Structure and Physiological Significance of Lipids脂类的结构和功能

Deqiao Sheng PhD

Biochemistry Department

Definition Classes （分类）

Function （功能）

Lipids脂类

Fats : triacylglycerols(TG) 甘油三酯脂肪 cholesterol, Ch 胆固醇

cholesteryl ester, CE 胆固醇

phospholipids, PL 磷脂glucolipids, GL 糖脂

Summary

Lipoids类脂

Lipids 脂类 , protein 蛋白质 and carbohydrates 碳水化合物

Like proteins and carbohydrates, lipids are essential components （组分） of all living organisms.

Unlike proteins and carbohydrates, however, lipids have widely varied structures.

They are often defined as water-insoluble （水溶性） organic compounds found in biological systems. Lipids have high solubility in nonpolar organic solvents （非极性有机溶剂） .

Definition

Lipids are non-polar (hydrophobic 疏水的 ) compounds which can be soluble in organic solvents.

Lipids have a variety of biological roles: they serve as fuel molecules, highly concentrated energy stores, signal molecules, and components of membranes.

The biological functions of lipids are diverse

1. Certain lipids (e.g., triacylglycerols) serve as efficient reserves for the storage of energy. ----Storage lipids 储存脂

2. Lipids (including mainly glycerophospholipids, sphingolipids, and sterols) are the major structural elements of the biomembranes.

----Membrane lipids 膜脂

3. The water-insoluble vitamins( 维生素 ) like vitamin A, D, E, K and some hormones (like steroids （类脂） , prostaglandins（前列腺素） ) are lipids.

4. Lipids also serve as enzyme cofactors, light-absorbing pigments, intracellular messengers.

Biological membranes contain a variety of amphipathic lipids, including glycerophos-pholipids and sphingolipids.

In some organisms, triacylglycerols (fats and oils) function as intracellular storage molecules for metabolic energy.

Lipids have diverse biological functions as well as diverse structures

Fats also provide animals with thermal insulation and padding.

Waxes in cell walls, exoskeletons, and skins protect the surfaces of some organisms. Some lipids have highly specialized functions.

Lipids Functions

1. Excellent energy reserves

2. Structure of cell membranes

3. Organ padding

4. Body thermal insulation

5. Essential fatty acids (EFA)

6. Hormone synthesis

7. Fat soluble vitamin absorption

Lipids Disorder

Lipids deficiency (Shortage in Lipids intake)

Lipids exceeding (Overtaking in Lipids intake)

Lipids Deficiency

Fat should comprise of 3% of total calories to prevent fatty acid deficiency

Fatty acid deficiency syndromes– Dry scaly skin, dermatitis ( 皮炎， Linoleic

acid deficiency)

– Hand tremors (Prostaglandin deficiency)

– Inability to control blood pressure

Lipids Exceeding

Fat should comprise not more than 30% of total calories to prevent lipids exceeding.

To prevent overtaking, we should consume fat breakdown (% total calories)– <8% from saturated fat– 10% from polyunsaturated fat– 10-15% from monounsaturated fat

Health Problems Energy Intake > Energy needed =

Lipids overtaking Develop medical problem

– Cancer– Heart disease– Diabetes– Obesity– High blood pressure– High blood cholesterol

Lipids are classified as simple or complex

1. Simple lipids: Esters of fatty acids with various alcohols.

a. Fats: Esters of fatty acids with glycerol. Oils are fats in the liquid state.

b. Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols.

2. Complex lipids: Esters of fatty acids containing groups in addition to an alcohol and a fatty acid.

a. Phospholipids: Lipids containing, in addition to fatty acids and an alcohol, a phosphoric acid residue. They frequently have nitrogen containing bases and other substituents.

b. Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine, and carbohydrate.

c. Other complex lipids: Lipids such as sulfolipids and aminolipids. Lipoproteins may also be placed in this category.

3. Precursor and derived lipids: These include fatty acids, glycerol, steroids, other alcohols, fatty aldehydes, and ketone bodies, hydrocarbons, lipid-soluble vitamins, and hormones.

Fatty acids Are Key Constituents of Lipids

Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end.

Fatty acids occur mainly as esters in natural fats and oils but do occur in the unesterified form as free fatty acids （ FFA ） , a transport form found in the plasma.

The chain may be saturated (containing no double bonds) or unsaturated (containing one or more double bonds).

Fatty acids also play important roles in signal-transduction pathways

A fatty acid is composed of a long hydrocarbon chain (“tail”) and a terminal carboxyl group (or “head”).

