Carbohydrate Notes

Carbohydrates

Carbohydrates play several key roles:

  • Energy storage
  • Component of RNA and DNA backbones
  • Structural component in plant and bacteria cell walls
  • Can be linked to proteins and lipids

Monosaccharides

Monosaccharides are the simplest form of carbohydrates, defined as:

  • Aldehydes and ketones with at least two hydroxyl groups.
  • General formula: (CH<em>2O)</em>n(CH<em>2O)</em>n
  • The smallest monosaccharides contain 3 carbons and are called trioses.
    • Aldose: Contains an aldehyde group (e.g., glyceraldehyde).
    • Ketose: Contains a ketone group (e.g., dihydroxyacetone).

Triose Sugars: Aldose & Ketose

  • Glyceraldehyde (an aldose) and dihydroxyacetone (a ketose) are the two 3-carbon monosaccharides.

  • Glyceraldehyde has two chiral isomers, D-Glyceraldehyde and L-Glyceraldehyde and D-Glyceraldehyde are present in nature.

  • Dihydroxyacetone is achiral because it lacks a chiral carbon.

Isomers of Glyceraldehyde

  • D and L isomers exist for glyceraldehyde.
  • D isomers are more common in biological systems.
  • The structures of D-glyceraldehyde and L-glyceraldehyde are mirror images of each other.

Fischer Projections

  • Fischer projections are a way to represent the three-dimensional structure of molecules on a two-dimensional plane.
  • Vertical bonds project into the page, while horizontal bonds project out of the page.

More Complicated Monosaccharides

  • Monosaccharides can have 4, 5, 6, or 7 carbons (tetroses, pentoses, hexoses, and heptoses, respectively).
  • These sugars often have multiple chiral centers.
  • The number of possible stereoisomers for a compound with nn chiral centers is 2n2^n.
  • D and L symbols are used to denote the chiral carbon furthest from the ketone or aldehyde group.
  • Examples:
    • Aldotetroses: D-Erythrose, D-Threose
    • Aldopentoses: D-Ribose, D-Arabinose, D-Xylose, D-Lyxose
    • Aldohexoses: D-Allose, D-Altrose, D-Glucose, D-Mannose, D-Gulose, D-Idose, D-Galactose, D-Talose

Diastereoisomers

  • Diastereoisomers are stereoisomers that are not mirror images of each other.
  • For example, D-erythrose and D-threose are diastereoisomers.
  • They have the same configuration at C-3, but a different configuration at C-2.

Common Aldose Monosaccharides

  • Pentoses:
    • Ribose
  • Hexoses:
    • D-Glucose
    • D-Mannose
    • D-Galactose

Numbering Carbons in Aldose Sugars

The aldehyde carbon is designated as C1. Subsequent carbons are numbered sequentially.

Epimers

  • Epimers are sugars that differ in configuration at only one chiral carbon.
    • Glucose and mannose are epimers because they differ only at the C2 carbon.
    • Glucose and galactose are epimers because they differ only at the C4 carbon.

Learning Objectives – Ketose Monosaccharides

  • What is a tetrose, pentose, and hexose ketose monosaccharide?
  • Compare to an aldose monosaccharide, how many chiral carbons do they possess?
  • Draw the Fischer projection of D-fructose.

Ketose Sugars

  • The simplest ketose sugar is dihydroxyacetone.
  • Ketose sugars have fewer chiral centers than aldose sugars.
    • For example, D-erythrulose has one chiral center, while D-erythrose (an aldose) has two chiral centers.

D-Erythrose

  • D-Erythrose is an aldotetrose.
  • D-Glyceraldehyde is an aldotriose.

Common Ketose Sugar

  • Fructose (fruit sugar) is a common ketose.
  • Other examples include:
    • D-Psicose
    • D-Tagatose
    • D-Sorbose

Numbering Carbons in Ketose Sugars

  • The carbon nearest the ketone group is designated as C1.

Cyclization of Carbohydrates

  • In solution, ribose, glucose, and fructose form ring structures.
  • Aldehyde reacts with Alcohol to form Hemiacetal
  • Ketose reacts with Alcohol to form Hemiketal
  • Pyranose: six-membered ring
  • Furanose: five-membered ring
  • The number of chiral carbons increase when glucose forms a pyranose sugar.

Anomeric Carbon

  • The anomeric carbon is the new chiral center formed during cyclization.
  • α anomer: The OH group on the anomeric carbon is down (below the ring).
  • β anomer: The OH group on the anomeric carbon is up (above the ring).

