L15 Carbohydrates

一、Carbohydrate Functions

Carbohydrates have numerous functions in biochemistry:

1. generating and storing biological energy
2. molecular recognition (as in the immune system)
3. cellular protection (as in bacterial and plant cell walls)
4. cell signaling
5. cell adhesion
6. biological lubricants
7. controlling protein trafficking
8. maintaining biological structure (e.g., cellulose)

二、Representative Carbohydrates

Strictly speaking, the term carbohydrate is reserved for compounds with the $(CH_{2}O)_{n}$ empirical formula, while the term saccharide covers both these compounds and all derivatives of carbohydrates

The three compounds shown here are composed entirely of C, H, and O, with glucose forming the monomer for the oligomer and the polymer.

The carbohydrate is ：
$$
(CH_{2} O)_{n}, n = 3 \text{ ~ } 7
$$

1. Tautomers 互变异构体

互变异构是某些有机化合物的结构在两种官能团异构体间产生平衡互相转换的现象，相应的异构体则称为互变异构体。

大多数互变异构都涉及氢原子或质子的转移，以及单键向双键的转变。互变异构体在平衡中的分布与具体的因素有关，包括温度、溶剂和pH值等。

2. Enantiomers 对映异构体

映射异构体（英语：Enantiomer），又称对掌异构物、光学异构物、镜像异构物或对映异构体，不能与彼此立体异构体镜像完全重叠。

互为镜像（mirror images）的分子。不对称碳原子和四种不同的原子或原子基团连结，不对称碳为手性中心。当有n个手性中心时，则最多有2的n次方立体异构物。

3. Diastereomer 非对映异构体

非对映异构（英文：Diastereomerism）是指属于立体异构但不属于对映异构的所有同分异构现象，所涉及的异构体称为非对映异构体，简称非对映体。

它们包括顺反异构体、构象异构体、内消旋化合物和具有非对映关系的光学异构体。

狭义地讲，非对映异构体仅包含具有一个或多个手性中心但不互为镜像关系的化合物。

非对映异构体以赤式（erythro）和苏式（threo）标记。赤式异构体是两个相同取代基在费歇尔投影式中处于同侧的异构体，苏式则相反。

Monosaccharides 单糖

The simplest carbohydrates are small, monomeric molecules—the monosaccharides, typically containing from three to nine carbon atoms, which include simple sugars such as glucose

The smallest molecules usually regarded as monosaccharides are the trioses, with n = 3.

The suffix ose is commonly used to designate compounds as saccharides.) Monosaccharides are generally characterizedby the presence of one carbonyl group (aldehyde or ketone) and one or more hydroxyl groups.

The Carbonyl Group 羰基 ### 1. Tautomers 互变异构体

Trioses（丙糖） are the simplest monosaccharides.

The two triose tautomers illustrate the difference between aldose and ketose monosaccharides, also called more descriptively aldotriose and ketotriose, respectively

Carbon numbering begins in all aldoses with the aldehyde carbon and in ketoses with the end carbon closest to the ketone group

The enediol intermediate through which they are interconverted is unstable and cannot be isolated.

2. Enantiomers 对映异构

Enantiomers, which are nonsuperimposable mirror images of one another.

The most compact way to represent enantiomers is to use a Fischer projection.

In a Fischer projection the bonds that are drawn horizontally are imagined as coming toward you; those drawn vertically are receding

D and L forms of a monosaccharide are nonsuperimposable mirror images and are called enantiomers.

Monosaccharide Enantiomers in Nature

The most important naturally occurring saccharides are the D enantiomers.

Just as in the case of amino acids, one enantiomeric form of monosaccharides dominates in living organisms. In proteins it is the L-amino acids; in carbohydrates it is the D-monosaccharides.

Once fixed in the early evolution, then it persisted.

Alternative Designations for Enantiomers: D–L and R–S

(1) D-L

Originally, the terms D and L were meant to indicate the direction of rotation of the plane of polarization of polarized light: D for right (dextro), L for left (levo).

