Timberlake Chemistry: Carbohydrates Study Guide

Introduction to Carbohydrates

• Carbohydrates serve as a major source of energy in the human diet and are composed of the elements carbon, hydrogen, and oxygen.
• They are also known as saccharides, a term derived from the word for "sugars."
• Production in Plants:     * Carbohydrates such as glucose are produced via photosynthesis.     * Plants synthesize these molecules from $CO_2$, $H_2O$, and solar energy.
• Oxidation in Living Cells:     * Carbohydrates are oxidized within cells to produce energy, $CO_2$, and $H_2O$.     * Respiration (breathing) is defined as the gaseous exchange of carbon dioxide and oxygen for use by the body.
• General Formulas:     * The general formula for carbohydrates is $C_n(H_2O)_n$ or $C_nH_{2n}O_n$.

Classification and Types of Carbohydrates

• Carbohydrates are categorized based on their complexity:     * Monosaccharides: The simplest form of carbohydrates.     * Disaccharides: Consist of two monosaccharide units.     * Polysaccharides: Contain many monosaccharide units.

Monosaccharide Structure and Nomenclature

• Basic Structure:     * Monosaccharides consist of a chain of three to eight carbon atoms with several hydroxyl ($-OH$) groups attached.     * Every carbon has a hydroxyl group except for the carbonyl carbon.
• Functional Group Classification:     * Aldoses: Monosaccharides containing an aldehyde group at the end of the chain.     * Ketoses: Monosaccharides containing a ketone group.
• Carbon Count Classification:     * Triose: Three carbon atoms.     * Tetrose: Four carbon atoms.     * Pentose: Five carbon atoms.     * Hexose: Six carbon atoms.
• Phylogeny of D-Aldoses (Key Examples):     * Triose: D-(+)-glyceraldehyde.     * Tetroses: D-(-)-erythrose, D-(-)-threose.     * Pentoses: D-(-)-ribose, D-(-)-arabinose, D-(+)-xylose, D-(-)-lyxose.     * Hexoses: D-(+)-allose, D-(+)-altrose, D-(+)-glucose, D-(+)-mannose, D-(-)-gulose, D-(-)-idose, D-(+)-galactose, D-(+)-talose.

Chirality and Stereoisomers

• Structural Isomers: Molecules with the same molecular formula but different bonding arrangements.
• Stereoisomers: Molecules where atoms are bonded in the same sequence but differ in their spatial arrangement.
• Chirality:     * Chiral: Objects or molecules that have non-superimposable mirror images (e.g., left and right hands).     * Achiral: Objects or molecules whose mirror images are identical and can be superimposed.
• Enantiomers: A specific type of stereoisomer consisting of non-superimposable mirror images.
• Chiral Carbon Atoms: A carbon atom is chiral if it is bonded to four different atoms or groups.

Fischer Projections

• A Fischer Projection is a 2D representation of a 3D molecule.
• Structural Rules:     * The most oxidized group is placed at the top.     * Vertical lines represent bonds projecting away from the viewer (back).     * Horizontal lines represent bonds projecting toward the viewer (forward).     * Intersections represent carbon atoms, which are typically chiral centers.
• D and L Designations:     * Determined by the position of the $-OH$ group on the chiral carbon farthest from the carbonyl group.     * L-isomer: The $-OH$ group is on the left.     * D-isomer: The $-OH$ group is on the right.     * To draw the mirror image (L-isomer) of a D-sugar, reverse the positions of all $-H$ and $-OH$ groups on the horizontal lines.

Biological and Clinical Significance of Enantiomers

• Biological Effects: Often, only one enantiomer is biologically active or produces a specific effect.
• Carvone:     * One enantiomer (from spearmint) smells/tastes like spearmint.     * The other enantiomer (from caraway) smells/tastes like caraway seeds in rye bread.
• Parkinson’s Disease:     * L-dopa is an effective treatment because it converts to dopamine in the brain and raises serotonin levels.     * D-dopa is medically ineffective for this treatment.
• Drugs and Safety:     * Thalidomide: Historically significant tragedy emphasizing the need for drug safety and regulation regarding enantiomers.     * Antihistamines: Examples include Zyrtec (Cetirizine HCl) and its enantiopure counterpart Xyzal (Levocetirizine).

