Carbohydrates: Structure, Classification, Reactions, and Glycoconjugates

Mass composition of the human body

Major biochemical categories composition (by weight):
- Water: about 70%
- Inorganic salts: about 5%
- BIOORGANIC SUBSTANCES (contain carbon):
- Proteins: about 15%
- Lipids: about 8%
- Carbohydrates: about 2%
- Nucleic acids: about 2%
BIOINORGANIC SUBSTANCES: substances without carbon
- Water (~70%)
- Inorganic salts (~5%)

Carbohydrates: overview and topics

Topics covered:
- Biological functions of carbohydrates
- Monosaccharides
- Oligosaccharides
- Polysaccharides
- Glycoconjugates

Carbohydrates: general composition and names

Carbohydrates are composed of the elements C, H, and O; commonly called saccharides (meaning “sugars”).
General formulas:
- General empirical form: $Cx(H2O)_y$
- Alternative representation: $(CH2O)n$
Sugars include simple sugars (monosaccharides), polysaccharides (e.g., starch, cellulose), and fibers.

Abundance and plant roles of carbohydrates

Carbohydrates are the most abundant class of bioorganic molecules on Earth.
More than 50% of the carbon in organic compounds is found in carbohydrates (especially in plants).
Carbohydrates constitute ~75% by mass of dry plant material.
Plant uses:
- Structural: cellulose (cell walls)
- Energy reserves: starch (energy storage in plants)

Photosynthesis and respiration: link to energy

Photosynthesis in plants uses CO2, H2O, and solar energy to produce carbohydrates (glucose, etc.).
- Simplified: $ext{CO}2 + ext{H}2 ext{O} + ext{light energy} ightarrow ext{C}6 ext{H}{12} ext{O}6 + ext{O}2$
In respiration, glucose is oxidized to CO2, H2O, and energy.
Carbohydrates link solar energy to chemical bond energy in living organisms.

Biological functions of carbohydrates (summarized)

Store chemical energy: glucose, starch, glycogen
- Energy yield: $1\ ext{g carbohydrate} \rightarrow 4\ \text{kcal}$
- Complex carbohydrates are generally better for dietary energy release.
Precursors and carbon sources for synthesis of other biomolecules (proteins, lipids, nucleic acids).
Structural roles: building blocks for nucleotides (DNA, RNA); structural components alongside proteins and lipids.
Structural/supportive roles in organisms: cellulose in plants; chitin in insects.
Carbohydrates linked to lipids (glycolipids) and to proteins (glycoproteins) participate in cell membranes and in recognition processes (cell–cell recognition, hormone signaling, binding of viruses, etc.).

Glycans, glycosidic linkages, and glycoconjugates

Glycans (saccharides) are polymers of sugars with C, H, O.
General condensation chemistry: formation of glycosidic bonds; hydrolysis reverses the process.
Glycoconjugates include:
- Glycolipids (carbohydrate–lipid conjugates)
- Glycoproteins (carbohydrate–protein conjugates)
- Proteoglycans (protein–carbohydrate conjugates with abundant glycosaminoglycans)
Biological roles include cell recognition, signaling, and immune interactions.

Carbohydrate chemistry: structure and nomenclature basics

Carbohydrates are classified by:
- Number of sugar units (monosaccharides, disaccharides, oligosaccharides, polysaccharides)
- Location of the carbonyl group (aldoses vs ketoses)
- Size of the carbon backbone
Monosaccharides are the simplest; they are the building blocks for larger carbohydrates.

Monosaccharides: properties, nomenclature, and structure

Monosaccharides are the simplest carbohydrates; they cannot be hydrolyzed to smaller sugars.
They typically have molecular formulas that are multiples of CH2O: $ext{(CH}2 ext{O)}n$ with n ≥ 3 in common biologically relevant sugars.
Carbon skeletons range from triose to hexose and beyond (triose, tetrose, pentose, hexose, etc.).
Nomenclature:
- Most monosaccharides end with -ose (e.g., glucose, ribose).
- Triose sugars glyceraldehyde and dihydroxyacetone are exceptions in naming (glyceraldehyde ends with -ose though it is a triose).
- Ketose forms are often indicated with suffix -ulose (e.g., ribulose).