(2) R-S

R-S nomenclature. The R-S system describes absolute stereochemical configuration, as shown in this example.

Each type of group attached to a chiral carbon (gray) is given a priority, according to a set of defined rules.

Priorities for groups common in carbohy-drate chemistry are SH > OR > OH > NH2 > CO2H > CHO > CH2OH > CH3 >H.

We view the molecule with the group of lowest priority away from us (H in our example).

• If the priority of the remaining three groups decreases clockwise, the absolute configuration is called R (from Latin rectus, “right”).
• If priority decreases coun-terclockwise, the configuration is S (from Latin sinister, “left”).
• In this notation, D-glyceraldehyde is R-glyceraldehyde, and L-glyceraldehyde is S-glyceraldehyde.

The enantiomers of glyceraldehyde

The configuration of groups around the chiral carbon 2 distinguishes D-glyceraldehyde from L-glyceraldehyde.

The two molecules are mirror images and cannot be superimposed on one another.

3. Diastereomer 非对映异构

When we consider monosaccharides with more than three carbons, a further structural complication appears. Such a monosaccharide may have more than one chiral carbon, which results in its having two types of stereoisomers.

These types are enantiomers (mirror image isomers), which we have already discussed, and diastereomers which we first encounter in the tetrose monosaccharides.

Stereochemistry of aldotetroses（醛糖苷）(Tetrose Diastereomers)

These molecules have two chiral carbons and thus have two diastereomeric forms, threose and erythrose, each with a pair of enantiomers.

When monosaccharides contain more than one chiral carbon, the prefix D or L designates the configuration about the carbon farthest from the carbonyl group.

Isomers differing in orientation about other carbons are called diastereomers and given different names.

Diastereomer: 2 and 3; 1 and 4 Enantinomers: 1 and 2; 3 and 4 In general, a molecule with *n* chiral centers will have $2^{n}$ stereoisomers because there are two possibilities at each chiral center.

The prefix D or L is used to designate the orientation about the chiral carbon farthest from the carbonyl group carbon - number 3 in this case.

Thus, threose and erythrose are two aldotetroses with opposite orientations about carbon 2. Stereoisomers of this kind, which are not mirror images, are called diastereomers.

苏糖（英语：Threose，C4H8O4）在分类上属于丁糖与醛糖，从费希尔式的角度看，中间两个碳原子上的羟基在碳骨架的两侧。

赤藓糖（英语：Erythrose）在分类上属于丁糖与醛糖，在费希尔式看来，中间两个碳原子上的羟基在碳骨架的同侧。其衍生物赤藓糖-4-磷酸是磷酸戊糖途径非氧化反应阶段中的一种中间代谢物。

Often the ketose name is derived from the corresponding aldose name by insertion of the letters ul. Thus erythrose becomes erythrulose.

4. Aldoses（醛糖） and Ketoses（酮糖）

There are two trioses: glyceraldehyde（甘油醛） and dihydroxyacetone（二羟丙酮）（Figure 9.3）

Glyceraldehyde is an aldehyde, one of a class of monosaccharides called aldoses. Dihydroxyacetone is a ketone; such monosaccharides are called ketoses.

Figure 9.3 Note that glyceraldehyde and dihydroxyacetone each have one carbonyl carbon and both have the same atomic composition

They are tautomers (structural isomers differing in location of hydrogen atoms and double bonds) and can interconvert via an unstable enediol (烯二醇) intermediate（Figure 9.3）

Such tautomeric interconversions occur to a certain extent between all such pairs of aldose and ketose monosaccharides, but the reactions are usually very slow unless catalyzed. Thus, glyceraldehyde and dihydroxyacetone can each exist as a stable compound.