Key Monosaccharides and Their Roles

• D-Glucose ($C_6H_{12}O_6$):     * The most common hexose; known as dextrose or blood sugar.     * Found in fruits, vegetables, corn syrup, and honey.     * A building block for sucrose, lactose, cellulose, and glycogen.
• D-Galactose ($C_6H_{12}O_6$):     * An aldohexose obtained from the hydrolysis of lactose (milk sugar).     * Essential for cellular membranes in the brain and nervous system.     * Galactosemia: A condition where the enzyme to convert galactose to glucose is missing, leading to accumulation in blood and tissue. If untreated, it causes cataracts, liver disease, failure to thrive, and mental retardation.
• D-Fructose ($C_6H_{12}O_6$):     * A ketohexose and the sweetest of all carbohydrates (twice as sweet as sucrose).     * Found as a hydrolysis product of sucrose.     * High-fructose corn syrup (HFCS) is made by enzymatically breaking down sucrose into glucose and fructose.

Clinical Links to Health: Blood Glucose Regulation

• Normal Levels: Blood glucose typically ranges from $70$ to $90\,mg/dL$.
• Hyperglycemia and Diabetes Mellitus:     * Occurs when the pancreas cannot produce enough insulin.     * Glucose levels can rise to $350\,mg/dL$ of plasma.     * Symptoms: Excessive thirst, excessive urination, weight loss, and increased appetite.     * In older adults, it is often linked to excessive weight gain.
• Hypoglycemia:     * Blood glucose drops to levels as low as $40\,mg/dL$.     * Caused by overproduction of insulin.     * Symptoms: Dizziness, general weakness, and muscle tremors.     * Treatment: A diet of several small meals high in protein and low in carbohydrates.

Haworth Structures and Cyclic Forms

• Pentose and hexose sugars are most stable as five- or six-atom rings.
• Formation: Produced by the reaction of a carbonyl group and a hydroxyl group within the same molecule to form a cyclic hemiacetal.
• Drawing Haworth Structures:     1. Turn the Fischer projection clockwise by $90^{\circ}$.     2. Fold the chain to bond the oxygen on carbon 5 to carbon 1.
• Anomers:     * New isomers formed at the anomeric carbon (Carbon 1 for aldoses).     * $\alpha$-anomer: The $-OH$ group on C1 is drawn down.     * $\beta$-anomer: The $-OH$ group on C1 is drawn up.
• Mutarotation: In solution, cyclic structures open and close, allowing $\alpha$-D-glucose and $\beta$-D-glucose to interconvert. Only a trace amount of open-chain form exists at any time.
• Galactose vs. Glucose: Galactose differs only at Carbon 4, where the $-OH$ is drawn above the ring in the Haworth structure.
• Fructose: Forms a five-atom ring (furanose) where Carbon 2 is the anomeric carbon.

Chemical Properties of Monosaccharides

• Sugar Alcohols:     * Produced by reducing the carbonyl group; named by replacing "-ose" with "-itol".     * Examples: D-Sorbitol, D-Xylitol (from xylose), and D-Mannitol (from mannose).     * Used as sweeteners in diet drinks, sugarless gum, and diabetic products.
• Oxidation and Reducing Sugars:     * Monosaccharides with an aldehyde group (or those that can isomerize to one) can be oxidized to carboxylic acids (sugar acids).     * Sugar acids are named by replacing "-ose" with "-onic acid".     * Benedict’s Test: Uses $Cu^{2+}$ (blue solution). If a reducing sugar is present, $Cu^{2+}$ is reduced to $Cu^+$ (brick-red precipitate).     * Reducing Sugars: Monosaccharides like glucose, galactose, and fructose are all reducing sugars.
• Fructose Isomerization: Although fructose is a ketone, it can be oxidized in basic Benedict’s solution because it rearranges into glucose.

