Chapter 27. Biomolecules: Lipids Why this Chapter? Lipids are the largest and most diverse class of biomolecules To examine lipid structure, function, and metabolism

2 About Lipids Natural materials that preferentially extract into nonpolar organic solvents Includes fats, oils, waxes, some vitamins and hormones, some components of membrane General types: esters (“saponifiable”) and those that can’t be hydrolyzed

Waxes, Fats, and Oils Waxes - contain esters formed from long-chain (C16- C36) carboxylic acids and long-chain alcohols (C24-C36) Triacontyl hexadecanoate is in beeswax

4 Triacylglycerol Tri-esters of glycerol with three long- chain carboxylic acids, fatty acids.

5 Fatty Acids (from Fats and Oils) Straight-chain (C 12 - C 20 ) carboxylic acids Double bonds are cis-substituted but trans-fatty acids also occur A fat or oil in nature occurs as a mixture of many different triacylglycerols The most abundant saturated fatty acids are palmitic (C 16 ) and stearic (C 18 )

6 Unsaturated and Polyunsaturated Fatty Acids Oleic (C 18 with one C=C) and linolenic (C 18 with 3 C=C) are the most abundant unsaturated

Soap A mixture of sodium or potassium salts of long-chain fatty acids produced by alkaline hydrolysis (saponification) of animal fat with alkali

8 Cleansing Action of Soap The carboxylate end of the long-chain molecule is ionic and therefore is preferentially dissolved in water The hydrocarbon tail is nonpolar and dissolves in grease and oil Soaps enable grease to be dissolved into water

9 Detergents “Hard” water contains Mg +2 and Ca +2 that form insoluble salts with soaps Synthetic detergents are alkylbenzene sulfonates that dissolve dirt like soaps but do not form scums with Mg +2 and Ca +2.

Phospholipids Phospholipids are diesters of H 3 PO 4, phosphoric acid Phosphoric acid can form monoesters, diesters and triesters In general these are known as “phosphates”

11 Phosphoglycerides Contain a glycerol backbone linked by ester bonds to two fatty acids and phosphoric acid Fatty acid residues with C 12 –C 20 The phosphate group at C3 has an ester link to an amino alcohol

12 Sphingolipids The other major group of phospholipids Sphingosine or a dihydroxyamine backbone Constituents of plant and animal cell membranes Abundant in brain and nerve tissue, as coating around nerve fibers.

13 Phosphoglyceride Membranes Phosphoglycerides comprise the major lipid component of cell membranes Nonpolar tails aggregate in the center of a bilayer Ionic head is exposed to solvent

Prostaglandins & Other Eicosanoids C 20 lipids that contain a five- membered ring with two long side chains Present in small amounts in all body tissues and fluids Many physiological effects

15 Prostaglandin Sources Biosynthesized from arachidonic acid (C 20 unsaturated fatty acid)

Terpenoids Steam distillation of plant extracts produces “essential oils” Chemically related to compounds in turpentine (from pine sap) called terpenes and thus called terpenoids Mostly hydrocarbons (some oxygens) that do not contain esters (stable to hydrolysis)

17 Biosynthesis of Terpenoids Isopentenyl pyrophosphate (IPP) forms higher isoprenoids in reactions catalyzed by prenyl transferase Monoterpenoids, diterpenoids, and tetraterpoids arise from 1-deoxyxylulose 5-phosphate (DXP).

18 Mevalonate Pathway to Isopentenyl Diphosphate Begins with the conversion of acetate to acetyl CoA followed by Claisen condensation to yield acetoacetyl CoA Catalyzed by acetoacetyl-CoA acetyltransferase

19 Aldol Condensation Carbonyl condensation reaction of acetoacetyl CoA with acetyl CoA Produces 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)

20 Reduction HMG CoA is reduced to mevalonate Catalyzed by HMG CoA reductase utilizing NADPH

21 Phosphorylation & Decarboxylation Pyrophosphorylation gives mevalonyl-PP Addition of phosphate from ATP followed by loss of CO 2 and phosphate

22 Conversion of Isopentenyl Diphosphate to Terpenoids For triterpenes and larger, head-to-head coupling of farnesyl diphosphates gives squalene

23 Mechanism of Isomerization Isomerization of IPP to DMAPP is catalyzed by IPP isomerase through a carbocation pathway

24 Coupling Mechanism Nucleophilic substitution reaction in which the double bond of IPP behaves as a nucleophile in displacing diphosphate ion leaving group (PPO  )

