1. Chapter 7 Carbohydrates and the Glycoconjugates of Cell Surfaces

2. Outline How are carbohydrates named?
What is the structure and chemistry of monosaccharides?
What is the structure and chemistry of oligosaccharides?
What is the structure and chemistry of polysaccharides?
What are glycoproteins, and how do they function in cells?
How do proteoglycans modulate processes in cells and organisms?
Do carbohydrates provide a structural code?

3. 7.1 How Are Carbohydrates Named?
Carbohydrates are hydrates of carbon
with the general formula (CH2O)n
Carbohydrates are classified in three groups:
Monosaccharides (simple sugars) - cannot be broken down into simpler sugars under mild conditions
Oligosaccharides (oligo = "a few“) - usually 2 to 10 simple sugar residues
Polysaccharides - polymers of the simple sugars

4. 7.2 What Is the Structure and Chemistry of Monsaccharides?
An organic chemistry review
Aldoses and ketoses contain aldehyde and ketone functions, respectively
Triose, tetrose, etc. denotes number of carbons
Aldoses with 3 or more carbon atoms and ketoses with 4 or more carbon atoms are chiral
Review Fischer projections and D,L system

5. 7.2 What Is the Structure and Chemistry of Monsaccharides?
Structure of a simple aldose and a simple ketose.

6. The Aldoses
The structure and stereochemical relationships of D-aldoses with three to six carbons. Know the ones in the boxes

7. The Ketoses
The structure and stereochemical relationships of D-ketoses with three to six carbons. Know the ones in the boxes.

8. Cyclic monsaccharide structures and anomeric forms
Glucose (an aldose) can cyclize to form a cyclic hemiacetal
Fructose (a ketose) can cyclize to form a cyclic hemiketal
When hemiacetals and hemiketals are formed, the carbonyl carbon atom becomes an asymmetric center
Isomers of monosaccharides that differ only in their configuration about that asymmetric carbon are called anomers
Cyclic form of glucose is a pyranose
Cyclic form of fructose is a furanose

9. Monosaccharides Exist in Cyclic, Anomeric Forms

10. 7.2 What Is the Structure and Chemistry of Monsaccharides?

11. Monosaccharides Can Be Converted to Several Derivative Forms
A variety of chemical and enzymatic reactions produce derivatives of the simple sugars
Some of the most common are:
Sugar acids
Sugar alcohols
Deoxy sugars
Sugar esters
Amino sugars
Acetals, ketals, and glycosides

12. Monosaccharide Derivatives
Reducing sugars are sugars with free anomeric carbons - they will reduce oxidizing agents, such as peroxide, ferricyanide and some metals (Cu2+ and Ag+).
These redox reactions oxidize the sugar to a sugar acid.
Glucose is a reducing sugar - so these reactions are the basis for diagnostic tests for blood sugar

13. Monosaccharides Can Be Converted to Several Derivative Forms

14. More Monosaccharide Derivatives
Sugar alcohols are formed by mild reduction of sugars
Deoxy sugars: constituents of DNA, etc.
Sugar esters: phosphate esters like ATP are important
Amino sugars contain an amino group in place of a hydroxyl group
Acetals, ketals and glycosides: basis for oligo- and polysaccharides

15. Sugar Alcohols

16. Deoxy Sugars
Deoxy sugars are monosaccharides with one or more hydroxyl groups replaced by hydrogens
2-Deoxy-D-ribose is a constituent of DNA
Rhamnose is a component of ouabain, a toxic “cardiac glycoside”
Fucose is a component of some cell walls

17. Amino Sugars Sugars with an amino group at C-2 are amino sugars.
They are found in many oligosaccharides and polysaccharides.

18. Muramic acid
Muramic acid is a component of the polysaccharides of cell membranes of higher organisms and also bacterial cell walls.
Muramic acid is a glycosamine linked to a 3-carbon acid at C-3.
(Murus is Latin for “wall”.)

