Oligosaccharides & Polysaccharides

Oligosaccharides

  • Molecules made of 2-10 monosaccharides chemically bonded.
  • Monosaccharides in larger molecules are called "residues."
  • Subcategorized by the number of monosaccharide residues.
    • Disaccharide: 2 monosaccharide residues.
    • Trisaccharide: 3 monosaccharide residues.

Disaccharide Nomenclature

  • Structures are named with reducing ends on the right. Locate the reducing ends accordingly.
  • Configuration of the anomeric carbon joining the first monosaccharide to the second is given (left to right).
  • Non-reducing residue named; "furano" or "pyrano" prefixes distinguish five- and six-membered ring structures.
  • Carbons joined by the glycosidic bond are in parentheses, with an arrow connecting the numbers.
  • The second residue is named.
  • Subsequent residues and glycosidic bonds described using the same conventions.
  • Non-reducing disaccharides are named as glycosides, not glycoses.
  • Double-headed arrow denotes sugars joined by anomeric carbons; stereochemistry must be specified at both anomeric carbons.

Important Disaccharides

  • Sucrose: table sugar - glucose and fructose (alpha linkage)
  • Lactose: milk sugar - galactose and glucose (beta linkage)
  • Maltose: malt sugar, from starch breakdown - 2 glucoses
  • Cellobiose: from partial hydrolysis of cellulose, faintly sweet

Maltose Formation

  • Bond formed between two α-D-glucose monosaccharides.
  • Step 1: H atom removed from the hydroxyl group (OH) bonded to the anomeric carbon of the left-most residue; OH removed from any carbon in the right-most residue. The H and OH form a water molecule.
  • Step 2: New bond drawn from the oxygen (O) remaining on the anomeric carbon in the left-most residue to the carbon from which the OH was removed in the right-most residue; oriented in the same direction as the bond to OH that was removed.
  • The disaccharide formed is called maltose.
  • This method can form a bond between any two sugar residues.
  • Maltose is purified from germinated grains; brewers stop barley grain germination to get malted barley.
  • Malted barley has a high concentration of fermentable maltose which is used in making beer and certain adult beverages.
  • Also used as sweetener and thickener in frozen beverages called "malts."

Glycosidic Bond

  • Covalent bonding pattern linking the anomeric carbon of one residue to an oxygen, then to a carbon in the other sugar residue.
  • Glycosidic bonds described using alpha (α) or beta (β).
    • Alpha (α): bond from the anomeric carbon to the oxygen (O) in the glycosidic bond is oriented downward from the ring.
    • Beta (β): bond from the anomeric carbon to the oxygen (O) in the glycosidic bond is oriented upward from the ring.
  • Maltose has the "α" designation.
  • A glycosidic bond is characterized by its α/β orientation and which two carbons are linked by the glycosidic bond.
  • The glycosidic bond in maltose is classified as α-(1→4).
  • The numbers and arrow in the parenthesis begins with the anomeric carbon position number where the glycosidic bond originates, then the arrow followed by the carbon position number where the glycosidic bond terminates in the other residue.
  • Maltose has the (1-4) designation because the glycosidic bond links the anomeric carbon (carbon number 1) to carbon number 4 of the other residue.
  • The glycosidic bond in maltose has the α designation because it was constructed from α-monosaccharides. A glycosidic bond constructed from β-monosaccharides will have the β orientation.

Mutarotation

  • Oligosaccharides, such as maltose, with a residue that contains a hemiacetal anomeric carbon will interconvert (mutarotate) between closed anomers and an open-form. This residue can no longer interconvert between open-chain and cyclic forms and is locked in cyclic form.
  • Mutarotation does not change the α/β designation of a glycosidic bond.
  • If the open-chain form of an oligosaccharide contains an aldehyde group, it will give a positive Benedict's test.
  • Since the anomeric carbon in the right-most residue is a hemiacetal and undergoes mutarotation, the orientation of the OH and H that are bonded to it constantly changes.