Classification of monosaccharides

Based on carbonyl group location:
- Aldoses: aldehyde functional group at one end (C1).
- Ketoses: ketone functional group, usually at C2.
Based on carbon count: triose (C3), tetrose (C4), pentose (C5), hexose (C6), etc.
Examples:
- Aldoses: glyceraldehyde (C3, aldose), ribose (C5, aldose), glucose/galactose/mannose (C6, aldohexoses)
- Ketoses: dihydroxyacetone (C3, ketose), ribulose/xylulose (C5, ketoses), fructose (C6, ketohexose)

Stereochemistry and chiral centers in monosaccharides

Enantiomers: non-superimposable mirror images; D- and L- forms are determined by the configuration at the highest-numbered chiral center (penultimate carbon).
D-sugars have the hydroxyl group on the right at the highest-numbered chiral center in Fischer projection; L-sugars have it on the left.
Chiral center (asymmetric carbon): a carbon attached to four different groups.
Epimers: stereoisomers that differ in configuration at exactly one chiral center (e.g., glucose vs galactose differ at C4; glucose vs mannose differ at C2).
Enantiomer pairs: D- and L- forms; e.g., D-glucose vs L-glucose.
D and L nomenclature sometimes maps to R/S (D ≈ R for common sugars; L ≈ S), but for sugars the D/L convention is used more frequently.

Fischer vs Haworth projections; mutarotation; anomeric carbon

Fischer projection: a two-dimensional representation with vertical bonds oriented away from the viewer and horizontal bonds toward the viewer.
Haworth projection: cyclic representation; ring forms (pyranose six-membered rings; or furanose five-membered rings) are drawn with the ring oxygen and substituents.
Rule for translating Fischer to Haworth:
- Any -OH group to the right in a Fischer projection points down in the Haworth projection; any -OH to the left points up.
Anomeric carbon: the carbon that was carbonyl carbon in the open-chain form (C1 in aldoses; C2 in ketoses) becomes the anomeric center in the cyclic hemiacetal/hemiketal form. Forms are designated α or β depending on the orientation of the substituent at the anomeric carbon relative to the ring.
Mutarotation: interconversion between α and β anomers via the open-chain form in aqueous solution; example: D-glucose in water equilibrates to approx. 63% β and 37% α.
Pyranose vs furanose: six-membered (pyranose) rings vs five-membered (furanose) rings; chair conformation is usually more stable than boat due to steric hindrance.

Important monosaccharides (highlights)

Glucose: most abundant in nature; nutritionally important; six-membered ring (α/β anomers); D isomer predominates in biology.
Fructose: ketohexose; sweetest natural sugar; exists as a five-membered furanose ring in solution.
Galactose: epimer of glucose at C4; important in glycoproteins and blood group determinants.
Ribose: aldopentose; backbone for RNA.
Glyceraldehyde: simplest aldose; chiral center; used to define D/L sugar configurations.
Other common monosaccharides include arabinose, xylose, and others mentioned in curricular slides.

Monosaccharide derivatives

Amino sugars: substitution of -OH at C-2 by an amino group, often acetylated (e.g., N-acetylglucosamine, GlcNAc).
Deoxy sugars: replacement of -OH by H at particular positions (e.g., fucose, rhamnose).
Phosphorylated sugars: phosphate esters (e.g., glucose-6-phosphate) formed via condensation with phosphate; important in metabolism and enzyme reactions (e.g., hexokinase forming glucose-6-phosphate).
Aldonic acids, aldaric acids, and alduronic acids: products of oxidation at terminal carbon (aldose oxidation) or both ends (aldaric) or oxidation at the terminal carbon followed by enzymatic conversion (alduronic).
Sugar alcohols (sugar alcohols like sorbitol/glucitol) result from reduction of the carbonyl group.

Reactions of monosaccharides (overview)

Five important reactions (illustrated using glucose as model):

Oxidation to acidic sugars:
- Aldonic acids (weak oxidizing agents): e.g., glucose → gluconic acid
- Aldaric acids (strong oxidants): oxidation at both ends may yield saccharic-like acids
- Alduronic acids (enzymatic oxidation at the terminal carbon): e.g., glucuronic acid
Reduction to sugar alcohols (e.g., glucose to sorbitol/glucitol)
Phosphate ester formation: formation of sugar phosphates (e.g., glucose-6-phosphate) via reaction with ATP in metabolism; enzyme-catalyzed processes (e.g., hexokinase) depicted.
Glycoside formation (glycosidic bonds) with alcohols to form acetals (glycosides).
Other derivative formations: amino sugars, and reactions that lead to glycoside formation.