19. Sialic acids
The N-acetyl and N-glycolyl derivatives of neuraminic acid are known as sialic acids.

20. Acetals and Ketals
Acetals and ketals can be formed from hemiacetals and hemiketals, respectively.

21. Glycosides
The pyranose and furanose forms of monosaccharides react with alcohols in dehydration synthesis reactions to form glycosides, with retention of the α- or β-configuration at the C-1 carbon. The new bond formed is called a glycosidic bond.

22. 7.3 What is the Structure and Chemistry of Oligosaccharides?
Disaccharides are the simplest oligosaccharides
Two monosaccharides linked by a glycosidic bond
Each unit in an oligosaccharide is termed a residue
Each of the structures in Figure 7.18 is a “mixed acetal”, with one hydroxyl provided intramolecularly and one hydroxyl from the other monosaccharide
Each of these (except for sucrose) possesses one free unsubstituted anomeric carbon, and is thus a reducing sugar
Sucrose is not a reducing sugar – it does not have a free anomeric carbon

23. 7.3 What is the Structure and Chemistry of Oligosaccharides?

24. 7.3 What is the Structure and Chemistry of Oligosaccharides?
Know the important features
Be able to identify anomeric carbons and reducing and nonreducing ends
Note carefully the nomenclature of links. Be able to recognize alpha(1,4), beta(1,4) linkages, etc., in structures.

25. 7.4 What is the Structure and Chemistry of Polysaccharides?
Functions: storage, structure, recognition
Nomenclature for polysaccharides is based on their composition and structure
Homopolysaccharide – a polysaccharide that contains only one kind of monosaccharide
Heteropolysaccharide – a polysaccharide made of several monosaccharides
Starch and glycogen are storage molecules
Chitin and cellulose are structural molecules
Cell surface polysaccharides are recognition molecules

26. Starch A plant storage polysaccharide
Two forms: amylose and amylopectin
Most starch is 10-30% amylose and 70-90% amylopectin
Branches in amylopectin every residues
Amylose has alpha(1,4) links, one reducing end
The branches in amylopectin are α(1→6).

27. Amylose and Amylopectin are energy storage molecules in plants

28. The Structure of Amylose
Amylose is poorly soluble in water, but forms micellar suspensions
In these suspensions, amylose is helical
Iodine fits into the helices to produce a blue color

29. Why Branching in Starch?
Consider the phosphorylase reaction
Phosphorylase releases glucose-1-P products from the amylose or amylopectin chains
The more branches, the more sites for phosphorylase attack
Branches in amylopectin provide a mechanism for quickly releasing (or storing) glucose units for (or from) metabolism

30. The Phosphorylase Reaction Releases Glucose Units for Metabolic Energy

31. The glucose storage device in animals
Glycogen
The glucose storage device in animals
Glycogen constitutes up to 10% of liver mass and 1-2% of muscle mass
Glycogen is stored energy for the organism
Only difference from amylopectin: even more highly branched
Alpha(1,6) branches every 8-12 residues
Like amylopectin, glycogen gives a red-violet color with iodine

32. Structural Polysaccharides
The composition of structural polysaccharides is similar to storage polysaccharides
But small structural differences greatly influence properties
Starch and glycogen linkages consist primarily of α(1→4) linkages.
Cellulose consists of β(1→4) linkages

33. Cellulose Provides Physical Structure and Strength to Plants
Cellulose is a structural polysaccharide
It is the most abundant natural polymer in the world
It is found in the cell walls of nearly all plants
The wood and bark of trees are insoluble, highly organized structures formed from cellulose and lignin
Cotton is almost pure cellulose
Cotton acetates, made from the action of acetic anhydride on cellulose, are used in dresses, lingerie, and other clothing

34. The Structural Difference Between Amylose and Cellulose
(a) Amylose prefers a helical conformation (due to its bent α(1→4) linkages. (b) Cellulose, with β(1→4) linkages, can adopt a fully extended conformation.