(1) Stereochemical relationships of the D-aldoses（D-醛糖）

醛糖（英语：Aldose） 是一类单糖，每个分子含有一个醛基，化学式的规律为$C_{n}H_{2n}O_{n}$（n>=3）。

Figure 9.8(a) ##### (2) Stereochemical relationships of the D-ketoses（D-酮糖）

酮糖（英语：Ketose）是一种单糖，每一个糖分子含有一个酮基。类单糖，该单糖中氧化数最高的C原子（指定为C-2）是一个酮基。

Figure 9.8(b) #### Aldose Ring Structures 醛糖环结构

Having five or six carbons in the chain gives these compounds the potential to form very stable ring structures via internal hemiacetal (半缩醛) formation.

半缩醛（Hemiacetal）是一类同一碳上连有一个羟基，一个烷氧基和一个氢的有机化合物。半缩醛可由醛与醇反应得到，而半缩醛可以继续和醇反应得到缩醛。

半缩醛在酸性和碱性水溶液中都是不稳定的。

The bond angles characteristic of carbon and oxygen bonding are such that ringscontaining fewer than five atoms are strained to a considerable extent, whereas five-or six-membered rings are easily formed.

(1) 相关异构体

端基差向异构 Anomer

端基差向异构又称为首旋异构物，一般存在于糖类中，是差向异构的一种，两个非对映异构体分子（异头物）的差异在于糖类环形结构半缩醛/半缩酮碳原子（异头碳）的构型不同。

1号碳的羟基若与5号碳的羟甲基处于哈沃斯透视式平面的两侧，则定义为α-异构体，反之称为β-异构体。吡喃葡萄糖的两种端基差向异构体可分别称为“α-D-吡喃葡萄糖”和“β-D-吡喃葡萄糖”。

α-异构体与β-异构体的互相转化称为变旋现象。α-异构体受端基异构效应影响而得到稳定。

Monosaccharides with five or more carbons exist preferentially in five- or six-membered ring structures (Haworth projections), resulting from internal hemiacetal formation.

Two anomeric forms (not exisit in linear structures), and are possible, α and β

杂环化提供了一个额外的手性分子 (Cyclization has created a new asymmetric center at carbon 1.)

Figure 9.9 That is why we have had to draw two stereoisomers of D-ribofuranose in Figure 9.9, referred to as α-D-ribofuranose and β-D-ribofuranose, as well as a corresponding pair of ribopyranoses.

Like other kinds of stereoisomers, these and forms rotate the plane of polarized light differently and can be distinguished in that way.

Such isomers, differing in configuration only at the carbonyl carbon (C1 in this case), are called anomers, and carbon 1 is often referred to as the anomeric carbon atom.

The monosaccharides can undergo interconversion between the α and β forms, using the open-chain structure as an intermediate. This process is referred to as mutarotation（变旋）.

Enzymes called mutarotases catalyze this process in vivo.

构象异构 Conformational isomers And 构型异构 Configuration isomers

The different ring conformations produced by slightly different bond angles are called conformational isomers

These models show two of the possible ring conformations for β-D-ribofuranose.

In both of them, C-1, O, and C-4 define a plane.

In the C-2 endo conformation (a), C-2 is above the plane.

In the C-3 endo conformation (b), C-3 is above the plane.

These isomers are the two most common conformations for ribose and deoxyribose in nucleic acids.

A C-3 exo conformation would look like the figure in (b), but C-3 would be flipped below the plane.

Boat And Chair Conformations

• For most sugars, the chair form is more stable because substituents on axial bonds tend to be more crowded in the boat form.

Conformation and configuration are different.

• Conformational isomers can interchange by a simple deformation of the molecule
• Configurational isomers, such as the various kinds of stereoisomers described earlier, can interconvert only through the breaking and re-formation of covalent bonds.

Glucose and mannose differ from each other only in the configuration about C2. Sugars of this type, differing in configuration about only one carbon, are called epimers.

In stereochemistry, epimer refers to one of a pair of stereoisomers. The two isomers differ in configuration at only one stereogenic center. All other stereocenters in the molecules, if any, are the same in each.

