Chapter 18: Carbohydrates — Comprehensive Study Notes
18.1 Biochemistry—An Overview
Biochemistry: study of chemical substances in living organisms and their interactions.
Biochemistry as a living-system science: cells synthesize life-needed molecules; reactions sustain life.
Massive growth in knowledge over the late 20th and early 21st centuries.
Biochemical substances are divided into two groups:
Bioinorganic substances: water and inorganic salts.
Bioorganic substances: carbohydrates, lipids, proteins, nucleic acids.
Body mass composition (approximate; Figure 18.1):
Water: ~70%
Inorganic salts: ~5%
Proteins: ~15%
Carbohydrates: ~2%
Nucleic acids: ~2%
Lipids (as bioorganic): ~8%
Carbohydrates are the most abundant class of bioorganic molecules on Earth (particularly in plants; ~75% by mass of dry plant material).
Photosynthesis in plants: CO₂ + H₂O + light → carbohydrates; chlorophyll is the energy-capture pigment.
Roles of carbohydrates in humans and plants:
Energy source via oxidation
Short-term energy storage as glycogen
Provide carbon skeletons for synthesis of other biomolecules (proteins, lipids, nucleic acids)
Structural roles in DNA/RNA backbones and cell membranes (glycolipids)
Involvement in cell–cell and cell–molecule recognition via glycoproteins/glycolipids
Chapter structure (biochapter): focus on carbohydrates first, followed by metabolism of carbohydrates, lipids, and proteins.
18.2 Occurrence and Functions of Carbohydrates
Carbohydrates are the most abundant bioorganic molecules on Earth; in humans, they are a smaller fraction of total body mass but extremely important biologically.
Key plant role: photosynthesis produces carbohydrates (green plants); major plant carbohydrate resources are cellulose (structural) and starch (energy reserve).
Functions in humans (listed):
Carbohydrate oxidation provides energy.
Carbohydrate storage as glycogen provides short-term energy reserve.
Carbohydrates supply carbon atoms for synthesis of proteins, lipids, nucleic acids.
Carbohydrates form part of DNA/RNA structural framework.
Carbohydrates linked to lipids (glycolipids) are components of cell membranes.
Carbohydrates linked to proteins (glycoproteins) participate in cell–cell and cell–molecule recognition.
Figure 18.1 (mass composition) and Figure 18.2 (plant matter) illustrate distribution and photosynthetic basis of carbohydrate abundance.
Important note: despite their ubiquity, carbohydrates are a diverse class with multiple subtypes and roles, often interacting with each other within cells.
18.3 Classification of Carbohydrates
General carbohydrate formula concept: simple carbohydrates have empirical formula general form , historically written as (the view is not strictly correct, but the term “carbohydrate” persists).
A carbohydrate is a polyhydroxy aldehyde, a polyhydroxy ketone, or a compound that yields polyhydroxy aldehydes/ketones upon hydrolysis.
Glucose: polyhydroxy aldehyde.
Fructose: polyhydroxy ketone.
Structure and functionality: large numbers of functional groups; interactions among carbohydrates lead to larger biomolecular assemblies.
Classification by size:
Monosaccharides: single polyhydroxy aldehyde/ketone unit; cannot be hydrolyzed to simpler carbs.
Disaccharides: two monosaccharide units covalently bonded.
Oligosaccharides: 3–10 monosaccharide units.
Polysaccharides: many monosaccharide units covalently bonded; may be branched or unbranched.
Solubility and physical characteristics: monosaccharides are water-soluble; many disaccharides are crystalline and water-soluble; polysaccharides are generally not water-soluble as individual molecules, forming colloidal suspensions.
Major plant and animal carbohydrates in everyday life: cotton/wood (cellulose), starch (amylose/amylopectin), glycogen (animal storage). The term “sugar” extends to monosaccharides and many disaccharides.
18.4 Chirality: Handedness in Molecules
Handedness (chirality) is a property where molecules exist as two non-superimposable mirror images.
Chiral center (also called a stereogenic center): a carbon (usually) with four different groups bonded in a tetrahedral geometry. Molecules with a chiral center are chiral; their mirror images are non-superimposable.
Achiral molecules: mirror images are superimposable.