35. The Structure of Cellulose
The structure of cellulose, showing the hydrogen bonds (blue) between the sheets, which strengthen the structure.
Intrachain H-bonds in red; interchain H-bonds in green.

36. Other Structural Polysaccharides
Chitin – found in the exoskeletons of crustaceans, insects and spiders, and cell walls of fungi
It is similar to cellulose, but C-2s are N-acetyl
Cellulose strands are parallel; chitins can be parallel or antiparallel

37. Structures of cellulose, chitin and mannan
Like cellulose, chitin and mannan form extended ribbons and pack together efficiently, taking advantage of multiple hydrogen bonds.

38. Glycosaminoglycans – Linear Chains of Repeating Disaccharides
Glycosaminoglycans are linear chains of repeating disaccharides in which one unit is an amino sugar and one or both is negatively charged.

39. Functions of Glycosaminoglycans
Heparin, with a very high negative charge, is a natural anticoagulant.
Hyaluronates (consisting of up to 25,000 disaccharide units) are components of the vitreous humor of the eye and of synovial fluid, the lubricant fluid of the body’s joints
Chondroitins and keratan sulfate are found in tendons, cartilage, and other connective tissue
Dermatan sulfate is a component of the extracellular matrix of skin
Glycosaminoglycans are constituents of proteoglycans (discussed later in this chapter)

40. Composed of 1 or 2 bilayers and peptidoglycan shell
Bacterial Cell Walls
Composed of 1 or 2 bilayers and peptidoglycan shell
Gram-positive: One membrane phospholipid bilayer and thick peptidoglycan outer shell
Gram-negative: Two membrane phospholipid bilayers with thin peptidoglycan shell in between
Gram-positive: pentaglycine bridge connects tetrapeptides
Gram-negative: direct amide bond between tetrapeptides

41. The Structure of Peptidoglycan

42. The Structure of Gram-positive Peptidoglycan

43. The Cell Wall of Gram-positive Bacteria

44. The Cell Wall of Gram-negative Bacteria

45. Animals Display a Variety of Cell Surface Polysaccharides
Animal cell surfaces contain an incredible diversity of glycoproteins and proteoglycans
These polysaccharide structures regulate cell-cell recognition and interaction
The uniqueness of the "information" in these structures is determined by the enzymes that synthesize these polysaccharides

46. 7.5 What Are Glycoproteins, and How Do They Function in Cells?
May be N-linked or O-linked
N-linked saccharides are attached via the amide nitrogens of asparagine residues
O-linked saccharides are attached to hydroxyl groups of serine, threonine or hydroxylysine

47. The Structure of O-Linked Saccharides

48. O-linked Saccharides of Glycoproteins
The O-linked saccharides often adopt extended conformations to lift the functional domains of these proteins above the membrane surface.

49. The Structure of N-Linked Saccharides
Figure 7.32 The carbohydrate moieties of glycoproteins may be linked to the protein via asparagine residues (in N-linked saccharides).

50. The Structure of N-Linked Saccharides
Figure 7.32 N-linked glycoproteins are of three types: high mannose, complex, and hybrid, the latter of which combines structures found in the high mannose and complex saccharides.

51. Functions of N-linked Oligosaccharides
Many functions known or suspected
Oligosaccharides can alter the chemical and physical properties of proteins
Oligosaccharides can stabilize protein conformations and/or protect against proteolysis
Cleavage of monosaccharide units from N-linked glycoproteins in blood targets them for degradation in the liver

52. Structures of Proteoglycans
Structure of rat cartilage matrix proteoglycan. This molecule is highly hydrated. Compression of cartilage (as in walking) squeezes water out of the cartilage tissue to cushion the joint. Water is reabsorbed when the stress and compression diminishes.

53. Lectins are proteins that bind carbohydrates with high specificity and high affinity
Sugars are the “letters” of the sugar code. Lectins are the translators of the sugar code. Many processes, such as cell migration, cell-cell interactions, immune responses, and blood clotting, depend on information transfer using this code.