Reducing vs non-reducing sugars (disaccharides and monosaccharides)

Reducing sugars: possess a free anomeric carbon that can open to form an aldehyde or participate in redox chemistry; e.g., lactose, maltose, glucose (in free form).
Non-reducing sugars: both anomeric carbons are involved in glycosidic bonds, and the sugar cannot be oxidized directly under mild conditions; e.g., sucrose.

Disaccharides: structures and properties

Disaccharides are formed from two monosaccharides via a glycosidic bond; the linkage can be α or β and can be 1→4, 1→2, 1→1, etc.
Common disaccharides:
- Maltose: glucose–glucose with an α(1→4) glycosidic bond; reducing sugar due to one hemiacetal center.
- Cellobiose: glucose–glucose with a β(1→4) glycosidic bond; reducing sugar.
- Lactose: galactose–glucose with a β(1→4) glycosidic bond; reducing sugar.
- Sucrose: glucose–fructose with an α(1→2) glycosidic bond; non-reducing sugar (both anomeric carbons involved in glycosidic bonds).
Nomenclature example: α-D-Glucopyranosyl-(1→4)-α-D-glucopyranose (maltose).
Non-reducing vs reducing: Sucrose is non-reducing because neither anomeric carbon is free.
Hydrolysis of disaccharides releases their constituent monosaccharides; hydrolysis of lactose by lactase: lactose intolerance occurs in individuals with low lactase activity; lactase supplements can aid digestion.
Invert sugar: hydrolysis of sucrose to glucose and fructose; rotation of plane-polarized light changes direction due to different optical rotations of glucose and fructose; the mixture is called invert sugar and has a net rotation of approximately $-0.39\times 10^{1}$ degrees (historical value varies with conditions).

Practice: disaccharide properties and hydrolysis

Hydrolysis of maltose, lactose, and sucrose yields their monosaccharide constituents.
The glycosidic bond is the site of hydrolysis in disaccharides; water donates H to one sugar and OH to the other during hydrolysis.

Oligosaccharides

Oligosaccharides contain 3–10 monosaccharide units.
They are rarely found as free oligosaccharides in biochemical systems; more commonly attached to proteins or lipids as glycoconjugates.
Examples found in foods and biology include raffinose (trisaccharide) and stachyose (tetrasaccharide).
Roles include cell–cell recognition, adhesion, and signaling; often part of glycoconjugates on cell surfaces.
In plant and animal tissues, oligosaccharides contribute to various biological processes including immune response and development.

Glycoconjugates and glycans

Glycoconjugates: informational carbohydrates covalently joined to proteins or lipids; three main types:
- Glycolipids (carbohydrate–lipid conjugates)
- Glycoproteins (carbohydrates covalently attached to proteins)
- Proteoglycans (protein core with many glycosaminoglycan chains)
Glycoconjugates play essential roles in cell recognition, signaling, and host defense.
Blood group antigens are examples of glycoconjugate carbohydrate determinants on erythrocyte surfaces.

Glycoconjugates: glycoproteins and blood groups

Glycoproteins: proteins with covalently attached oligosaccharide chains; oligosaccharides are branched, often unsulfated, and provide antigenic determinants.
Blood group determinants (ABO): terminal sugars at the nonreducing end of the glycoprotein on red blood cells determine the ABO blood type:
- Type A: N-acetylgalactosamine (GalNAc) at the nonreducing end.
- Type B: D-galactose at the nonreducing end.
- Type AB: both GalNAc and Gal are present.
- Type O: neither GalNAc nor Gal present; no terminal sugar.
Universal donors/recipients: Type O is the universal donor; Type AB is the universal recipient.

