

II-1 Storage lipids: fats & oils 2. Fatty acids (FAs) Free fatty acids in blood are mostly bound to serum albumin, an abundant blood protein. Nomenclature and size of Fats. HO-C-CH2-(CH2)13-CH3 O (1) palmitic acid: A saturated fatty acid 16:0 （2）stearic acid

(4) linoleic acid: an unsaturated fatty acid 18:2c9,12 (c=cis) HO-C-(CH2)7-CH=CH-CH2-CH=CH-(CH2)4-CH3 O 1 2-8 9 10 11 12 13 14-17 18

Classification of fatty acids Numerical Symbol Common Name Comments 14:0 Myristic acid Saturated 16:0 Palmitic acid 18:0 Stearic acid  Saturated 16:1 Δ 9 Palmitoleic acid Unsaturated 18:1 Δ 9 Oleic acid 18:2 Δ 9,12 Linoleic acid EFA 18:3 Δ 9,12,15 Linolenic acid 20:4 Δ 5,8,11,14 Arachidonic acid

Essential Fatty Acids (EFA) Linoleic, linolenic and arachidonic acids are called essential fatty acids, because they cannot be synthesized by the body and must be obtained through diet.

H2C-O-C-CH2-/\/\/\/\-CH3 HC-O-C-CH2-/\/\/\/\/-CH3 -CH2 O R-O-P-O - II.3 Membrane lipids: 1. Glycerophospholipids apolar Saturated or unsaturated FAs. Typically C16 or C18. polar CH3-N-CH2-CH2- + Phosphatidylcholine Phosphatidylethanolamine Phosphatidylserine CH3 H3N-CH2-CH2- OOC HC-CH2- H3N - R Triacyl glycerols are neutral, storage of lipids. Membrane lipids are polar.

II.3 Membrane lipids: 2. Sphingolipids HO-CH-CH=CH-(CH2)12-CH3   CH-NH-C-/\/\/\/\/\/-CH3 -CH2 O Sphingosine (blue area when R = H) fatty acid R-O R Name -H ceramide -phosphocholine sphingomyelin -monosaccharides cerebrosides -oligosaccharides gangliosides Tay Sachs disease: impaired degradation of brain gangliosides

Glycerophospholipids vs spingolipids Fig 9.7c Fig 9.10 c

II.3 Membrane lipids: 3. Cholesterol (a sterol) • common in animal membranes • precursor to several steroid hormones •VD3 Bile acid Composition of RBC membranes Protein 49% Carbohydrate 8% Lipid 43% - glycerophospholipids 48% - sphingolipids 27% - cholesterol 25% Autosynthesis:27C actyl-CoA NAPDH

Cholesterol For transport and storage, the hydroxyl group condenses with a fatty acid to form a sterol ester

Amphipathic lipid aggregates that form in water Water is excluded (b) Bilayer © When the bilayer forms in on itself, 3-d hollow vesicle with an aqueous cavity.

Cross section of a cell membrane

Lipids in the News The ‘good’ & the ‘bad’ AHA: Omega-3 fatty acids benefit the heart of healthy people, and those at high risk of — or who have — cardiovascular disease. Research has shown that omega-3 fatty acids decrease risk of abnormal heartbeats, which can lead to sudden death.  Omega-3 fatty acids also decrease triglyceride levels, lower blood pressure (slightly), and decrease rates of heart attack.

Lipids in the News II The bad: What’s the deal with trans fats? m.p. = 14 °C m.p. = 45 °C

Where do trans fats come from? Natural fats (which contain cis double bonds) are prone to oxidation and rancidity. This limits their shelf life and usefulness for food preparation. Hydrogenation (H2 + catalyst) of natural fats reduces the cis double bonds to produce saturated fats which have a longer shelf life. Unfortunately, trans bonds are produced as an unwanted by-product. The primary health risk identified for trans fat consumption is an elevated risk of coronary heart disease (CHD).

Packing of fatty acids into stable aggregates

Triacylglycerols contain three fatty acids esterified to a glycerol backbone

Triacylglycerols are stored energy in fat cells and plant seeds

The greater the percentage of saturated fatty acids in food fats the higher the melting temperature

Waxes are esters of long chain fatty acids

Common types of storage and membrane lipids

Glycerophospholipids, the main lipid component of biological membranes, contain two fatty acids esterified to a glycerol phosphate backbone

Glycerophospholipids with ether-linked fatty acids Abundant in the heart Important in inflammatory response

Glycosphingolipids as determinants of blood groups Glycosphingolipids contain the blood group antigens present on the surface of red blood cells

Bile acids are synthesized from cholesterol Bile acids aid in emulsification of dietary fat in the intestine

Other sterols are synthesized from cholesterol

Vitamin D is produced in the skin by UV irradiation of 7-dehydrocholestreol

Cystic Fibrosis This is the most common lethal genetic disease in Caucasians of Northern European ancestry, and has a prevalence of about 1:3,000 births. This autosomal recessive disorder is caused by mutations to the gene for the CF transmembrane conductance regulator (CFTR) protein that functions as a chloride channel on epithelium. Defective CFTR results in decreased secretion of chloride and increased reabsorption of sodium and water.