Simple example: bromochloroiodomethane (CHBrClIH) has four different substituents and is chiral; glyceraldehyde is another classic example with four different substituents around its chiral carbon.
In rings, chirality can also arise in cyclic structures when two halves of a ring are not equivalent (e.g., substituted cycloalkanes).
Notation: chiral centers are often marked with an asterisk (*).
Guidelines for identifying chiral centers (brief):
A carbon involved in a multiple bond (C=C, C≡C) cannot be a chiral center.
A carbon with two identical substituents cannot be a chiral center.
In rings, a carbon can be a chiral center if the two substituents and the two ring halves are different.
Examples and illustrations show three- and four-substituent chiral centers; ring systems can also be chiral depending on substituent differences.
Importance: chirality underlies stereochemistry in biochemistry and affects interactions with enzymes and receptors.
18.5 Stereoisomerism: Enantiomers and Diastereomers
Stereoisomers share the same connectivity but differ in spatial arrangement.
Enantiomers: non-superimposable mirror images; each has opposite optical rotation and often different biological activity.
Diastereomers: stereoisomers that are not mirror images; may have different physical properties.
Key structural features generating stereoisomerism:
Presence of chiral centers
Structural rigidity that restricts rotation (cis–trans isomerism is a related form of stereoisomerism)
Within monosaccharides (and others) with multiple chiral centers, a single structure can have both enantiomeric and diastereomeric relationships with other stereoisomers; epimers are diastereomers differing at exactly one chiral center.
Summary diagram (conceptual): enantiomers are mirror-image pairs; diastereomers are not mirror images; constitutional isomers differ in connectivity.
The Greek-derived terms: enantiomer from enantios; diastereomer from diastereo.
Practical implication: enantiomers often have identical physical properties (except for optical rotation) but can interact differently with chiral environments (e.g., enzymes, receptors) and thus have different biological activities.
18.6 Designating Handedness Using Fischer Projection Formulas
Fischer projection: a two-dimensional representation clarifying chirality at each chiral center.
Conventions:
The carbon chain is vertical; highest-priority carbonyl-bearing carbon sits at the top.
Groups projecting into the page are shown along the vertical axis; groups projecting out are on the horizontal axis.
Vertical bonds denote substituents going back (into the page); horizontal bonds denote substituents coming out of the page.
In monosaccharides, the typical convention places the carbon chain vertically with the carbonyl group at the top.
D/L designation for monosaccharides: determined by the configuration at the highest-numbered chiral center (farthest from the carbonyl group).
In glyceraldehyde, the chiral center determines D vs L by the position of the OH group.
The D-enantiomer has the chiral OH on the right in the Fischer projection; the L-enantiomer has it on the left.
Reversing all horizontal substituents at every chiral center generates the opposite enantiomer.
For monosaccharides with multiple chiral centers, D/L designations extend by considering the highest-numbered chiral center; other centers are designated by the name (e.g., D-erythrose vs D-threose, etc.).
The D/L system is extended to more complex monosaccharides: the highest-numbered chiral center determines the overall D/L, with additional stereochemical descriptors (erythro/threo) used for multiple centers.
Practical exercise examples illustrate converting between Fischer projections and enantiomeric pairs.
18.7 Properties of Enantiomers
Constitutional isomers differ in connectivity; stereoisomers (enantiomers and diastereomers) share connectivity but differ in spatial arrangement.
Enantiomers: identical in most physical properties (boiling/melting points, density) but differ in:
1) Interaction with plane-polarized light (optical rotation).
2) Interactions with other chiral substances (e.g., receptors, enzymes).Optically active: chiral compounds rotate plane-polarized light; the rotation can be clockwise (dextrorotatory, +) or counterclockwise (levorotatory, −).
Polarimetry: instrument (polarimeter) measures rotation; enantiomers in equal molar amounts rotate light by equal magnitude in opposite directions.
The D/L handedness and the direction of optical rotation are not inherently linked.
Biological implications: enantiomers interact differently with chiral biological systems; examples include:
Taste receptors differentiate enantiomers (spearmint vs caraway flavors; carvone enantiomers).
Hormone epinephrine: D-epinephrine elicits a much stronger response than L-epinephrine due to receptor binding specificity.
The “Chemistry at a Glance” summary (in the book) consolidates how enantiomers, diastereomers, and constitutional isomers relate to stereochemistry concepts.