特定构型的决定（特定条件下不同异构体之间的比例分配）

Under physiological conditions in solution, monosaccharides with five or more carbons exist typically more than 99% in the ring forms. （正常生理条件下，大部分单糖都处于环状形态）

The distribution between pyranose and furanose forms depends on:

• the particular sugar structure
• the pH
• the solvent composition
• the temperature

由于以上的因素会影响在特定条件下某种糖环的构型，因此在特定的生理条件下，特定的结构is favored

For example, as Table 9.2 shows, D-ribose exists in solution as a mixture of the two ring forms. But in biological compounds, specific forms are stabilized.

(2) Pentose Rings

Reaction of the C-1 of D-ribose with the C-4 hydroxyl produces a five-membered ring structure called a furanose (呋喃糖); the name reflects its structural similarity to the heterocyclic (杂环的) compound furan (呋喃)

呋喃（英语：furan）是一种含有一个由四个碳原子和一个氧原子的五元芳环的杂环有机物。含有这样的环的化合物通常是呋喃的同系物。

Furan's Structure > 呋喃糖(英文：Furanose)是一种糖，用于总称碳水化合物所具有的化学结构，其中包含一个由四个碳原子和1个氧原子所组成的五元环状结构。呋喃糖是呋喃的衍生物，但是呋喃糖环没有双键。

(3) Hexose Rings

A six-membered ring is obtained if the reaction occurs with the C-5 hydroxyl. Such a six-membered ring is called a pyranose (吡喃糖), to indicate its relation to the heterocyclic compound **pyran **(吡喃)

吡喃（Pyran）是含有一个氧原子的完全不饱和六元杂环化合物。它有两个双键，根据双键位置的不同，可以有两个异构体：2H-吡喃和4H-吡喃。

吡喃糖(英语：Pyranose)是一种糖，用于总称碳水化合物所具有的化学结构，其中包含一个由5个碳原子和1个氧原子所组成的六元环状结构。可能会有其他的碳原子在环以外。吡喃糖是吡喃的衍生物，但是吡喃糖环没有双键。如果吡喃糖1号碳上的异头羟基已经变为OR基团则被称为吡喃糖苷。

Hexoses 己糖

The hexoses also exist primarily in ring forms under physiological conditions.

As with the aldopentoses, two kinds of rings are found: fivemembered furanoses and six-membered pyranoses.

In each case, a and b anomers are possible. An example, illustrated by Haworth projections, follows

(1) The four most common hexoses

These Haworth projections represent the D enantiomers.

Only the β anomers are shown

Hexoses can exist in boat and chair conformations.

Usually the chair is more stable.

5. A summary of terminology describing the structure of sugar molecules

Conformational isomers are distinguished from configurational isomers in that the former can interconvert without breaking and re-forming bonds.

Not shown are epimers, stereoisomers differing in their configuration about only one asymmetric carbon atom.

Derivatives of the Monosaccharides 单糖衍生物

1. Sugar phosphates (Phosphate Esters) 糖磷酸酯 (磷酸酯)

Important intermediates in metabolism, functioning as activated compounds in syntheses

Table 9.3 > Sugar phosphates (sugars that have added or substituted phosphate groups) are often used in biological systems to store or transfer energy. They also form the backbone for DNA and RNA (DNA having two sugar molecules, and RNA having just one).

In all cases, the standard state free energies of hydrolysis are less negative than the free energy of hydrolysis of ATP (-31kJ/mol) thus, ATP can act as a phosphate donor to monosaccharides.

On the other hand, because hydrolysis of the phosphate esters of sugars is thermodynamically favorable, these
derivatives can behave as “activated” compounds in many metabolic reactions.

Sugar phosphate esters are quite acidic, with $pK_{a}$ values for the two stages of phosphate ionization of about 1–2 and 6–7, respectively (see Table 9.3).

