lipids

•  from the greek word lipos for “fat.” •  biomolecules that are soluble in organic solvents. •  C-C and C-H bonds makes them very soluble in

organic solvents and insoluble in water.

lipids have many C-C and C-H bonds, but there is no one functional group common to all lipids.

Lipids can be categorized as hydrolyzable or nonhydrolyzable

Hydrolyzable lipids can be cleaved into smaller molecules by hydrolysis with water.

Nonhydrolyzable lipids cannot be cleaved into smaller units by aqueous hydrolysis.

Waxes  •  The simplest hydrolyzable lipids.

•  Esters (RCOOR') formed from a high molecular weight alcohol (R'OH) and a fatty acid (RCOOH).

waxes are very hydrophobic.  

Triacylglycerols  (triglycerides)    •  the  most  abundant  lipids  

•  triesters  that  produce  glycerol  and  three  molecules  of  fa9y  acid            upon  hydrolysis.  

•  Simple triacylglycerols are composed of three identical fatty acid side chains

•  mixed triacylglycerols have two or three different fatty acids.

What are the characteristics of these fatty acids?

• All fatty acid chains are unbranched, but they may be saturated or unsaturated. • Naturally occurring fatty acids have an even number of carbon atoms. • Double bonds in naturally occurring fatty acids generally have the Z configuration. • The melting point of a fatty acid depends on the degree of unsaturation.

Fats and oils are triacylglycerols (triesters of glycerol and these fatty acids). • Fats have higher melting points, making them solids at room temperature.

• Oils have lower melting points, making them liquids at room temperature.

The Most Common Fatty Acids in Triacylglycerols

Three saturated side chains lie parallel to each other, making a compact lipid.

One Z double bond in a fatty acid side chain produces a twist so the lipid is no longer so compact.  

Fatty Acid Composition of Some Fats and Oils

Hydrolysis of triacylglycerols

Hydrolysis of a triacylglycerol with water in the presence of either acid, base, or an enzyme yields glycerol and three fatty acids.

Hydrogenation of unsaturated fatty acids

Oxidation of unsaturated fatty acids

In the cell, the principal function of triacylglycerols is energy storage.

Phospholipids

•  Hydrolyzable lipids that contain a phosphorus atom. •  Two common types: phosphoacylglycerols and sphingomyelins. •  Found almost exclusively in the cell membranes of plants and

animals

The phosphorus atom in a phosphodiester shares 10 electrons. Third-row elements (such as P and S) can be surrounded by more than eight electrons.

Phosphoacylglycerols

•  Phosphoacylglycerols (or phosphoglycerides) are the second most abundant type of lipid.

•  They form the principal lipid component of most cell membranes.

There are two prominent types of phosphoacylglycerols. They differ in the identity of the R’’ group in the phosphodiester.

• When R'' = CH2CH2NH3+, the compound is called a phosphatidylethanolamine or cephalin.

• When R'' = CH2CH2N(CH3)3+, the compound is called a phosphatidylcholine, or lecithin.

A phosphoacylglycerol has two distinct regions: two nonpolar tails due to the long-chain fatty acids, and a very polar head from the charged phosphodiester.

Sphingomyelins Sphingomyelins, the second major class of phospholipids, are derivatives of the amino alcohol sphingosine, in much the same way that triacylglycerols and phosphoacylglycerols are derivatives of glycerol.

• A phosphodiester at C1. • An amide formed with a fatty acid at C2.

Fat-Soluble Vitamins Vitamins are organic compounds required in small quantities for normal metabolism. The fat-soluble vitamins are lipids.

• Vitamin A (retinol) is obtained from fish liver oils and dairy products, and is synthesized from β-carotene, the orange pigment in carrots. • In the body, vitamin A is converted to 11-cis-retinal, the lightsensitive compound responsible for vision in all vertebrates • A def ciency of vitamin A causes night blindness, as well as dry eyes and skin.

• Vitamin D3 is the most abundant of the D vitamins. It can be synthesized in the body from cholesterol. • Vitamin D helps regulate both calcium and phosphorus metabolism. • A deficiency of vitamin D causes rickets, a bone disease.

• vitamin E refers to a group of structurally similar compounds, the most potent being α-tocopherol. • Vitamin E is an antioxidant, so it protects unsaturated side chains in fatty acids from oxidation. • A deficiency of vitamin E causes numerous neurologic problems.

