Reginald H. GarrettCharles M. Grisham

www.cengage.com/chemistry/garrett

Reginald Garrett & Charles Grisham • University of Virginia

Chapter 8Lipids

Outline• What are the structures and chemistry of fatty acids?• What are the structures and chemistry of triacylglycerols? • What are the structures and chemistry of

glycerophospholipids?• What are sphingolipids, and how are they important for

higher animals? • What are waxes, and how are they used?• What are terpenes, and what is their relevance to

biological systems?• What are steroids, and what are their cellular functions?• How do lipids and their metabolites act as biological

signals?• What can lipidomics tell us about cell, tissue, and organ

physiology?

Classes of Lipids

All biological lipids are amphipathic

• Fatty acids • Triacylglycerols • Glycerophospholipids • Sphingolipids • Waxes • Isoprene-based lipids (including steroids)

8.1 What Are the Structures and Chemistry of Fatty acids?

8.1 What Are the Structures and Chemistry of Fatty acids?

•Fatty acids are comprised of alkyl chains terminated by carboxylic acid groups.

•Shown here is palmitic acid, a 16-carbon saturated fatty acid.

•The term “saturated” indicates that the acyl chain is fully reduced, i.e., saturated with hydrogens and electrons.

8.1 What Are the Structures and Chemistry of Fatty acids?

Structural consequences of unsaturation

• Saturated chains pack tightly and form more rigid, organized aggregates (i.e., membranes)

• Unsaturated chains bend and pack in a less ordered way, with greater potential for motion

Fats in the human diet vary widely in their composition

Diets high in trans fatty acids raise plasma LDL cholesterol levels Trans fatty acids are present at low levels in dairy and meat products from ruminant animals. “Partially hydrogenated” fats in foods contain much higher amounts.

8.2 What Are the Structures and Chemistry of Triacylglycerols?

Triacylglycerols are also called triglycerides • They are a major energy source for many

organisms • Why?

• Most reduced form of carbon in nature• No solvation needed • Efficient packing

8.2 What Are the Structures and Chemistry of Triacylglycerols?

Most of the fatty acids in plants and animals exist in the form of triacylglycerols. If all three fatty acids are the same, the molecule is called a simple triacylglycerol.

8.2 What Are the Structures and Chemistry of Triacylglycerols?

Mixed triacylglycerols contain two or three different fatty acids.

Polar Bears Prefer Nonpolar Food

Polar bears face an ironic dilemma. They are surrounded by water they cannot use. Ice and snow are too cold and seawater is too salty. They produce all the water they need from metabolism of fat: (CH2) + 1.5O2 → CO2 + H2O

Interestingly, adult polar bears consume only fat (from seals they catch). By not consuming protein (and merely recycling their own proteins into new ones), they have no need to urinate or defecate and go for months without doing so, thus saving precious body water.

8.3 What Are the Structures and Chemistry of Glycerophospholipids

Glycerophospholipids are essential components of cell membranes and are also found in other parts of cells.

8.3 What Are the Structures and Chemistry of Glycerophospholipids

The structure of phosphatidylcholine.

8.3 What Are the Structures and Chemistry of Glycerophospholipids

Phosphatidyl-β-D-glucopyranoside• Phosphatidyl-β-D-glucopyranoside is a

glycophospholipid• Identified in several cell types, it plays a role in

formation of plasma membrane signaling microdomains involved in cellular differentiation and maturation.

Ether Glycerophospholipids Include PAF and Plasmalogens

Ether glycerophospholipids possess an ether linkage instead of an acyl group at the C-1 position of glycerol.

•Plasmalogens are ether glycerophospholipids in which the alkyl chain is unsaturated

Ether Glycerophospholipids Include PAF and Plasmalogens

8.4 What Are Sphingolipids and How Are They Important for Higher Animals?

• Sphingolipids represent another class of lipids found frequently in biological membranes

• Sphingosine, an 18-carbon alcohol, forms the backbone of these lipids rather than glycerol

• A fatty acid joined to sphingosine in amide linkage forms a ceramide

• Glycosphingolipids are ceramides with one or more sugars in beta-glycosidic linkage at the 1-hydroxyl group

8.4 What Are Sphingolipids and How Are They Important for Higher Animals?

• Glycosphingolipids with one sugar are cerebrosides

• Ceramides with 3 or more sugars, one of which is a sialic acid, are gangliosides

8.4 What Are Sphingolipids and How Are They Important for Higher Animals?

Sphingolipids are based on the structure of sphingosine.

Sphingosine is an 18-carbon alcohol. Fatty acids joined in amide linkage at the highlighted nitrogen form ceramides.