Disaccharides

• Formed via a dehydration reaction between two monosaccharides, creating a glycosidic bond.
• Maltose (Malt Sugar):     * Composition: Glucose + Glucose.     * Bond: $\alpha$-(1,4)-glycosidic bond.     * Found in cereals, candies, and brewing; obtained from starch hydrolysis.
• Lactose (Milk Sugar):     * Composition: Glucose + Galactose.     * Bond: $\beta$-(1,4)-glycosidic bond.     * Comprises $6-8\%$ of human milk and $4-5\%$ of cow's milk.
• Sucrose (Table Sugar):     * Composition: $\alpha$-D-Glucose + $\beta$-D-Fructose.     * Bond: $\alpha,\beta$-(1,2)-glycosidic bond.     * Source: Sugar cane ($20\%$ by mass) or sugar beet ($15\%$ by mass).     * Non-reducing sugar: Sucrose cannot form an open chain or be oxidized; it does not react with Benedict’s reagent.

Sweetness and Artificial Sweeteners

• Relative Sweetness (Sucrose = 100):     * Lactose: $16$     * Galactose: $30$     * Maltose: $33$     * Sorbitol: $60$     * Glucose: $75$     * Maltitol: $80$     * Xylitol: $100$     * Fructose: $175$
• Artificial (Noncarbohydrate) Sweeteners:     * Aspartame (NutraSweet, Equal): Made from aspartic acid and phenylalanine methyl ester. Sweetness: $18,000$.     * Saccharin (Sweet’N Low): Used for over 60 years. Banned in Canada due to bladder tumor concerns in studies, but FDA-approved in the US. Sweetness: $45,000$.     * Sucralose (Splenda): Made by replacing sucrose hydroxyl groups with chlorine. Sweetness: $60,000$.     * Neotame: A modification of aspartame. It has a large alkyl group that prevents enzymes from breaking the amide bond, so phenylalanine is not released. Sweetness: $1,000,000$ (Table 15.2) or $10,000$ (Page 47 text).

Polysaccharides

• Long polymers of D-glucose units.
• Starch:     * Storage form of glucose in plants (rice, wheat, potatoes).     * Amylose ($\sim 20\%$): Unbranched continuous chain of $250$ to $4000$ $\alpha$-D-glucose units with $\alpha$-(1,4) bonds. Coiled in a helix.     * Amylopectin ($\sim 80\%$): Branched chain containing $\alpha$-(1,4) bonds and $\alpha$-(1,6) glycosidic bonds at branch points.     * Digestion: Hydrolyzed by amylase (saliva) and maltase (intestine) into dextrins, then maltose, then glucose.
• Glycogen (Animal Starch):     * Storage form of glucose in animal livers and muscles.     * Similar to amylopectin but more highly branched ($\alpha-1,6$ branches occur every $10-15$ units).
• Cellulose:     * Major structural unit of wood and plants.     * Unbranched chains with $\beta$-(1,4)-glycosidic bonds.     * Insoluble in water and more resistant to hydrolysis.     * Indigestible by humans because humans lack the enzyme to break $\beta$-(1,4) bonds.

Specialized Compounds: Aminoglycosides and Glycosaminoglycans

• Aminoglycoside Antibiotics:     * Contain two or more amino sugars connected by glycosidic bonds.     * Neomycin: Found in topical creams like Neosporin, ointments, and eyedrops.
• Glycosaminoglycans:     * Unbranched polysaccharides of repeating disaccharide units (amino sugar + uronic acid or galactose).     * Highly polar and negatively charged; function as lubricants and cushions.     * Keratan Sulfate: Found in the cornea, cartilage, bone, and animal horns. Unsulfonated keratan deposits can cause corneal cloudiness.