Cellobiose Formation

  • Glycosidic bond connects two β-D-glucose monosaccharides.
  • Step 1: An H atom is removed from the hydroxyl group (OH) that is bonded to the anomeric carbon of the left-most residue, and an OH is removed from any carbon in the right-most residue. H and OH combine to form a water molecule.
  • Step 2: A new bond is drawn from the oxygen (O) that remains on the anomeric carbon in the left-most residue to the carbon from which the OH was removed in the right-most residue. This new bond is oriented in the same direction as was the bond to OH that was removed.
  • Cellobiose has the "β" designation because the bond from the anomeric carbon to the oxygen (O) of the glycosidic bond is oriented upward from the ring.
  • Cellobiose has the (1-4) designation because the glycosidic bond links the anomeric carbon (carbon number 1) to carbon number 4 of the other residue.
  • Since starting with β-monosaccharides, the glycosidic bond has the β orientation.

Lactose

  • Disaccharide containing a β-D-galactose residue bonded to a D-glucose residue by a β-(1-4) glycosidic bond.
  • The anomeric carbon in the right-most residue undergoes mutarotation, and can be drawn with the OH in either the α or β orientation.

Lactose Intolerance

  • Inability to metabolize lactose, due to a lack of the required enzyme lactase in the digestive system.
  • Estimated that 75% of adults worldwide show some decrease in lactase activity during adulthood.
  • Frequency of decreased lactase activity ranges from as little as 5% in northern Europe, up to 71% for Sicily, to more than 90% in some African and Asian countries.
  • Disaccharides cannot be absorbed through the wall of the small intestine into the bloodstream, so in the absence of lactase, lactose remains uncleaved and passes intact into the colon.
  • Bacteria in the human digestive system ferment lactose in the absence of lactase.
  • Part of the β-galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers; present predominantly along the brush border membrane of the differentiated enterocytes lining the villi of the small intestine.

LAC Operon

  • beta-galactosidase: hydrolyzes bond between glucose and galactose; coded by LacZ gene.
  • Lactose Permease: spans the cell membrane and brings lactose into the cell; coded by LacY gene.
  • Thiogalactoside transacetylase: function not known; coded by LacA gene.

Effects of Lactose Intolerance

  • The operons of enteric bacteria quickly switch over to lactose metabolism, and results in in vivo fermentation, producing copious amounts of gas (hydrogen, carbon dioxide, and methane).
  • May cause abdominal symptoms: stomach cramps, nausea, bloating, acid reflux and flatulence.
  • Presence of lactose and its fermentation products raises the osmotic pressure of the colon contents.

Lactose Intolerance Symptoms

  • Abdominal bloating
  • Abdominal cramps
  • Diarrhea
  • Floating stools
  • Foul-smelling stools
  • Gas (flatulence)
  • Malnutrition
  • Nausea
  • Slow growth
  • Weight loss

Managing Lactose Intolerance

  • Most people with low lactase levels can tolerate 2-4 ounces of milk at one time.
  • Easier to digest milk products:
    • Buttermilk and cheeses (less lactose than milk)
    • Fermented milk products, such as yogurt
    • Goat's milk (with meals, supplemented with essential amino acids and vitamins for children)
    • Ice cream, milkshakes, and aged or hard cheeses
    • Lactose-free milk and milk products
    • Lactase-treated cow's milk for older children and adults
    • Soy formulas for infants younger than 2 years
    • Soy or rice milk for toddlers

Sucrose

  • Table sugar; disaccharide formed from α-D-glucose and β-D-fructose.
  • Glycosidic bond is α,β-(1↔2) because the stereochemistry at the anomeric carbon of the glucose residue (position number 1) has the α orientation, and the anomeric carbon of the fructose residue (position number 2) has the β orientation.
  • Involves two anomeric carbons.
  • Neither residue contains a hemiacetal carbon; cannot interconvert/mutarotate between open-chain and cyclic forms, both are "locked" in their cyclic forms.
  • Gives a negative Benedict's test; not a reducing sugar.
  • Overconsumption linked to tooth decay and obesity.

Sucralose

  • Zero-calorie artificial sweetener, approximately 600 times as sweet as sucrose.
  • Stable under heat and over broad pH range.
  • Organochloride (or chlorocarbon); not known to be toxic in small quantities and is extremely insoluble in fat; cannot accumulate in fat like chlorinated hydrocarbons and does not break down or dechlorinate.
  • Some concern about effect of sucralose on the thymus: two studies on rats found a significant decrease in mean thymus weight at high doses (3000 mg/kg/day for 28 days).
  • For a 150 lb (68.2 kg) human, this would mean an intake of nearly 205 grams of sucralose a day, which is equivalent to more than 17,200 individual Splenda packets/day for approximately one month.