8.4 What Are Sphingolipids and How Are They Important for Higher Animals?

Figure 8.10 A ceramide is formed by joining a fatty acid in amide linkage to a sphingosine.

8.4 What Are Sphingolipids and How Are They Important for Higher Animals?

A ceramide with a phosphocholine head group is a choline sphingomyelin.

8.4 What Are Sphingolipids and How Are They Important for Higher Animals?

Gangliosides are important components of muscle and nerve membranes.

8.5 What Are Waxes, and How Are They Used?

Waxes are esters of long-chain alcohols with long-chain fatty acids

• Waxes are insoluble in water, due to their mostly hydrocarbon composition

• Animal skin and fur are wax-coated and are water-repellent

• Leaves of many plants and bird feathers are similarly water-repellent

• Carnauba wax, from a palm tree in Brazil, is a hard wax used for high-gloss finishes for automobiles, boats, floors, and shoes

• Lanolin is a wool wax used in cosmetics; Oil of Olay is named for its lanolin content

8.5 What Are Waxes, and How Are They Used?

Waxes consist of long-chain alcohols esterified to long-chain fatty acids. Triacontanol palmitate is the principal component of beeswax.

8.6 What Are Terpenes, and What is Their Relevance to Biological Systems?

Terpenes are a class of lipids formed from combinations of isoprene units

• “Isoprene” is 2-methyl-1,3-butadiene• Monoterpenes consist of two isoprene units• Sesquiterpenes consist of three isoprenes• A diterpene consists of four isoprene units• All steroids (including cholesterol and the

steroid hormones) are terpene-based molecules

8.6 What Are Terpenes, and What is Their Relevance to Biological Systems?

•Note the two possible linkage modes:•“head-to-tail”•“tail-to-tail”

The structure of isoprene (2-methyl-1,3-butadiene) and the structure of head-to-tail and tail-to-tail linkages. Isoprene itself can be formed by distillation of natural rubber, a linear head-to-tail polymer of isoprene units.

8.6 What Are Terpenes, and What is Their Relevance to Biological Systems?

Many monoterpenes are readily recognized by their characteristic flavors or odors (limonene in lemons; citronellal in roses and perfumes; menthol used in cough drops).

8.6 What Are Terpenes, and What is Their Relevance to Biological Systems?

The diterpenes include retinal (the visual pigment in rhodopsin), and phytol (found in chlorophyll. Gibberellic acid is a plant hormone.

8.6 What Are Terpenes, and What is Their Relevance to Biological Systems?

The triterpene lanosterol is a constituent of wool fat and is also a precursor to cholesterol and the other steroids. Lycopene is a carotenoid found in ripe fruit, especially tomatoes.

8.7 What Are Steroids, and What Are Their Cellular Functions?

• Steroids are polyprenyl (isoprene-based) molecules built on a core structure of three 6-membered rings and one 5-membered ring, all fused together

• Cholesterol is the most common steroid in animals and precursor for all other steroids in animals

• Steroid hormones serve many functions in animals - including salt balance, metabolic function and sexual function

8.7 What Are Steroids, and What Are Their Cellular Functions?

The structure of cholesterol, shown with steroid ring designations and carbon numbering.

8.7 What Are Steroids, and What Are Their Cellular Functions?

Cortisol provides control of carbohydrate, protein, and lipid metabolismTestosterone is the primary male sex steroid hormoneEstradiol is the primary female sex steroid hormoneProgesterone is a precursor of testosterone and estradiol

8.8 How Do Lipids and Their Metabolites Act as Biological Signals?• Glycerophospholipids and sphingolipids play

important roles as chemical signals in and on cells• Lipid signals act locally, either within the cell where

they are made or on nearby cells• These signals typically initiate a cascade of reactions

with multiple effects• The lifetimes of these signals are usually very short• The creation and breakdown of lipid signals is

carefully regulated and timed• Some of the reactions that produce these signals are

shown on the next slide

8.8 How Do Lipids and Their Metabolites Act as Biological Signals?

Phospholipases A1 and A2 cleave fatty acids from a glycerophospholipid, producing lysophospholipids. Phospholipases C and D hydrolyze on either side of the phosphate in the polar head group.

8.9 What Can Lipidomics Tell Us about Cell, Tissue, and Organ Physiology?• Many human diseases involve the disruption of lipid

metabolic enzymes and pathways.• New techniques have made possible the global

analysis of lipids and their interacting protein partners in organs, cells, and organelles – an approach termed lipidomics

• Typical cells contain over a thousand different lipids• Complete understanding of lipid function will require

the determination of which lipids are present and in what concentrations

• Cellular lipidomics provides a framework for understanding the myriad roles of lipids

End of Chapter Problems• All problems can be done.