• Vitamin K (phylloquinone) regulates the synthesis of prothrombin and other proteins needed for blood to clot. • A defi ciency of vitamin K leads to excessive and sometimes fatal bleeding because of inadequate blood clotting.

• The electron density is distributed fairly evenly among the carbon atoms of these vitamins due to their many nonpolar C–C and C–H bonds.

Eicosanoids

Group of biologically active compounds containing 20 carbon atoms derived from arachidonic acid. The prostaglandins and the leukotrienes are two types of eicosanoids. Two others are the thromboxanes and prostacyclins.

Dinoprostone, the generic name for PGE2 , is administered to relax the smooth muscles of the uterus when labor is induced, and to terminate pregnancies in the early stages.

Prostaglandins themselves are unstable in the body, often having half-lives of only minutes, more stable analogues have been developed that retain their important biological activity longer.

•  A group of anti-infl ammatory drugs that block only the COX-2 enzyme was developed in the 1990s (rofecoxib, valdecoxib, and celecoxib)

•  Especially effective NSAIDs for patients with arthritis. •  Both rofecoxib and valdecoxib have been removed from the

market (increased risk of heart attack and stroke).

Terpenes Lipids composed of repeating fi ve-carbon units called isoprene units. An isoprene unit has fi ve carbons: four in a row, with a one-carbon branch on a middle carbon.

• An isoprene unit may be composed of C–C s bonds only, or there may be p bonds at any position. • Isoprene units are always connected by one or more carbon–carbon bonds. • Each carbon atom is part of one isoprene unit only. • Every isoprene unit has five carbon atoms. Heteroatoms may be present but their presence is ignored in locating isoprene units.

Classes of Terpenes

The Biosynthesis of Terpenes

Terpene biosynthesis is an excellent example of how syntheses in nature occur with high efficiency.

[1] The same reaction is used over and over again to prepare progressively more complex compounds.

[2] Key intermediates along the way serve as the starting materials for a wide variety of other compounds.

[1] The two C5 diphosphates are converted to geranyl diphosphate, a C10 monoterpene. Geranyl diphosphate is the starting material for all other monoterpenes.

[2] Geranyl diphosphate is converted to farnesyl diphosphate, a C15 sesquiterpene, by addition of a five-carbon unit. Farnesyl diphosphate is the starting material for all sesquiterpenes and diterpenes.

[3] Two molecules of farnesyl diphosphate are converted to squalene, a C30 triterpene. Squalene is the starting material for all triterpenes and steroids.

Biological Formation of Geranyl Diphosphate

Steps [1]–[2] Loss of the leaving group and nucleophilic attack to form a new C–C bond. Step [3] Loss of a proton

Steps [1]–[2] Isomerization of geranyl diphosphate to linalyl diphosphate

Isomerization of Geranyl Diphosphate to Neryl Diphosphate

Steroids

•  Composed of three six-membered rings and one five membered ring.

•  Many steroids also contain two methyl groups, called angular methyl groups, at the two ring junctions.

•  The steroid rings are lettered A, B, C, and D, and the 17 ring carbons are numbered as shown. The two angular methyl groups are numbered C18 and C19.

Cholesterol

•  Has  the  tetracyclic  carbon  skeleton  characteris<c  ofmsteroids.    

•  eight  stereogenic  carbons  (seven  on  rings  and  one  on  a  side  chain),    28  =  256  possible  stereoisomers.    

•  In  nature,  only  the  following  stereoisomer  exists:  

The biosynthesis of cholesterol

Two cholesterol-lowering drugs

Other Steroids

   

•  Sex hormones and the adrenal cortical steroids.

•  There are two types of female sex hormones, estrogens and progestins.

•  The male sex hormones are called androgens.

The Female and Male Sex Hormones

Estradiol and estrone are estrogens synthesized in the ovaries. They control the development of secondary sex characteristics in females and regulate the menstrual cycle.

Progesterone is often called the “pregnancy hormone.” It is responsible for the preparation of the uterus for implantation of a fertilized egg.

Testosterone and androsterone are androgens synthesized in the testes. They control the development of secondary sex characteristics in males.

Synthetic analogues of these steroids have found important uses, such as in oral contraceptives

•  Cortisone, cortisol, and aldosterone. Synthesized in the outer layer of the adrenal gland.

•  Cortisone and cortisol serve as anti-infl ammatory agents and they also regulate carbohydrate metabolism.

•  Aldosterone regulates blood pressure and volume by controlling the concentration of Na+ and K+ in body fluids.

Adrenal cortical steroids