Raffinose and Stachyose

  • Found together in many foods, most notably legumes (e.g. beans and peanuts) and cruciferous vegetables (e.g. broccoli, cauliflower, brussels sprouts, and cabbage).
  • Monogastric (single stomach) animals, including humans, pigs, and poultry, cannot completely digest raffinose or stachyose because we do not have the enzyme, α-galactosidase, that is needed to break their α-galactose glycosidic bonds.
  • Raffinose and stachyose pass through the digestive track without being completely digested, and can be fermented by digestive microbes to produce gases.
  • The α-galactosidase enzyme can be taken as a nutritional supplement to avoid the discomfort of bloating and flatulence.
  • Raffinose is categorized as a trisaccharide because it contains three monosaccharide residues: a galactose, a glucose, and a fructose residue.
  • Contains an α-(1-6) glycosidic bond.
  • Stachyose is categorized as a tetrasaccharide because it contains four monosaccharide residues: two galactose residues, a glucose residue, and a fructose residue.

Sweeteners

  • Compound added to food to impart the sweet taste of sucrose, but with significantly fewer calories.
  • Classified as "artificial sweeteners” or “natural sweeteners."
    • Natural sweeteners: carbohydrates, naturally occurring carbohydrate derivatives, or other naturally occurring non-carbohydrate compounds.
    • Artificial sweeteners: synthesized in commercial laboratories; do not occur in nature.
  • Sucrose is the reference standard for "sweetness."
  • A "sweetness value" of 100 is assigned to sucrose, and then other sweeteners are assigned sweetness values relative to the taste of the same mass of sucrose.
  • Approved sweeteners for sale in the US: stevia, aspartame, sucralose, neotame, acesulfame potassium (Ace-K), saccharin, and advantame.
  • None have ever been shown to cause cancer in humans.

Polysaccharides

  • Composed of more than ten residues.
  • Residues can be monosaccharides or monosaccharide derivatives.
  • Subcategorized as either homopolysaccharides or heteropolysaccharides.
    • Homopolysaccharides: composed of only one type of residue.
    • Heteropolysaccharides: composed of more than one type of residue.

Homopolysaccharides

  • Examples: Cellulose, Starch (amylose & amylopectin), Glycogen & Chitin
Cellulose
  • Composed of multiple D-glucose residues (only), bonded to each other by B-(1-4) glycosidic bonds.
  • A cellulose molecule contains hundreds (sometimes thousands) of glucose residues.
  • Found in the cell walls of green plants, some algae, and oomycetes.
  • Accounts for approximately 45% of the mass of dry wood and about 90% of the mass of cotton fibers.
  • Major industrial use is the production of paper.
  • Humans lack the enzyme necessary to break the glucose-glucose β-(1-4) glycosidic bond, therefore we cannot metabolize cellulose to get energy and classified as a dietary fiber.
  • Some animals (ruminants and termites) are able to metabolize cellulose because they contain bacteria in their digestive track that can do so.
  • Acts as a bulking agent for feces, and eases defecation.
  • Much of the rigidity of plant cell walls comes from the strong intermolecular forces, especially hydrogen bonding, that are present between the very long and straight cellulose molecules that lie next to each other in a side-by-side fashion.
Starch
  • Common component of plants.
  • Excess glucose produced in photosynthesis is stored as starch in plants.
  • Composed of two different polysaccharides, both of which are homopolysaccharides: amylose and amylopectin.
Amylose
  • Composed of multiple D-glucose residues (only), bonded to each other by α-(1-4) glycosidic bonds.
  • An amylose molecule contains hundreds to many thousands of D-glucose residues.
  • Amylose and cellulose have the same bonding pattern except for the α vs. β orientation of their glycosidic bonds.
  • Humans have digestive enzymes (called amylases) that are capable of breaking glucose-glucose α-(1-4) glycosidic bonds, and residues in amylose form a helical coil (helix).
Amylopectin
  • Also a homopolysaccharide composed of multiple D-glucose residues (only), bonded to each other by α-(1-4) glycosidic bonds (as in amylose) with other chains of D-glucose that branch from carbon number 6.
  • Branching occurs as an α-(1-6) glycosidic bond.
  • An amylopectin molecule typically contains 2,000 to 200,000 D-glucose residues.
  • Branching usually occurs every 24 to 30 glucose residues.
  • Because of branching, amylopectin molecules have a large number of endpoints.
  • Since the amylase digestive enzymes attach to starch molecules at the endpoints, amylopectin can be digested more quickly than amylose.
  • Starch contains about 70-80% amylopectin and 20-30% amylose.
  • One of the three amylase digestive enzymes is capable of breaking the branching α-(1-6) glycosidic bonds.
Glycogen
  • Plants store excess glucose as starch; animals and fungi store excess glucose as glycogen.
  • A homopolysaccharide composed of multiple D-glucose residues (only).
  • Almost identical to amylopectin, the only difference is that it branches more frequently.
  • Branching in glycogen usually occurs every 8 to 10 glucose residues.
  • In humans, glycogen is made and stored primarily in liver and muscle cells.
Chitin
  • Chitin is a linear homopolysaccharide composed of N-acetylglucosamine residues in β linkages.
  • Chitin differs chemically from cellulose only in the acetylated amino substituent at carbon 2.
  • It forms extended fibers that are similar to those of cellulose, and is found principally in hard exoskeletons of arthropods and occurs naturally in both parallel and antiparallel stacking arrangements.

