Table of Contents
Fundamentals of Biochemistry
Biochem 380 - Fall 2006
Lecture 024
Outline
- Announcements
- Questions from previous lecture
- Section 8.6: Polysaccharides
- Section 8.7: Glycoconjugates
Announcements
- Lecture 23 notes are online
- Reminder: homework problems for Chapter 8: 1, 5, 8, 10, 11, 12
- Quiz on Friday will cover Chapters 7 and 8
Questions
- Any questions on the material from the previous lecture?
Section 8.6: Polysaccharides
- Polysaccharides are longer chains built from carbohydrate molecules. With the elimination
of water, the (CH2O)n formula does not strictly hold, so the more general
term glycan is also used when referring to these polymers
- We'll look at a few types of polysaccharides, including starch, cellulose
and chitin
Starch
- Starch is a storage molecule, a homopolysaccharide (homoglycan) produced in plants. It is
stored in granules ranging from 3 to 100 µm in size
- There are two types of starch: amylose and amylopectin.
- Both of these are polymers of D-glucose residues, connected by α-(1→4) glycosidic
bonds. Amylose is unbranched, and amylopectin is a branched polymer, with additional chains attached
by α-(1→6) bonds
Amylose
- Amylose is an energy storage molecule that can remain stable in the absence of water
- In solution, it becomes hydrated and can adopt an open, helical structure
- The bent, open structure of the amylose chain facilitates access by enzymes to hydrolyze the
bonds, releasing smaller units for energy consumption
- Amylose molecules range in size from 100 to 1000 glucose residues
Amylopectin
- Amylopectin demonstrates a property of polymers quite distinct from that of proteins.
It has a branched chain structure formed by attachment of additional chains at the C6 carbons of the glucose
residues, with α-(1→6) bonds
- On average, a branch is added at every 25 residues, and the branch chains contain about 15 to 25
glucose residues
- Typical sizes of amylopectin molecules vary from 300 to 600 glucose residues in total
Cleavage of Amylopectin
- The presence of branches increase the number of locations at which residues can be cleaved from the molecule.
Cleavage is done by two different enzymes: α-amylase and β-amylase
- α-amylase is an endoglycosidase, which cleaves at internal locations of the polymer.
β-amylase is an exoglycosidase, which releases maltose units from the nonreducing ends of amylopectin
Cellulose
- Cellulose is a structural polysaccharide that is a major component of the rigid cell walls in plants.
It is one of the most abundant biomolecules on Earth
- Like amylose, it is a linear polymer of glucose molecules, but they are connected by β-(1→4)
linkages. These produce rigid, extended chains in which each residue is flipped 180° relative to its neighbors
- Extensive hydrogen bonding takes places between residues, leading to the formation of sheets and bundles
with high mechanical strength
Chitin
- Chitin is another structural molecule that is similar to cellulose, and is probably the second most
abundant biomolecule on the planet
- It is a homoglycan used in the exoskeletons of insects, arachnids, crustaceans and other arthropods.
It is also found in the cell walls of fungi and algae
- Chitin consists of N-acetylglucosamine (GlcNAc) residues linked together by β-(1→4) bonds
Section 8.7: Glycoconjugates
- Starch, cellulose and chitin are all examples of homoglycans, or polysaccharides composed of
a single type of monomer
- When multiple types of monosaccharide units are joined together, the resulting
polysaccharides are heteroglycans
- Polysaccharides are often joined to proteins to produce glycoconjugates. The polysaccharides
in such molecules are usually heteroglycans, where a variety of sugars and sugar derivatives can be used
to provide additional chemical and physical properties
- Glycoconjugates can be organized into three main types:
- Proteoglycans (mostly carbohydrate, some protein)
- Peptidoglycans (short peptides joined to polysaccharide chains)
- Glycoproteins (proteins with short carbohydrate chains)
Proteoglycans
- Proteoglycans are proteins joined to a type of polysaccharide called glycosaminoglycans
- As the name implies, glycosaminoglycans contain amino sugars, along with other types of monosaccharides
- An example is aggrecan, the major proteoglycan of cartilage. This proteoglycan exists as
part of a network of connecting molecules that includes additional glycosaminoglycan chains and linker proteins
- Proteoglycans are typically found in the extracellular matrix, in connective tissues of multicellular
animals. These molecules are often highly hydrated and occupy a large volume because their
glycosaminoglycan components contain polar and ionic groups
- This hydration produces elasticity and resistance to compression, allowing the cartilage and joints
to absorb and recover from mechanical shock and vibration
Glycosaminoglycans
- Glycosaminoglycans are unbranched heteroglycans that contain linked disaccharide units
- One component of the disaccharide unit is an amino sugar, such as galactosamine (GalN) or glucosamine (GlcN).