16:0 palmitic acid软脂酸；十六碳酸

Fatty acids (even number of carbon atoms） Saturated fatty acids

palmitic acid 16C stearic acid 18C

Unsaturated fatty acids Linolenic acid 18C three unsaturated bonds Linoleate 18C two unsaturated bonds Arachidonic acid 20C four unsaturated bonds

Essential fatty acids Required for the growth of mammals and they must

be obtained from food. Including linoleate （亚油酸）、linolenate （ 亚 麻 酸 ） , arachidonic acid （ 花 生 四 烯

酸） amount unsaturated in plant

Nomenclature

The packing of fatty acids into stable aggregates

The Naming of Fatty Acids

Fatty acids can be referred to by either International Union of Pure and Applied Chemistry (IUPAC) names or common names.

Fatty acids are hydrocarbon chains of various lengths and degrees of unsaturation that terminate with carboxylic acid groups.

The number of carbon atoms in the most abundant fatty acids ranges from 14 to 24 and is almost always even since fatty acids are synthesized by the sequential addition of two-carbon units. In IUPAC nomenclature, the carboxyl carbon is labeled

C-1 and the remaining carbon atoms are numbered sequentially.

In common nomenclature, Greek letters are used to identify the carbon atoms. The carbon adjacent to the carboxyl carbon (C-2 in IUPAC nomenclature) is designated , and the other carbons are lettered , , , and so on .

The configuration of the double bonds in unsaturated fatty acids is generally cis. In IUPAC nomenclature, the positions of double bonds are indicated by the symbol where the superscript Δn indicates the lower-numbered carbon atom of each double-bonded pair.

The notation 18:0 denotes a fatty acid with no double 18 bonds, whereas 18:2 signifies that there are two double bonds.

A shorthand notation for identifying fatty acids uses two numbers separated by a colon; the first refers to the number of carbon atoms in the fatty acid, and the second refers to the number of carbon–carbon double bonds, with their positions indicated as superscripts following a Greek symbol, Δ .

In this notation, palmitate is written as 16:0, oleate as 18:1 Δ9 and arachidonate as 20:4 Δ5,8,11,14 .

There is free rotation about C-C bonds in the fatty acid hydrocarbon, except where there is a double bond.

Each cis double bond causes a kink in the chain.

Rotation about other C-C bonds would permit a more linear structure than shown, but there would be a kink.

C

O

O 1

23

4

fatty acid with a cis-9 double bond

Some fatty acids and their common names:14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid; 18:1 cis9  oleic acid( 油酸 )

18:2 cis9,12  linoleic acid( 亚油酸 )18:3 cis9,12,15  -linonenic acid （亚麻酸）20:4 cis5,8,11,14  arachidonic acid( 花生四烯酸 )20:5 cis5,8,11,14,17  eicosapentaenoic acid ( 二十碳五烯酸 , an omega-3)

Various conventions Δ use for indicating the number and position of the double bonds ; eg Δ9 indicates a double bond between carbons 9 and 10 of the fatty acid;

Some naturally occurring fatty acids in animals

ω9 indicates a double bond on the ninth carbon counting from the ω- carbon. In animals additional double bonds are introduced only between the existing double bond (eg, ω9, ω6, or ω3) and the carboxyl carbon, leading to three series of fatty acids known as the ω9, ω6, and ω3 families, respectively.

Essential Fatty Acids

Omega-3 (ω-3) and omega-6 (ω-6) fatty acids are unsaturated “Essential Fatty Acids” . The two EFAs are linolenic (ω-3) and linoleic (ω-6). The “3” and “6” indicate where the first double bond occurs in the fatty acid molecule.

Example: DHA (docosahexenoic acid, C22:6, 廿二碳六烯酸 ) and AA (arachidonic acid, C20:4, 花生四烯酸 ) are both crucial to the optimal development of the brain and eyes.

Fatty Acids Vary in Chain Length and Degree of Unsaturation

Fatty acids in biological systems usually contain an even number of carbon atoms, typically between 14 and 24 . The 16- and 18-carbon fatty acids are most common.

The properties of fatty acids and of lipids derived from them are markedly dependent on chain length and degree of saturation. Unsaturated fatty acids have lower melting points than saturated fatty acids of the same length.

Fatty acids that do not contain any carbon–carbon double bonds are classified as saturated, whereas those with at least one carbon–carbon double bond are classified as unsaturated.

Unsaturated fatty acids with only one carbon–carbon double bond are called monounsaturated, and those with two or more are called polyunsaturated.

The configuration of the double bonds in unsaturated fatty acids is generally cis.