Consequently, these compounds exist under physiological conditions as a mixture of the monoanions and dianions.

Acids and Lactones (内酯)

内酯（英文：Lactone）即环状的酯，由一化合物中的羟基和羧基发生分子内缩合环化得到。内酯以五元（γ-内酯）及六元（δ-内酯）环内酯最为稳定，环内的角张力最小。

(1) Acids

Oxidation of monosaccharides can proceed in several ways, depending upon the oxidizing agent used.

• For example, mild oxidation of an aldose with alkaline Cu(II) (Fehlings solution) produces the aldonic acids（醛糖酸）, as in the following example:

(2) Lactone

Free aldonic acids, such as gluconic acid, are in equilibrium in solution with lactones, which are cyclic esters（环酯）, in this case involving the C1 carboxyl and the C5 hydroxyl.

Enzyme-catalyzed oxidation of monosaccharides gives other products, including uronic acids such as glucuronic acid, in which oxidation has occurred at carbon 6.

2. Alditols 醛糖醇

Reduction of the carbonyl group on a sugar gives rise to the class of polyhydroxy compounds（多羟基化合物） called alditols.

Important naturally occurring ones are erythritol（赤藓醇）, D-mannitol（D-甘露醇）, and D-glucitol（D-葡萄糖醇）, often called sorbitol

3. Amino sugars 氨基糖

In chemistry, an amino sugar (or more technically a 2-amino-2-deoxysugar) is a sugar molecule in which a hydroxyl group has been replaced with an amine group.

Glucosamine (葡糖胺，氨基葡糖) and galactosamine (半乳糖胺), derived from glucose and galactose (半乳糖)

Widely distributed in natural polysaccharides

4. Glycosides 糖苷

Introduction

糖苷（英语：Glycoside，简称苷，曾称为配糖体或甙（dài））是一类化合物，这类分子的其中一部分连着一个糖类部位。分子中非糖部分称作苷元（aglycon）

Elimination of water between the anomeric hydroxyl (异头羟基) of a cyclic monosaccharide and the hydroxyl group of another compound yields an O-glycoside，(the O signifying attachment at a hydroxyl).

单糖由直链变成环状结构时,羰基碳原子成为新的手性中心,导致C1差向异构化,产生两个非对映异构体。在环状结构中,半缩醛碳原子称为异头碳原子

The acetal bond formed is referred to as a glycosidic bond（糖苷键）

Unlike the anomers of the sugars themselves, the anomeric glycosides do not interconvert by mutarotation in the absence of an acid catalyst. This is a property that makes them useful in the determination of sugar configurations.

Many glycosides are found in plant and animal tissues. Some are toxic substances, in most cases because they act as inhibitors of enzymes involved in ATP utilization.

Oligosaccharides 寡糖

寡糖为碳水化合物，又称低聚糖，普遍由3-9个单糖分子聚合而成。寡糖普遍存在于动物细胞的细胞膜，并有着辨别其他细胞的功能。

If only a few monomer units are involved, we call the molecule an oligosaccharide

Oligosaccharides and polysaccharides are also referred to as glycans.

Table 9.5 ### 1. Disaccharides

The simplest and biologically most important oligosaccharides are the disaccharides, made up of two residues.

Functions of Disaccharides

As Table 9.5 shows, the disaccharides play many biological roles.

1. Some, like sucrose (蔗糖), lactose (乳糖), and trehalose (海藻糖), are soluble energy stores in plants and animals.
2. Others, like maltose (麦芽糖) and cellobiose (纤维二糖), can be regarded primarily as intermediate products in the degradation of much longer polysaccharides.
3. Still others, like gentiobiose (龙胆二糖), are found principally as constituents of more complex, naturally occurring substances.