Glycosaminoglycans (GAGs) and acidic polysaccharides

GAGs are acidic, negatively charged polysaccharides that are typically heteropolysaccharides composed of repeating disaccharide units that include an amino sugar and either a uronic acid or a sulfated sugar.
Major examples and roles:
- Hyaluronic acid: repeating disaccharide of β-D-glucuronic acid and N-acetyl-D-glucosamine in a β-(1→4) linkage, with alternating β-(1→3) and β-(1→4) linkages; functions as a lubricant in joints and vitreous humor; extremely viscous.
- Chondroitin sulfate: repeating units of D-glucuronic acid and D-glucosamine sulfate; structural role in cartilage, bone, and cornea.
- Dermatan sulfate: contains iduronate and N-sulfated polysaccharide units; contributes to skin pliability and blood vessel integrity.
- Keratan sulfate: sulfated sugar chains (keratan) found in cornea, cartilage, bone; important in structural tissues.
- Heparin: highly sulfated GAG; anticoagulant that inhibits blood clot formation; used in open-heart surgery.
- Dermatan sulfate, keratan sulfate, and heparin are all acidic polysaccharides with diverse biological roles.
- Alginic acid: from brown seaweeds; composed of β-D-muanuronic and α-L-guluronic acid units; used as a cell wall constituent in algae and as a gelling agent in foods.

Polysaccharides: general concepts and classifications

Polysaccharides are long polymers of monosaccharides linked by glycosidic bonds.
Important parameters distinguishing polysaccharides:
1) Identity of repeating monosaccharide units (homopolysaccharides vs heteropolysaccharides)
2) Polymer length
3) Type of glycosidic linkage (α or β; 1→4, 1→6, etc.)
4) Degree of branching
Types:
- Homopolysaccharides: contain a single type of monosaccharide (e.g., starch, glycogen, cellulose).
- Heteropolysaccharides: contain two or more different monosaccharides (e.g., glycosaminoglycans, glycoproteins, proteoglycans).

Starch, glycogen, and cellulose (examples of major polysaccharides)

Starch (Homosaccharide): polymer of glucose, general formula $ext{(C}6 ext{H}{10} ext{O}5)n$ ; storage polysaccharide in plants.
- Composed of two components:
- Amylose: mostly unbranched; α-1,4 linkages; forms a helical structure; about 15–20% of starch.
- Amylopectin: highly branched; α-1,6 linkages at branch points; branches approx every 25–30 glucose units; makes up 80–85% of starch.
- Iodine test: amylose forms a dark blue complex; amylopectin shows purple/brown (less intense).
Glycogen (Homosaccharide): storage polysaccharide in animals; highly branched glucose polymer with α-1,4 backbones and α-1,6 branches every 8–12 glucose units; liver and muscle store glycogen.
Cellulose (Homosaccharide): structural component of plant cell walls; linear β-(1→4) linked glucose units; forms β-sheet hydrogen-bonded fibers; humans cannot digest cellulose due to lack of β-(1→4) glycosidases; dietary fiber.
Comparison highlights: Amylose (unbranched; α-1,4); Amylopectin (branched; α-1,6); Glycogen (very branched); Cellulose (β-1,4; not digestible by humans).

Structural features and conformations of polysaccharides

Conformations: pyranose (six-membered) and furanose (five-membered) rings common for hexoses and pentoses.
Anomeric carbon: C1 in aldoses; C2 in ketoses. α vs β forms depend on the orientation of the substituent at the anomeric carbon.
Chair vs boat conformations: chair is generally most stable due to reduced steric hindrance; bulky substituents prefer equatorial positions.

Cyclic structures and Haworth projections

In aqueous solution, monosaccharides with 5 or more carbon atoms predominantly form cyclic (ring) hemiacetals or hemiketals.
Haworth projections are the standard way to depict cyclic forms.
Rule for converting Fischer to Haworth: rightward -OH groups in Fischer project down in Haworth; leftward -OH groups project up.
Examples: D-glucose forms α-D-glucopyranose and β-D-glucopyranose; open-chain form is in equilibrium with cyclic forms.
Anomeric carbon and mutarotation govern the interconversion among α and β forms.

Important specific cyclized forms

D-Glucose: forms a six-membered pyranose ring; α- and β- anomers exist; mutarotation occurs in solution.
D-Fructose: commonly forms a five-membered furanose ring (in open-chain form, ketohexose).