Chemical structures of three C18 fatty acids. (a) Stearate (octadecanoate), a saturated fatty acid. (b) Oleate (cis- Δ9 –octadecenoate), a monounsaturated fatty acid. (c) Linolenate (all-cis- Δ9,12,15 –octadecatrienoate), a polyunsaturated fatty acid.

Triacylglycerols Are the Main Storage Forms of Fatty acids

Fatty acids are generally stored as neutral lipids called triacylglycerols.

The triacylglycerols are esters of the trihydric alcohol glycerol and fatty acids.

Mono- and di-acylglycerols wherein one or two fatty acids are esterified with glycerol are also found in the tissues. These are of particular significance in the synthesis and hydrolysis of triacylglycerols.

Triacylglycerols are composed of three fatty acids each in ester linkage with a single glycerol.

Triacylglycerol (TG)

Most lipids in the average human diet are triacylglycerols. These lipids are broken down in the small intestine by the action of lipases (pancreas).

Pancreatic lipase catalyzes hydrolysis of the primary esters (at C-1 and C-3) of triacylglycerols, releasing fatty acids and generating monoacyl-glycerols.

In mammals, most fat is stored in adipose tissue, which is composed of specialized cells known as adipocytes. Each adipocyte contains a large fat droplet that accounts for nearly the entire volume of the cell .

Adipose tissueLarge adipocytes (brown) are filled with fat droplets. They are embedded in collagen matrix. Most cells are close to capillaies (red).

Triacylglycerols Provide Stored Energy and Insulation

In most eukaryotic cells, triacylglycerols form a separate phase of microscopic, oily droplets in the aqueous cytosol, serving as depots of metabolic fuel.

In vertebrates, specialized cells called adipocytes, or fat cells, store large amounts of triacylglycerols as fat droplets that nearly fill the cell .

Humans have fat tissue (composed primarily of adipocytes) under the skin, in the abdominal cavity, and in the mammary glands.

Moderately obese people with 15 to 20 kg of triacylglycerols deposited in their adipocytes could meet their energy needs for months by drawing on their fat stores.

In some animals, triacylglycerols stored under the skin serve not only as energy stores but as insulation against low temperatures. Seals, walruses, penguins, and other warm-blooded polar animals are amply padded with triacylglycerols. In hibernating animals (bears, for example), the huge fat reserves accumulated before hibernation serve the dual purposes of insulation and energy storage .

Many Foods Contain Triacylglycerols

Most natural fats, such as those in vegetable oils, dairy products, and animal fat, are complex mixtures of simple and mixed triacylglycerols.

Phospholipids Are the Major Class of Membrane Lipids

Sphingosine

There Are Three Common Types of Membrane Lipids

Phospholipids may be regarded as derivatives of phosphatidic acid, in which the phosphate is esterified with the -OH of a suitable alcohol.

Glycerophospholipids

Two fatty acids are attached in ester linkage to the first and second carbons of glycerol, and a highly polar or charged group is attached through a phosphodiester linkage to the third carbon.

胆碱

乙醇胺

Structure of Phospholipid

Phosphatidylcholines (Lecithins, 卵磷脂 ) Occur in Cell Membranes

Phosphoacylglycerols containing choline are the most abundant phospholipids of the cell membrane and represent a large proportion of the body’s store of choline.

Choline is important in nervous transmission, as acetylcholine( 乙酰胆碱 ), and as a store of labile methyl groups.

Sphingolipids

After glycerophospholipids, the most abundant lipids in plant and animal membranes are sphingolipids( 神经鞘脂类 ).

Sphingolipids are derivatives of sphingosine. In mammals, sphingolipids are particularly

abundant in tissues of the central nervous system.

Sphingolipids

Glycolipids Are Important In Nerve Tissues & In The Cell Me

mberane

Glycolipids, as their name implies, are sugar-containing lipids.

Glycolipids are widely distributed in every tissue of the body, particularly in nervous tissue such as brain.

They occur particularly in the outer leaflet of the plasma membrane, where they contribute to cell surface carbohydrates.

Sphingolipids

The major glycolipids found in animal tissues are glycosphingolipids. They contain ceramide and one or more sugars.

Structure of galactosylceramide (galactocerebroside, R = H), and sulfogalactosylceramide (a sulfatide, R = SO4

2- )

In sphingomyelins, phosphocholine is attached to the C-1 hydroxyl group of a Ceramide.

Cerebrosides are glycosphingolipids that contain one monosaccharide residue attached by a linkage to C-1 of a ceramide.