Haworth Projections

  • Haworth projections are a way to represent the cyclic structure of monosaccharides.
  • Pyranose rings can form chair and boat configurations.
  • The chair configuration is favored due to reduced steric hindrance.

Hexose & Pentose Sugars Form Ring Structures

  • Ribose, glucose, and fructose sugars form rings and do not exist as open chains because ring formation is energetically more stable.
  • The basis of ring formation:
    • Aldehyde + Alcohol → Hemiacetal

Glucose

  • C1 aldehyde reacts with C5 hydroxyl group to form a 6-membered heterocyclic ring called a pyranose.
  • Pyranose resembles pyran.

Ketose Sugars

  • Also undergo a similar reaction.
  • Ketone + alcohol → hemiketal

Fructose

  • C2 keto group can react with either C-6 to form a 6-carbon ring or C-5 to form a 5-carbon ring.
  • The C5 ring is called furanose and resembles furan.

Haworth Projections

  • Haworth projections depict the cyclic form of sugars with the ring roughly perpendicular to the plane of the paper.
  • Groups are shown above or below the ring.
    • Examples: β-D-Ribose, β-2-Deoxy-D-ribose

Anomeric Carbon

  • Ring formation generates another chiral center, which becomes the anomeric carbon.
  • The OH group on the anomeric carbon (C1) is on the opposite side of the ring from the CH2OH group that designates the sugar as D or L.
  • Designations:
    • α: if OH is down (below the ring)
    • β: if OH is up (above the ring)

Glucose Anomers

  • In solution, glucose exists as a mixture of anomers:
    • 1/3 α anomer
    • 2/3 β anomer
    • Less than 1% open-chain form

Fructose Anomers

  • Can form α and β anomers at C-2.
  • Can form both pyranose and furanose rings.

Fructose & Ribose

  • In free solution, the pyranose form predominates.
  • The furanose form predominates in many derivatives.

Ribose

  • The furanose form of ribose is commonly seen in nucleotides.
  • In solution, ribose exists in various forms:
    • α-D-Ribopyranose
    • β-D-Ribopyranose
    • α-D-Ribofuranose
    • β-D-Ribofuranose

Pyranose Rings

  • Can form chair and boat configurations.
  • Chair form:
    • Substituents on the ring exist in two forms:
      • Axial: perpendicular to the ring
      • Equatorial: same plane as the ring

Axial Components

  • Sterically hinder each other if they emerge from the same side of the ring.
  • Equatorial components:
    • Less crowding, reduced steric hindrance

β-D-Glucose

  • The chair form predominates because axial positions are occupied by H atoms → less steric hindrance.

Furanose Rings - Envelope Form

  • Not planar
  • Four C atoms are nearly planar
  • The fifth C is ≈ 0.5A out of the plane

Glycosidic Bonds

  • When a monosaccharide reacts with either an alcohol or an amine, a glycosidic bond is formed.
  • O-glycosidic bond: Bond between an anomeric carbon and the OH of an alcohol.
  • N-glycosidic bond: Bond between an anomeric carbon and the N of an amine.
  • Reducing sugar: A sugar that can be oxidized by Cu+2.
  • Methyl-glucopyranoside is not a reducing sugar.

Glycosidic Bonds

  • Monosaccharides react with alcohols and amines.
  • For example, methanol reacts with D-glucose at the anomeric carbon to form a glycoside.

O-Glycosidic Bonds

  • Two forms:
    • methyl α-D-glucopyranoside
    • methyl β-D-glucopyranoside
  • O-glycosidic bond:
    • bond between anomeric carbon & OH of alcohol

N-Glycosidic Bonds

  • Can also react with amine to form an N-glycosidic bond.
  • Important when sugars (ribose) react with purine and pyrimidine bases to form nucleosides, which are components of RNA and DNA.

Methyl-Glucopyranoside

  • Different reactivity to glucose.
  • Glucose reacts with oxidizing agents (Cu+2Cu^{+2}): glucose oxidizes aldehyde → alkanoic acid, and Cu+2Cu^{+2} is reduced to Cu+Cu^+, thus glucose is called a reducing sugar Use tests the presence of reducing sugars.
  • Methyl-glucopyranoside:
    • No such reactivity due to the methyl group joined by an O-glycosidic bond → non-reducing sugar.

Reducing Sugars

  • Can react with other molecules.
  • For example, glucose reacts with free amine groups of hemoglobin.
    • Glycosylated hemoglobin is used to measure the effectiveness of diabetes treatments.
    • Lower glycosylated hemoglobin indicates better treatment for diabetes.