Optical activity is a defining feature of chiral compounds; achiral molecules are optically inactive.
18.8 Classifying Monosaccharides as D or L Enantiomers
Monosaccharides are classified by carbon count (triose, tetrose, pentose, hexose) and by carbonyl type (aldose vs ketose).
Aldoses contain an aldehyde group (polyhydroxy aldehydes); ketoses contain a ketone group (polyhydroxy ketones).
Natural sugars in organisms are almost exclusively D isomers (D-configuration) with a few exceptions.
The highest-numbered chiral center determines D or L configuration.
Cyclic forms (glucose, fructose, etc.) form via intramolecular hemiacetal formation and yield anomers (alpha and beta).
D- and L- forms are often named explicitly (e.g., D-glucose, L-glucose) and naming is extended to more complex monosaccharides via Fischer projections and Haworth projections.
18.9 Biochemically Important Monosaccharides
Six key monosaccharides widely important in biology:
D-glyceraldehyde (aldose, triose) – chiral; reference point for sugars.
D-dihydroxyacetone (non-chiral triose).
D-glucose (aldohexose) – most abundant in nature; primary energy source in humans (also called dextrose or blood sugar).
D-galactose (aldohexose) – epimer of glucose at C-4; component of lactose.
D-fructose ( ketohexose ) – keto sugar; most sweet; rotates plane-polarized light to the left (levulose).
D-ribose (aldopentose) – component of RNA; essential in nucleic acid chemistry; 2-deoxy-D-ribose is critical for DNA.
Structural features: Fischer projections and common names for aldoses and ketoses of 3–6 carbons; D- is predominant in nature; L- is less common in biology.
D-glucose and D-galactose are epimers at C-4; D-fructose is a keto sugar with a different open-chain structure but shares most stereochemical features with glucose from C-3 to C-6.
D-ribose is a pentose and a key nucleoside sugar; 2-deoxy-D-ribose is used in DNA.
18.10 Cyclic Forms of Monosaccharides
Open-chain monosaccharides (acyclic) are in equilibrium with cyclic hemiacetals/hemiketals for five or more carbon atoms.
Cyclization occurs via intramolecular reaction between the carbonyl group and a hydroxyl group (usually at C-5 for hexoses, C-4 for aldopentoses).
For D-glucose, cyclization yields a six-membered ring (pyranose). The ring can exist in two anomeric forms: α and β. The anomeric carbon is C-1 in aldoses.
For D-fructose, cyclization typically yields a five-membered ring (furanose).
In aqueous solution of D-glucose, equilibrium distribution: approximately 63% β-D-glucose, 37% α-D-glucose, <0.01% open-chain.
Anomers differ only in the orientation of the substituents around the anomeric carbon (C-1 in aldoses). The α form has the anomeric OH opposite to the CH₂OH substituent; the β form has it on the same side.
The anomeric carbon in cyclic monosaccharides is the hemiacetal carbon; cyclization creates this new stereogenic center, generating two stereoisomers (α and β).
D- and L- forms of the same sugar interconvert only at the chiral centers; ring closure does not change D/L designation.
18.11 Haworth Projection Formulas
Haworth projections: two-dimensional representations of cyclic monosaccharides.
Rings: six-membered (pyranose) or five-membered (furanose).
In Haworth projections, the ring oxygen is at the upper-right (six-membered) or at the top (five-membered).
The D or L form is determined by the position of the terminal CH₂OH group at the highest-numbered stereocenter: in the D form, CH₂OH is above the ring; in L form, CH₂OH is below.
The orientation of OH groups in the Haworth projection is determined by their positions in the corresponding Fischer projection (right in Fischer → down in Haworth; left in Fischer → up in Haworth).
Examples: convert between Fischer and Haworth for common sugars (e.g., D-mannose, D-glucose, D-galactose).
Anomeric configuration (α vs β) is preserved in Haworth as well: α means OH on the anomeric carbon is trans to the CH₂OH group; β means cis.
18.12 Reactions of Monosaccharides
Five important reactions: oxidation to acidic sugars, reduction to sugar alcohols, glycoside formation, phosphate ester formation, and amino sugar formation.
Oxidation to acidic sugars:
Aldoses can be oxidized at the aldehyde end to form aldonic acids (e.g., glucose → gluconic acid).