Stereochemistry: enantiomers, diastereomers, epimers

Enantiomers: non-superimposable mirror images (e.g., D-glucose vs L-glucose).
Diastereomers: stereoisomers that are not mirror images (e.g., erythrose vs threose; A and B, C and D in lecture slides).
Epimers: diastereomers that differ at exactly one chiral center (e.g., glucose vs galactose differ at C4; glucose vs mannose differ at C2).
Relationship to biological activity: e.g., epinephrine enantiomers show different receptor binding; natural sugars are mostly D isomers; many biologically relevant amino acids are L isomers.
Optical activity: enantiomers rotate plane-polarized light; dextrorotatory (+) rotates clockwise; levorotatory (-) rotates counterclockwise.
D vs L and R vs S correlations: for monosaccharides the common convention uses D/L; R/S is a separate stereochemical descriptor.

Enantiomers, diastereomers, and conformational isomerism

Enantiomers are nonsuperimposable mirror images; key concept in biological recognition.
Diastereomers include epimers and cis/trans isomers; differ in configuration at one or more chiral centers but are not mirror images.
Cis/trans isomerism can arise in ring systems or restricted rotation around bonds (e.g., some glycosidic linkages or cyclic systems).

Practical aspects: mutarotation, epimers, and biological relevance

Mutarotation demonstrates that anomeric configuration can interconvert in solution (open-chain form allows re-equilibration between α and β forms).
Epimers and diastereomers illustrate how small structural changes can markedly affect biological properties and recognition in metabolic pathways.
In biology, D-sugars are much more common in metabolism and nutrition; many plant and dietary carbohydrates are D-stereoisomers.

Reactions and chemical utilities of monosaccharides (focus on glucose)

Oxidation reactions yield acidic sugars:
- Aldonic acids (weak oxidizers): glucose → gluconic acid
- Aldaric acids (strong oxidizers): glucose → glucaric/gluconic-type products
- Alduronic acids (enzymatic oxidation at the terminal C): glucose → glucuronic acid
Reduction of carbonyl groups yields sugar alcohols (e.g., glucose → sorbitol/glucitol).
Phosphate ester formation: sugars form esters with phosphate groups (e.g., glucose-6-phosphate) essential in metabolism; catalyzed by enzymes like hexokinase with ATP.
Glycoside formation: cyclic hemiacetals react with alcohols to form acetals (glycosides). Example: α-D-glucopyranoside derivatives.
Derivatives of monosaccharides: amino sugars (e.g., N-acetylglucosamine), deoxy sugars (e.g., fucose, rhamnose), and sugar phosphates.

Reducing sugars and hydrolysis concepts

Reducing sugars: contain a free aldehyde (or can form one via ring opening) and can be oxidized; examples include glucose, maltose, lactose.
Non-reducing sugars: glycosidic bonds involve both anomeric carbons; e.g., sucrose.
Hydrolysis concepts: disaccharides hydrolyze to monosaccharides; water supplies H and OH across the glycosidic linkage during hydrolysis.

Specific disaccharides and their properties

Maltose: glucose–glucose α(1→4); reducing sugar (one hemiacetal is free).
Cellobiose: glucose–glucose β(1→4); reducing sugar.
Lactose: galactose–glucose β(1→4); reducing sugar.
Sucrose: glucose–fructose α(1→2); non-reducing sugar (both anomeric carbons involved in glycosidic bond).
Hydrolysis products and the concept of invert sugar: hydrolysis of sucrose yields glucose and fructose; changes optical rotation due to different rotations of glucose and fructose.

Sucrose hydrolysis and dietary relevance

Sucrose hydrolyzed by sucrase (invertase) in the small intestine to glucose and fructose for absorption.
Invert sugar formulation results from hydrolysis of sucrose; mixture rotation depends on relative rotations of glucose and fructose.

Oligosaccharides: biology and nutrition

Oligosaccharides are typically not found as isolated species in biology; they usually exist as parts of glycoconjugates.
They play critical roles in cell recognition, cell signaling, and adhesion; examples include raffinose and stachyose found in beans and onions.
They can be linked to proteins or lipids to form glycoconjugates with functional roles in development, immune response, and tissue organization.