The other sugar is usually an alduronic acid such as glucuronic acid (GlcUA), as in the case of hyaluronic acid,
shown above
- In addition to the carboxylate groups of GlcUA residues, negative charges are contributed by sulfate groups
in glycosaminoglycans such as chondroitin sulfate and keratin sulfate
Proteoglycans in Cartilage
- The proteoglycan aggregates in cartilage consist of a central strand of hyaluronic acid, connected
to linker proteins that attach to core proteins of aggrecan
- Aggrecan is a proteoglycan protein with about 30 molecules of keratin sulfate and 100 molecules of
chondroitin sulfate attached. The resulting 'bottle brush' structure is highly hydrated and resistant
to mechanical stress
Glucosamine and Osteoarthritus
- With old age, cartilage begins to deteriorate, resulting in abnormal wear and stress on the joints and bones
in the arms and legs
- The resulting joint pain and inflammation are symptoms of the disease osteoarthritus, which
afflicts at least 20 million Americans, and with the coming aging of the baby boomers, is expected to double
over the next two decades
- Although analgesics such as aspirin and acetaminophen are commonly used to reduce the pain of
osteoarthritus, recent studies have indicated that nutritional supplements of glucosamine and chondroitin
sulfate may help to reduce these symptoms as well, although mostly in moderate and severe cases
Peptidoglycans
- Peptidoglycans are polysaccharides linked to small peptides. Many bacterial cell walls are built
with a type of peptidoglycan that contains a heteroglycan of N-acetylmuramic acid (MurNA) and N-acetylglucosamine
(GlcNAc). These are linked together by two peptides, a tetrapeptide and a pentaglycine bridge. The antibiotic
penicillin works be interfering with the final linkage reaction between the bridge and the tetrapeptide
Glycoproteins
- Glycoproteins are the third kind of glycoconjugates. These are proteins with carbohydrate chains attached
that can vary in length from 1 to 30 residues
- These oligosaccharide chains can contain several different kinds of sugars. In eukaryotes, eight
kinds of sugars are mostly used: fucose, galactose, glucose, mannose, GalNAc, GlcNAc, sialic acid and xylose
- The chains can be attached to the proteins in two main ways: either to a side chain with a hydroxyl group
such as serine (O-linked) or to the amide group of asparagine (N-linked)
- Many O-linked oligosaccharides are found in the mucins, which are glycoproteins in mucous. N-linked
oligosaccharides include high-mannose, complex and hybrid classes
Blood Types
- The different blood types in humans were discovered in 1901. Three main blood types exist: A, B and O.
They are determined by the existence of enzymes which catalyze the addition of sugar groups on to glycoproteins
on cell surfaces
- The core structure consists of the H antigen, which is present in all blood types. This can be modified
by the addition of a GalNAc residue to produce the A blood type, if the gene for the A enzyme is present
- Similarly, the presence of the gene for the B enzyme will result in the addition of a Gal sugar,
producing the B blood type
- If neither gene is present, the blood type will be type O
Questions
- Questions about the material covered today?
References
- Osteoarthritis of the Knee,
David T. Felson, M.D., M.P.H.,
N ENGL J MED 354:8, www.nejm.org, February 23, 2006
(A case vignette about a patient with osteroarthritus, her evaluation and treatment)
- Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis,
Daniel O. Clegg et al.,
N ENGL J MED 354:8, www.nejm.org, February 23, 2006
(Presents the results of a multi-center double-blind clinical trial to evaluate the use of glucosamine and
chondroitin sulfate for treatment of knee pain from osteoarthritus)
Next Lecture: Sections 9.1 - 9.2