Phosphorylation of Sugars

  • Sugars are often phosphorylated, forming a phospho-ester bond.
  • The first step in glucose breakdown (glycolysis):
    • glucose → glucose-6-phosphate
  • Phosphorylated intermediates, e.g.,:
    • dihydroxyacetone phosphate
    • glyceraldehyde 3-phosphate
  • Phosphorylation gives the glucose a negative charge, trapping glucose in the cell.

Phosphorylated Monosaccharides

  • Examples:
    • α-D-Ribose 5-phosphate
    • Dihydroxyacetone phosphate
    • D-Glyceraldehyde 3-phosphate
    • α-D-Glucose 6-phosphate
    • α-D-Glucose 1-phosphate

Disaccharides

  • For the disaccharides maltose, sucrose, and lactose, describe what monosaccharides and bonds (type of bond, carbons involved, and anomers of the monosaccharides) are present.
  • Which are reducing sugars and which are not? Explain this phenomenon.

Disaccharides

  • Monosaccharides joined by O-glycosidic bonds.
  • For example, maltose:
    • Two D-glucose molecules joined by a glycosidic bond.
    • C4 hydroxyl to C1 carbon.
    • C1 carbon in α-configuration → α-1,4-Glycosidic bond.

Maltose - Disaccharide

  • Hydrolysis product of starch.
  • Hydrolyzed by maltase.

Common Disaccharide - Sucrose

  • Glucose + fructose joined by a glycosidic linkage.
  • Glucose α anomer.
  • Fructose β anomer.
  • Hydrolyzed by sucrase.
  • Not a reducing sugar.

Common Disaccharide - Lactose

  • Galactose + glucose, joined by β-1,4-glycosidic linkage.
  • Hydrolyzed by lactase.

Sucrase, Lactase and Maltase

  • Located on the microvilli of outer epithelial cells lining the small intestine

Polysaccharides

  • What is a polysaccharide?
  • Describe the structure of polysaccharides: glycogen, amylose, amylopectin, cellulose, and chitin.
  • In your answer, describe the monosaccharides that are present in each and how they are bonded together (type of bond, carbons involved, and anomer of the monosaccharide).
  • Which of the polysaccharides can be digested by humans and which cannot?
  • How is cellulose degraded by most animals?

Polysaccharides

  • Multiple monosaccharides joined together.
  • Homo-polysaccharide vs. hetero-polysaccharide, depending on whether the polysaccharide consists of the same sugars joined together or not.

Glycogen

  • Energy storage in muscle & liver.
  • Glucose units joined by α-1,4-glycosidic linkages.
  • α-1,6-glycosidic linkages every 10 glucose residues.

Starch

  1. Amylose:
    • Unbranched polysaccharide.
    • Glucose units joined by α-1,4-glycosidic linkages.
  2. Amylopectin:
    • Branched form, similar to glycogen.
    • Glucose joined mainly by α-1,4-glycosidic bonds.
    • α-1,6-glycosidic linkages approximately every 30 α-1,4-glycosidic linkages.

Cellulose

  • Most abundant organic compound in the biosphere.
  • Polymer of glucose joined by β-1-4-glycosidic linkages.
  • Forms a straight chain.
  • Parallel chains H-bond to each other, forming fibrils.
  • Fibrils have a high tensile strength that allows the formation of plant cell walls.
  • Starch & glycogen exist as helixes.
    • α linkages form the helix.
    • More accessible sugars.
Comparison of Cellulose and Starch/Glycogen
  • Cellulose: β-1,4 linkages, straight chain
  • Starch and Glycogen: α-1,4 linkages, helix/branched

Cellulose Breakdown

  • Cellulase (endo-β-1,4-glucanase) hydrolyzes the β-1,4-glycosidic bond.
  • Enzyme present in most bilateral animals.
  • Discovered in animals from 5 phyla:
    • Arthropoda
      • Termites: wood-feeding invertebrates
      • Cockroaches: wood-eating species
    • Crustaceans such as G. natalis: leaf litter feeding species - ability derived from an aquatic ancestor.
    • Sea urchin
    • Sea squirt
    • Snail
    • Oyster

Chitin

  • Very similar to cellulose.
  • The difference is that the OH group on C2 is replaced by an acetylated amino group (amino sugar N-acetyl glucosamine).
  • Forms fibers.
  • Major component of the exoskeletons of arthropods such as insects & crabs.
  • Next most common polymer after cellulose.