Polysaccharides: detailed examples and properties

Starch: storage polysaccharide in plants; general formula $ext{(C}6 ext{H}{10} ext{O}5)n$ ; composed of amylose (unbranched, α-1,4) and amylopectin (branched, α-1,6 at branching points every ~25–30 glucose units).
- Amylose forms a helical structure; amylopectin provides branched structure and increased solubility.
Glycogen: storage polysaccharide in animals; highly branched glucose polymer; branching every 8–12 glucose units; stored in liver and muscles; more highly branched than amylopectin.
Cellulose: structural polysaccharide in plants; β-(1→4) linked glucose units; forms extended hydrogen-bonded fibers; human enzymes cannot hydrolyze β-(1→4) linkages; cellulose is dietary fiber.
Dextran: bacterial/yeast polysaccharide with (α1→6) linked glucose backbones and various α1→3 branches; used in chromatography (Sephadex) and dental plaque formation.
Carrageenan: sulfated polysaccharide from red algae; consists of alternating α- and β-galactose linkages; used as a gelling/thickening agent.
Alginic acid: composed of β-D-mannuronic acid and α-L-guluronic acid units; derived from brown algae; used as a thickener and stabilizer in foods.
Chitin and chitosan:
- Chitin: linear β-(1→4) polysaccharide of N-acetyl-D-glucosamine (NAG); rigid exoskeletons in crustaceans and cell walls in fungi.
- Chitosan: derivative of chitin; random distribution of β-(1→4)-linked D-glucosamine and N-acetyl-D-glucosamine; produced by deacetylation of chitin.

Glycoscoconjugates: overview and functional implications

Glycolipids: membrane lipids with oligosaccharide head groups; involved in cell recognition and signaling.
Glycoproteins: proteins with covalently attached oligosaccharides; important in immune response, antigen recognition, and blood group determinants.
Proteoglycans: proteins heavily substituted with glycosaminoglycans; structural and signaling roles in the extracellular matrix.
Blood type determinants (ABO) are examples of glycoconjugate markers on red blood cells; terminal sugar residues determine the blood type and influence antigen–antibody interactions.

Glycoconjugates in human biology and medicine

Blood type system (ABO):
- A: terminal GalNAc (N-acetylgalactosamine)
- B: terminal Gal (galactose)
- AB: both GalNAc and Gal present
- O: neither GalNAc nor Gal at the nonreducing end
Implications for transfusion compatibility: matching A, B, AB, O types with corresponding antibodies.
Glycoproteins and immune recognition: antibodies (e.g., immunoglobulins) are glycoproteins; glycan portions determine antigenic determinants and binding properties.

Dietary carbohydrates: considerations and physiology

Dietary carbohydrate categories:
- Simple carbohydrates: dietary monosaccharides or disaccharides
- Natural sugars: present in whole foods
- Refined sugars: isolated from plant sources; often termed empty calories due to limited nutrients beyond energy
- Complex carbohydrates: dietary polysaccharides (starches, glycogen, fibers)
Fiber sources: whole grains, fruits, vegetables; recommended daily intake ~25–35 g (varies by guidelines and individual needs).
Health implications of fiber and carbohydrate quality: reduces absorption of dietary fats, lowers cholesterol, and may support digestive health; helps regulate digestion and toxin removal.

Quick reference: key equations and constants

Photosynthesis (simplified):
- Simplified overall: $6\ CO2 + 6\ H2O + \text{light energy} \rightarrow C6H{12}O6 + 6\ O2$
Energy yield from carbohydrates: $1\ ext{g carbohydrate} \rightarrow 4\ \text{kcal}$
Carbohydrate general formula: $Cx(H2O)y \quad \text{or} \quad (CH2O)_n$
Disaccharide glycosidic bonds: examples include maltose (α(1→4)), lactose (β(1→4)), sucrose (α(1→2))
Monosaccharide derivatives:
- N-Acetylglucosamine (GlcNAc) is a key amino sugar derivative.
- Fucose and rhamnose are deoxy sugars.

Quick practice and takeaway points

Identify whether a given disaccharide is reducing or non-reducing based on the presence of a free anomeric carbon.
Distinguish aldoses vs ketoses by carbonyl location; recognize common examples: glucose (aldose, C6), fructose (ketose, C6).
Recognize that starch and glycogen are storage polysaccharides in plants and animals, respectively; cellulose is structural and indigestible by humans.
Understand that glycosylation patterns (glycoproteins, glycolipids, GAGs) contribute to cell recognition, signaling, and immune interactions.
Interpret blood type antigens as terminal carbohydrate determinants on erythrocyte surfaces.

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