Heteropolysaccharides

  • Composed of more than one type of residue.
  • Residues can be monosaccharides and/or monosaccharide derivatives.
  • Example: Hyaluronic acid
Hyaluronic Acid
  • Contains D-glucuronic acid and N-acetyl-D-glucosamine residues, connected to each other in the bonding pattern.
  • Residues are connected by alternating B-(1-4) and B-(1-3) glycosidic bonds.
  • A hyaluronic acid molecule can contain up to about 50,000 residues.

Glycoproteins

  • Proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains.
  • The carbohydrate is attached to the protein in a cotranslational or posttranslational modification (glycosylation).
  • In proteins that have segments extending extracellularly, the extracellular segments are often glycosylated.
  • Glycoproteins are often important integral membrane proteins, where they play a role in cell-cell interactions.
  • Glycoproteins also occur in the cytosol, but their functions and the pathways producing these modifications in this compartment are less well-understood.
  • There are two types of glycoproteins:
    • In N-glycosylation, the addition of sugar chains can happen at the amide nitrogen on the side chain of asparagine.
    • In O-glycosylation, the addition of sugar chains can happen on the hydroxyl oxygen on the side chain of hydroxylysine, hydroxyproline, serine, or threonine.
  • The principal sugars found in human glycoproteins include:
    • β-D-Glucose Glc
    • β-D-Galactose Gal
    • β-D-Mannose Man
    • α-L-Fucose Fuc
    • N-Acetylgalactosamine GalNAc
    • N-Acetylglucosamine GlcNAc
    • N-Acetylneuraminic acid NeuNAc
    • Xylose Xyl
  • Examples of glycoproteins found in the body:
    • Mucins: secreted in the mucus of the respiratory and digestive tracts. The sugars attached to mucins give them considerable water-holding capacity and also make them resistant to proteolysis by digestive enzymes.
    • In the immune system:
      • White blood cell recognition molecules such as antibodies which interact directly with antigens
      • Molecules of the major histocompatibility complex (or MHC), which are expressed on the surface of cells and interact with T cells as part of the adaptive immune response.
    • Glycoprotein IIb/IIIa: an integrin found on platelets that is required for normal platelet aggregation and adherence to the endothelium.
    • The zona pellucida: which surrounds the oocyte, and is important for sperm-egg interaction.
    • Connective tissue: These help bind together the fibers, cells, and ground substance of connective tissue, and may also help components of the tissue bind to inorganic substances, such as calcium in bone.
    • Glycoprotein-41 (gp41) and glycoprotein-120 (gp120): HIV viral coat proteins.
  • Hormones that are glycoproteins include:
    • Follicle-stimulating hormone: Stimulates the follicle to produce estrogen
    • Luteinizing hormone: Stimulates the corpus luteum to produce progesterone.
    • Thyroid-stimulating hormone
    • Human chorionic gonadotropin: maintains the corpus luteum and allows the production of progesterone and estrogen until the placenta takes over this task