Example: Tollens’ or Benedict’s solutions detect reducing sugars; aldoses are reducing agents; with alkaline conditions, some ketoses rearrange to aldoses and become reducing.
Polyhydroxy dicarboxylic acids (aldaric acids) can form when both ends are oxidized (e.g., glucose → glucaric acid).
Enzymatic oxidation can yield uronic acids (e.g., D-glucuronic acid).
Reduction to sugar alcohols:
Carbonyl group reduced to hydroxyl group (hydrogen donor), producing sugar alcohols (e.g., D-glucose → D-sorbitol, aka D-glucitol).
Glycoside formation (glycosidic linkage formation):
Hemiacetal (cyclic) carbon reacts with an alcohol (R–OH) to form a glycoside (acetal) with the release of water.
Monosaccharide glycosides are named by listing the attached alkyl/aryl group followed by the sugar name (e.g., methyl-D-glucoside).
Phosphate ester formation:
Monosaccharides can be esterified with phosphate groups (e.g., glucose-1-phosphate, glucose-6-phosphate).
These esters play essential roles in metabolism and enzyme-catalyzed reactions.
Amino sugar formation:
Replacement of a ring hydroxyl group with amino group at C-2 yields amino sugars (e.g., glucosamine, galactosamine, mannosamine); N-acetyl derivatives are common in nature.
Special notes:
Glycosidic linkages are carbon–oxygen–carbon bonds; hydrolysis can reverse glycoside formation.
Some sugars form N-acetyl derivatives that are key components of polysaccharides (e.g., chitin).
18.13 Disaccharides
A disaccharide forms when two monosaccharides join via a glycosidic linkage, with one unit acting as a hemiacetal and the other as an alcohol.
Maltose: two D-glucose units linked by an α(1→4) glycosidic linkage; maltose is a reducing sugar (the right glucose unit has a hemiacetal carbon at C-1).
Maltose exists in α- and β- forms in solution; β form is dominant in solid state.
Hydrolysis yields two molecules of D-glucose.
Cellobiose: two glucose units linked by a β(1→4) linkage; also a reducing sugar; produced as an intermediate in cellulose digestion.
Lactose: composed of β-D-galactose and D-glucose linked by β(1→4); reducing sugar due to the glucose hemiacetal at C-1; major sugar in milk; lactose is hydrolyzed by lactase to galactose and glucose.
Sucrose: glucose and fructose linked by α,β(1→2) linkage; nonreducing (both anomeric carbons are involved in the linkage).
Hydrolysis consequences: maltose/cellobiose/lactose hydrolyze to glucose or galactose + glucose; sucrose hydrolyzes to glucose + fructose (invert sugar).
18.14 Oligosaccharides
Definition: 3–10 monosaccharide units; often present in complex biomolecules, associated with proteins or lipids.
Raffinose (trisaccharide): components are galactose, glucose, and fructose; linkages include α(1→6) and α/β(1→2) types.
Stachyose (tetrasaccharide): one extra galactose unit beyond raffinose; similar linkage variety.
Humans lack enzymes to digest raffinose and stachyose; they pass undigested to the large intestine where bacteria metabolize them, producing gas.
Beano and related products contain the enzyme α-galactosidase to help digest these oligosaccharides.
Blood types: blood-group antigens are oligosaccharide markers on red blood cell membranes; different blood types arise from different terminal sugars in these markers (A, B, AB, O).
Solanine: a potato toxin whose structure includes a trisaccharide moiety attached to a multi-ring alkaloid; L-rhamnose (6-deoxy-L-mannose) is an example of the rare monosaccharide in such oligosaccharide contexts.
18.15 General Characteristics of Polysaccharides
Polysaccharides: polymers of monosaccharides; several subtypes distinguished by repeating units, chain length, glycosidic linkages, and branching.
Homopolysaccharides: contain a single type of monosaccharide repeating unit (e.g., starch, glycogen, cellulose, chitin).
Heteropolysaccharides: contain two or more different monosaccharide units (e.g., hyaluronic acid, heparin).
Chain length: can range from a few hundred to over a million monomer units.
Glycosidic linkages: multiple types; arrangements include (1→4), (1→6), (1→2), etc.