Distinguishing Features of Different Disaccharides

1. The two specific sugar monomers involved, and their stereoconfigurations*.* （涉及两种特定的单糖及它们的立体异构体）

2. The carbons involved in the linkage.

   • The most common linkages are 1→1 (as in trehalose), 1→2 (as in sucrose), 1→4 (as in lactose, maltose, and cellobiose), and 1→6 (as in gentiobiose).
   • Note that all of these disaccharides involve the anomeric hydroxyl of at least one sugar as a participant in the bond

3. The order of the two monomer units, if they are different kinds.

   • The glycosidic linkage involves the anomeric carbon on one sugar, but in most cases the other is free.

     Thus, the two ends of the molecule can be distinguished by their chemical reactivity. For example: the glucose residue in lactose, having a free anomeric carbon and thus a potential free aldehyde group, could be oxidized by Fehling‘s solution; the galactose residue could not be.

   • Lactose is therefore a reducing sugar, and the glucose residue is at its reducing end The other end is called the nonreducing end.

   • In sucrose, neither residue has a potential free aldehyde group; both anomeric carbons are involved in the glycosidic bond. Therefore, sucrose is a nonreducing sugar.

4. The configuration of the anomeric hydroxyl group of each residue
   • This feature is especially important for the anomeric carbon(s) involved in the glycosidic bond. The configuration may be either (as in the disaccharides shown in Figure 9.15a) or (as in those in Figure 9.15b).
   • This difference may seem small, but it has a major effect on the shape of the molecule, and the difference in shape is recognized readily by enzymes.

Table 9.5  Figure 9.15(a)  Figure 9.15(b) #### Writing the Structure of Disaccharides

1. The sequence is written starting with the nonreducing end at the left, using the abbreviations defined in Table 9.4.
2. Anomeric and enantiomeric forms are designated by prefixes (e.g., α-, D-).
3. The ring configuration is indicated by a suffix (p for pyranose, f for furanose)
4. The atoms between which glycosidic bonds are formed are indicated by numbers in parentheses between residue designations (e.g.,（1 → 4） means a bond from carbon 1 of the residue on the left to carbon 4 of the residue on the right).

Table 9.4 As an example, we can write the structure of sucrose as: $$ \alpha - D - \text{Glc} p (1 \rarr 2) - \beta - D - \text{Fru} f $$ In many cases, the nomenclature is further shortened by omitting the D and L designations (except in the unusual cases in which L enantiomers are encountered) and by omitting the *p* and *f* suffixes when the monomers have their usual ring forms.

If only one carbon involved in the linkage between two residues is anomeric, the representation can be even more condensed because the anomeric configuration at the reducing end will equilibrate in solution.

For example, maltose can be represented as:
$$
\text{Glc} \alpha(1 \rarr 4) \text{Glc}
$$

2. Stability and Formation of the Glycosidic Bond 糖苷键

Metastable

Formation of the glycosidic bond between two monomers in an oligosaccharide is a condensation reaction, involving the elimination of a molecule of water.

The reaction as written above is thermodynamically unfavored. Instead, the hydrolysis of oligosaccharides and polysaccharides is favored under physiological conditions by a standard state free energy change of about 15 kJ/mol.

Like the phosphodiester bond in nucleic acid and amide bond in proteins, the glycosidic bond is metastable. (The hydrolysis is thermodynamically favored)

Enzymes control its hydrolysis.

Activated Monomers

As in protein or nucleic acid synthesis, activated monomers are required.

For glycan biosynthesis those activated monomers are usually nucleotide-linked sugars.

The activated sugar molecule in lactose biosynthesis is uridine diphosphate galactose (UDP-galactose or UDPGal), a nucleotide-linked sugar formed by reaction of uridine triphosphate with galactose-1-phosphate.

Example: Adding NTP

Glycan biosynthesis is carried out by glycosyltransferases (糖基转移酶), enzymes that transfer an activated glycosyl moiety (一部分；一半), to a specific position on a carbohydrate acceptor.

(1) Example: Enzymatic formation of lactose

The reaction shown occurs in the formation of milk in mammary tissue.