25 Conversions of Monoterpenoids Typically involves carbocation intermediates and multistep reaction pathways catalyzed by a terpene cyclase

Steroids Steroids,are another class of nonsaponifiable lipid, defined by structure Has four fused rings A, B, C, and D, beginning at the lower left Carbon atoms are numbered beginning in the A ring The six-membered rings are in fixed chair conformations

27 Functions of Steroids In humans as hormones, steroids are chemical messengers secreted by glands and carried through the bloodstream to target tissues Also widely distributed as cholesterol

28 Male Sex Hormones Testosterone and androsterone are the two most important male sex hormones, or androgens Androstanedione is a precursor

29 Female Sex Hormones Estrone and estradiol are the two most important female sex hormones, or estrogens Progesterone is the most important progestin, steroids that function in pregnancy

30 Adrenocortical Hormones Adrenocortical steroids: secreted by the adrenal glands near the upper end of each kidney Mineralocorticoids: control tissue swelling by regulating cellular salt balance Glucocorticoids: regulation of glucose metabolism and in the control of inflammation

31 Synthetic Steroids Made in pharmaceutical laboratories as new drugs Includes oral contraceptives and anabolic agents Methandrostenolone is an anabolic steroid used for tissue-building

Steroid Biosynthesis Enzyme-catalyzed addition of oxygen atom to squalene Stereospecific formation of an oxirane from an alkene

1. x 2. x 3. x 4. None of these is commonly found in nature. 5. All of these are commonly found in nature. Which fatty acid is not commonly found in nature?

All of these are lipids. 5. None of these are lipids. Which of the following would not be classified as a lipid?

Which of the following describes how a soap cleans? 1. The fatty acids react with grease molecules to form water soluble compounds that are subsequently washed away. 2. The fatty acids form micelles which encapsulate grease molecules. These micelles are soluble in water and consequently washed away. 3. The fatty acids react with grease molecules to generate new compounds that can form micelles in water. These micelles are soluble in water and consequently washed away. 4. All of these statements accurately describe how soap works. 5. None of these statements accurately describe how soap works.

The following molecule would be expected to form micelles. 1. True 2. False

What forces are responsible for lipid bilayer and micelle formation? 1. covalent bonding and electrostatic interactions 2. hydrophobic effects and hydrogen bonding 3. electrostatic interactions and hydrophobic effects 4. electrostatic interactions and fluid mosaics 5. hydrophobic effects and fluid mosaics

The figure shown is: 1. phosphatidylethanolamine 2. phosphatidylcholine 3. phosphatidylserine 4. sphingosine 5. sphingomyelin

What do these two lipids have in common? 1. They are eicosanoids. 2. They form micelles in water. 3. They are prostaglandins. 4. They are steroids. 5. They are used as detergents.

Which is a role of the prostaglandins? 1. They stimulate the contraction of uterine muscle. 2. They lower blood pressure in the blood stream. 3. They suppress gastric ulceration. 4. All of these 5. None of these

The molecule shown below is a: 1. thromboxane 2. prostaglandin 3. leukotriene 4. eicosanoid 5. thromboxane and eicosanoid

The molecule shown below is: 1. lanosterol 2. camphor 3. β -carotene 4. patchouli alcohol 5. None of these

The first step of mevalonate synthesis, shown below, is a:

The 1 st step of mevalonate synthesis, shown is a: 1. Claisen condensation 2. aldol-like condensation 3. reduction reaction 4. substitution reaction 5. Schiff base formation

Why can the molecule below not be classified as a steroid? 1. Steroids cannot have double bonds. 2. Steroids cannot contain branched hydrocarbon chains. 3. Steroids have a different arrangement of rings. 4. Steroids are usually comprised of benzene rings, making them mostly flat. 5. All of these

How is cholesterol transported through the blood stream? 1. through micelles 2. through ion channels 3. by prostaglandins 4. by lipoproteins 5. as water solvated ions

In which organ of the body is cholesterol synthesized? 1. the lungs 2. the gallbladder 3. the liver 4. the kidneys 5. the pancreas

Which of the following is not a good indicator of health? 1. cholesterol levels below 200 mg/dL 2. LDL levels greater than 100 mg/dL 3. HDL levels greater than 60 mg/dL 4. active, athletic lifestyle 5. diets rich in seafood