Branching: polysaccharides can be linear or highly branched; branching affects physical properties and digestibility.
Polysaccharides generally are not sweet and do not test positive with Tollens/Benedict’s reagents; they form viscosity-rich colloidal solutions.
In nutrition, monosaccharides and disaccharides are considered simple carbohydrates; polysaccharides are complex carbohydrates.
18.16 Storage Polysaccharides
Storage polysaccharides store monosaccharides as energy sources; reduce osmotic pressure by concentrating many sugars into a single molecule.
Starch (plants): storage polysaccharide; consists of two components:
Amylose: mostly linear (α(1→4) linkages).
Amylopectin: branched (α(1→4) linear and α(1→6) branch points approximately every 25–30 glucose units).
Total starch often contains about 15–20% amylose and 80–85% amylopectin.
Amylose is unbranched with α(1→4) linkages; amylopectin is branched with α(1→4) and α(1→6) linkages.
Amylopectin can contain up to ~100,000 glucose units; amylose typically ~300–500 units (source-dependent).
Glycogen (animals): storage polysaccharide in liver and muscle; highly branched, more extensively than amylopectin; up to ~1,000,000 glucose units.
Digestion and digestion rate: branched storage polysaccharides have more terminal ends and are digested more rapidly by enzymes.
Iodine test: starch solutions turn blue-black with iodine; used as a qualitative test for starch.
Cellular storage and osmotic control: glycogen and starch serve as energy reserves while minimizing osmotic stress inside cells.
18.17 Structural Polysaccharides
Structural polysaccharides provide rigidity and support.
Cellulose: unbranched glucose polymer with β(1→4) linkages; linear, forming strong hydrogen-bonded fiber networks; abundant in plant walls; major structural material in wood and cotton.
Chitin: similar to cellulose but uses N-acetylglucosamine (NAG) instead of glucose; β(1→4) linkages; provides rigidity to exoskeletons of arthropods and is found in fungal cell walls.
Differences in linkage type (β for cellulose/chitin vs α for starch/glycogen) account for differing shapes and properties (cellulose linear fibers vs spiral amylose).
Biological significance: humans cannot digest cellulose or chitin due to lack of appropriate hydrolases; cellulose serves as dietary fiber; chitin-derived glucosamine has nutritional and potential supplement uses.
Branching differences: starch and glycogen are highly branched (glycogen more so than amylopectin); cellulose and chitin are unbranched in their primary polymeric backbones.
18.18 Acidic Polysaccharides
Acidic polysaccharides contain repeating disaccharide units with acidic groups (sulfate or carboxylate) that impart negative charges; often heteropolysaccharides.
Hyaluronic acid: alternating units of N-acetylglucosamine (NAG) and D-glucuronate; role in connective tissue and lubrication (joints) and in vitreous humor of the eye; contains b(1→3) and b(1→4) linkages; long chains (~50,000 disaccharide units).
Heparin: highly sulfated polysaccharide; contains repeating disaccharide units of sulfo-glucosamine (N-sulfo) and glucuronate derivatives; extremely negative; acts as an anticoagulant by inhibiting clot formation; used medically as an anticoagulant.
Structural and functional diversity arises from sulfation patterns and the presence of sulfate and carboxylate groups.
18.19 Dietary Considerations and Carbohydrates
Dietary carbohydrates: overall balance should be about 60% of calories from carbohydrates in a typical diet; breakdown into simple vs complex.
Simple carbohydrates: monosaccharides and disaccharides; typically sweet; readily digested.
Complex carbohydrates: polysaccharides (starch, glycogen, cellulose, etc.); not sweet; often higher in fiber.
Natural vs refined sugars:
Natural sugars occur in whole foods (e.g., milk, fruit) and come with nutrients.
Refined sugars are isolated from plant sources; chemically identical to natural sugars but lack accompanying nutrients.
Be mindful of energy density and nutritional value; refined sugars can contribute calories with little nutritional benefit (empty calories).
Major dietary sources of complex carbohydrates: grains (starch and protein), vegetables (fiber), potatoes (starch), and dietary fiber from fruits/vegetables.
The glycemic response is influenced by the form and amount of carbohydrate, leading to concepts like glycemic index and glycemic load (see 18-E).