Galactose is phosphorylated by ATP, then transferred to uridine diphosphate (UDP).

UDP-galactose transfers galactose to glucose, with the accompanying cleavage of a phosphate bond.

The reaction is catalyzed by the enzyme lactose synthase.

(2) Exceptions

不使用UDP

Although both glycosyl transferases mentioned so far use uridine nucleotides for activation, there are

numerous exceptions.

For example, the biosynthesis of starch in plants uses adenosine diphosphate glucose (ADP-glucose or ADPG) as the activated nucleotide.

Another glycosyltransferase is responsible for the synthesis of sucrose in plants:
$$
\text{UDP-glucose + fructose-6-phosphate → surcose-6-phosphate + UDP}
$$

不使用Activated Monomers

An important feature of sucrose metabolism is that sucrose is involved in a glycan biosynthetic reaction that does not involve nucleotide-linked sugars.

Some bacteria carry out the synthesis of dextran（葡聚糖，右旋糖酐）, an α（1→6）-linked polymer of glucose with α（1→2）, α（1→3）, or α（1→4） branch points. The polymerization, catalyzed by dextran sucrase, uses sucrose itself as the substrate:
$$
n \text{ sucrose → glucose}_{n} \text{(dextran)} + n \text{ fructose}
$$

Oligosaccharides as Cell Markers – Glycoproteins 糖蛋白

Introduction of Glycoproteins

Function: Cell adhesion and recognition

Oligosaccharides and proteins can be linked to form glycoproteins in two ways:

1. O-linked glycans are attached via threonine or serine hydroxyls.
2. N-linked glycans via asparagine amino groups. (NO Glutamine)

• N-linked glycans are attached, usually through N-acetylglucosamine (N-乙酰葡糖胺), or sometimes through N-acetylgalactosamine (N-乙酰半乳糖胺), to the side chain amide group in an asparagine residue.

  A common sequence surrounding the asparagine is –Asn–X–Ser/Thr–, where X may be any amino acid residue.

• O-linked glycans are usually attached by an O-glycosidic bond between N-acetylgalactosamine and the hydroxyl group of a threonine or serine residue

Cell surface recognition factors:

1. Influenza Neuraminidase, a Target for Antiviral Drugs

The structure of the influenza virus:

The 13,600-nucleotide RNA genome is packaged within the sphere, about 120nm in diameter.

The spikes on the virion exterior include the hemagglutinin molecule and a spike that terminates in four neuraminidase molecules.

Hemagglutinin binding to sialic acid in cell surface

Neuraminidase release the binding

2. ABO Blood Group Antigens

The O oligosaccharide does not elicit antibodies in most humans.

The A and B antigens are formed by addition of GalNAc or Gal, respectively, to the O oligosaccharide.

Each of the A and B antigens can elicit a specific antibody.

R can represent either a protein molecule or a lipid molecule.

3. Rational design of neuraminidase inhibitors

Zanamivir and oseltamivir (Tamiflu) are structurally similar with sialic acid.

Partial model of the neuraminidase- zanamivir complex, showing amino acid residues that are close to the binding site for the inhibitor.

Polysaccharides 多糖

• The polymer is made from only one kind of monomer residue (β-D-glucose for cellulose), this kind of polymers are referred to as **homopolysaccharides **(同质多糖 )
• If two or more different monomers are involved, the polymer is called a heteropolysaccharide (杂多糖)

1. Storage polysaccharides

Introduction

Many structural polysaccharides (like structural proteins) form extended, regular secondary structures, well suited to the formation of fibers or sheets.

The only glycan polymers in which well-defined and complex sequences are found are some of the oligosaccharides attached to cell surfaces or those attached to specific glycoproteins. Because these oligomers serve to identify cells or molecules, they must convey information.

The principal storage polysaccharides are amylose (直链淀粉) and amylopectin (支链淀粉), which together constitute starch in plants, and glycogen, which is stored in animal and microbial cells.