Gangliosides are more complex glycosphingolipids in which oligosaccharide chains containing N-acetylneuraminic acid (NeuNAc) are attached to a ceramide.

Sphingolipids

Steroids Play Many Physiologically Important Roles

Cholesterol ( 胆固醇 ) is a lipid with a structure quite different from that of phospholipids. It is a steroid ( 类固醇 ), built from four linked hydrocarbon rings.

Cholesterol, the major sterol in animal tissues, is amphipathic, with a polar head group (the hydroxyl group at C-3) and a nonpolar hydrocarbon body.

The steroid nucleus

Cholesterol

Steroids contain four fused rings: three six-carbon rings designated A, B, and C and a five-carbon D ring.

Plant and animal food contain sterols ( 固醇 ) but only animal food contain cholesterol( 胆固醇 ). Cholesterol is needed to make bile, sex ho

rmones, steroids and vitamin D. Sources – egg yolks, liver, shellfish, organ foo

ds

Cholesterol Is a Significant Constituent of Many Tissues

Cholesterol is widely distributed in all cells of the body but particularly in nervous tissue.

It is a major constituent of the plasma membrane and of plasma lipoproteins.

Cholesterol often accumulates in lipid deposits (plaques) on the walls of blood vessels. These plaques have been implicated in cardiovascular disease, which can precipitate heart attacks or strokes.

Many people limit their intake of cholesterol!

Despite its implication in cardiovascular disease, cholesterol plays an essential role in mammalian biochemistry.

Cholesterol is synthesized by mammalian cells. It is not only a component of certain membranes but also an essential precursor of steroid hormones and bile salts.

Vitamin D3 production and metabolism.

(a) Cholecalciferol (vitamin D3) is produced in the skin by UV irradiation of 7-dehydrocholesterol, which breaks the bond shaded pink. In the liver, a hydroxyl group is added at C-25 (pink); in the kidney, a second hydroxylation at C-1 (pink) produces the active hormone, 1,25-dihydroxycholecalciferol. This hormone regulates the metabolism of calcium (Ca2+) in kidney, intestine, and bone.

(b) Dietary vitamin D prevents rickets( 软骨病 ), a disease once common in cold climates where heavy clothing blocks the UV component of sunlight necessary for the production of vitamin D3 in skin. On the left is a 2 1/2-year-old boy with severe rickets; on the right, the same boy at age 5, after 14 months of vitamin D therapy.

Biological Membranes Are Composed of Lipid Bilayers and Proteins

Biological membranes define the external boundaries of cells and separate compartments within cells. They are essential components of all living cells.

A typical membrane consists of two layers of lipid molecules and many embedded proteins.

Membrane lipid and bilayer.

(a) An amphipathic membrane lipid.

(b) Cross-section of a lipid bilayer. The hydrophilic head groups (blue) of each leaflet face the aqueous medium, and the hydrophobic tails (yellow) pack together in the interior of the bilayer.

Structure of a typical eukaryotic plasma membrane.

A lipid bilayer forms the basic matrix of biological membranes, and proteins (some of which are glycoproteins) are associated with it in various ways. The oligosaccharides of glycoproteins and glycolipids are on the exterior surface of the membrane.

Some proteins contained in membranes serve as selective pumps that strictly control the transport of ions and small molecules into and out of the cell.

Membranes are also responsible for generating and maintaining the proton concentration gradients essential for the production of ATP.

Receptors in membranes recognize extracellular signals and communicate them to the cell interior.

Biological membranes have a wide variety of complex functions

SUMMARY

1. Lipids have the common property of being relatively insoluble in water (hydrophobic) but soluble in nonpolar solvents. Amphipathic lipids also contain one or more polar groups, making them suitable as constituents of membranes at lipid:water interfaces.

2. The lipids of major physiologic significance are fatty acids and their esters, together with cholesterol and other steroids.

3. Long-chain fatty acids may be saturated, monounsaturated, or polyunsaturated, according to the number of double bonds present. Their fluidity decreases with chain length and increases according to degree of unsaturation.

4. The esters of glycerol are quantitatively the most significant lipids, represented by triacylglycerol (“fat”), a major constituent of lipoproteins and the storage form of lipid in adipose tissue.

5. Glycolipids are also important constituents of nervous tissue such as brain and the outer leaflet of the cell membrane, where they contribute to the carbohydrates on the cell surface.

6. Cholesterol, an amphipathic lipid, is an important component of membranes. It is the parent molecule from which all other steroids in the body, including major hormones such as the adrenocortical and sex hormones, D Vitamins, and bile acids, are synthesized.