18.20 Glycolipids and Glycoproteins: Cell Recognition
Glycolipids: lipid molecules with one or more carbohydrate units attached; important in cell membranes and cell recognition.
Glycoproteins: proteins with one or more carbohydrate units; immunoglobulins are glycoproteins important in immune response.
In membranes, the carbohydrate portion often projects outward and serves as a recognition marker for cell–cell interactions, pathogen recognition, and fertilization processes.
Cerebrosides and gangliosides (glycolipids) are abundant in brain tissue; glycoproteins are central to immune recognition and receptor binding.
The prefix glyco- (from glykys, 'sweet') reflects the carbohydrate nature of these molecules.
Chemical Connections (highlights from the boxed features in the chapter)
18-A Lactose Intolerance or Lactase Persistence: genetic and physiological variability in lactase enzyme activity; lactose digestion varies by age and ethnicity; lactose intolerance is not an allergy but an enzymatic deficiency.
18-B Changing Sugar Patterns: modern sweetener trends show a shift from sucrose to high-fructose corn syrup (HFCS) for economic and processing reasons; HFCS composition and processing provide sweetness with different ratios of fructose to glucose.
18-C Sugar Substitutes: artificial sweeteners (saccharin, cyclamate, aspartame, sucralose, neotame) offer low to zero calories; safety concerns and regulatory stances vary by country; heat stability differs among substitutes.
18-D Blood Types and Oligosaccharides: blood type is determined by membrane oligosaccharide markers (A, B, AB, O); the markers involve four-mugar carbohydrates, with a fifth unit determining A or B type; the markers are biosynthesized via specific enzymes; Bombay phenotype and other rare variations exist.
18-E Glycemic Response, Glycemic Index, and Glycemic Load: GI measures blood glucose response to a carbohydrate-containing food relative to a standard (glucose); GL accounts for the actual carbohydrate content in a serving; higher GI/GL foods cause faster glucose spikes; factors affecting GI/GL include food combination, fat/protein content, processing, and individual variation.
Concepts to Remember
Biochemistry basics: molecules found in living systems interact to sustain life; carbohydrates are polyhydroxy aldehydes/ketones or their derivatives.
Carbohydrates are classified by size (mono-, di-, oligo-, poly-), and by structure (aldoses vs ketoses).
Chirality and stereoisomerism are fundamental in carbohydrates, impacting enzyme recognition and physiological activity.
Monosaccharides form cyclic hemiacetals; anomeric carbon becomes chiral, producing α/β anomers.
Glycosidic linkages connect monosaccharides in disaccharides and polysaccharides; linkage type and stereochemistry (α vs β) determine properties and digestibility.
Digestion and metabolism involve oxidation/reduction, glycoside formation, phosphorylation, and amino sugar formation; these reactions underpin energy production and structural roles.
Dietary carbohydrates range from simple sugars to complex polysaccharides; GI and GL provide tools to understand postprandial glucose responses.
Glycolipids and glycoproteins enable cell recognition, signaling, and immune functions.
Important LaTeX notes for study references:
Carbohydrate general formula: (historical hydrate viewpoint) or ; term carbohydrate persists.
Monosaccharide classification: aldose vs ketose; triose, tetrose, pentose, hexose; D/L designations depending on highest-numbered chiral center.
Open-chain to cyclic conversion and anomeric carbon formation lead to anomers: of cyclic monosaccharides; for glucose, a predominance of β-D-glucose in solution is typical (e.g., 63% β, 37% α at equilibrium).
Glycosidic linkages in common disaccharides: maltose (α(1→4)); cellobiose (β(1→4)); lactose (β(1→4)); sucrose (α,β(1→2)); nonreducing nature of sucrose due to both anomeric carbons involved in glycosidic bonding.
Polysaccharide branching: amylose (unbranched, α(1→4)); amylopectin (branched, α(1→4) and α(1→6)); glycogen (highly branched; α(1→4) and α(1→6) linkages); cellulose (β(1→4)); chitin (β(1→4) with N-acetylglucosamine).
Acidic polysaccharides: hyaluronic acid (N-acetylglucosamine and glucuronate); heparin (sulfated derivative polymers; anticoagulant).
If you’d like, I can tailor these notes further to a particular exam format (e.g., more practice problems, or a condensed “cheat sheet” version for quick review).