Both starch and glycogen are stored in granules within cells

Glycogen is deposited in the liver, which acts as a central energy storage organ in many animals. Glycogen is also abundant in muscle tissue, where it is more immediately available for energy release.

(1) Why Store?

Glucose and even maltose are small, rapidly diffusing molecules, which are difficult to store. Were such small molecules present in large quantities in a cell, they would give rise to a very large cell osmotic pressure, which would be deleterious in most cases.

Therefore, most cells build the glucose into long polymers so that large quantities can be stored in a manner that prevents its diffusion and loss.

(2) How to Release

Most of the enzymes employed attack the chains at their nonreducing ends, releasing one glucose residue at a time.

Such “end-nibbling” (as opposed to internal cutting) prevents the continual breakup of the long polymers, which would lead to their complete solubilization.

The branched structure of both amylopectin and glycogen is such that each molecule has many nonreducing ends that can be attacked simultaneously (see Figure 9.18), allowing rapid mobilization of glucose when it is needed

Amylopectin (支链淀粉) and glycogen (糖原) [branched polysaccharides]

The α (1 → 4) linkages

The branches in glycogen are more frequent and shorter than those in amylopectin

Glycogen is usually of higher molecular weight

The structures of these two polysaccharides are very similar.

Figure 9.18 由于可以形成不同的linkage，比如（1 → 4）、（1 → 1）等等，所以支链淀粉和糖原在单体只有一种的情况下，可以形成支链，从而形成了复杂的结构

Amylose（直链淀粉）

Because of the α(1 → 4) link, each residue is angled with respect to the preceding residue, favoring a regular helical conformation (Figure 9.19).

The branched nature of amylopectin and glycogen inhibits the formation of helices because the helix requires 6 residues for each turn; there is a branch point about every 20–30 residues in amylopectin and about every 8–10 in glycogen.

The orientation of successive glucose residues favors helix generation.

Hydrogen bonds (not shown) stabilize the helix.

Branches inhibit helix formation.

Figure 9.19 对于Storage polysaccharides来说，稳定性并不是需要着重考虑的问题

支链存在的情况下，会不利于helix的形成

2. Structural polysaccharides

Introduction

Plants seem not to synthesize or use fibrous structural proteins but instead rely entirely on special polysaccharides; animals also use polysaccharides for structural purpose.

Cellulose and chitin are examples of structural polysaccharides.

Cellulose

(1) Structure

Like amylose, cellulose is a linear polymer of D-glucose (and hence is also a glucan), but in cellulose the sugar residues are connected by β(1 → 4) linkages (Figure 9.20).

The β(1 → 4) linkages of cellulose generate a planar structure.

The parallel cellulose chains are linked together by a network of hydrogen bonds.

Cellulose can exist as fully extended chains, with each glucose residue flipped by with respect to its neighbor in the chain. In this extended form, the chains can form ribbons that pack side by side with a network of hydrogen bonds within and between them.

Figure 9.20 α(1 → 4) 和 β(1 → 4)linkage的不同，造成了helix/planar的不同

Cellulose is not confined exclusively to the plant kingdom. In tunicates (尾索动物亚门), human connective tissue均有存在.

(2) Organization of plant cell walls

Microfibrils (微纤维) of cellulose are embedded in a matrix of hemicellulose (半纤维素).

Note that the fibers are laid down in a crosshatched pattern to give strength in all directions.

Chitin 几丁质

Chitin are used in chitin exoskeleton

The best known role of chitin, however, is in invertebrate animals; it constitutes a major structural material in the exoskeletons of many arthropods and mollusks.

Glycosaminoglycans（mucopolysaccharides） 糖胺聚糖/粘多糖

One group of polysaccharides is of major structural importance in vertebrate animals—the glycosaminoglycans, formerly called mucopolysaccharides.

Repeating structures of some glycosaminoglycans:

• In each case, the repeating unit is a disaccharide, of which two are shown for each structure.