Rucete ✏ Lehninger Principles of Biochemistry In a Nutshell
7.1 Monosaccharides and Disaccharides
This chapter introduces the basic structures, stereochemistry, and chemical properties of simple carbohydrates, focusing on monosaccharides and disaccharides. It explains how sugars form cyclic structures, exhibit chirality, and combine through glycosidic bonds to form larger saccharides essential for energy storage and biological recognition.
Structure and Types of Monosaccharides
• Monosaccharides are the simplest carbohydrates, containing aldehyde or ketone groups and multiple hydroxyl groups.
• They are colorless, crystalline solids, soluble in water but insoluble in nonpolar solvents, and most taste sweet.
• Aldoses contain an aldehyde group at the end of the carbon chain, while ketoses have a ketone group in an internal position.
• Common examples include glyceraldehyde (an aldotriose) and dihydroxyacetone (a ketotriose).
Sweetness and Taste Receptors
• Sweetness perception is mediated by TAS1R2 and TAS1R3 receptor proteins on tongue taste buds.
• Natural sugars (glucose, fructose, sucrose, lactose) bind both subunits, whereas artificial sweeteners like aspartame bind only one.
• Stereochemistry determines sweetness — only the (S,S)-aspartame configuration stimulates the sweet receptor, while (R,S)-aspartame activates a bitter receptor.
Classification of Monosaccharides
• Monosaccharides are categorized by carbon number: trioses (3C), tetroses (4C), pentoses (5C), hexoses (6C), and heptoses (7C).
• Hexoses like glucose (an aldohexose) and fructose (a ketohexose) are the most abundant in nature.
• D-ribose and 2-deoxy-D-ribose are critical components of RNA and DNA.
Stereochemistry and Chirality
• Except for dihydroxyacetone, all monosaccharides have one or more chiral carbons and therefore optical isomers.
• Glyceraldehyde defines the D- and L- configurations: if the hydroxyl group on the reference carbon is on the right, it is a D-sugar; on the left, an L-sugar.
• Of the 16 aldohexoses, half are D forms and half L forms; most biological sugars are D isomers.
• Epimers are sugars differing only at one chiral center (e.g., D-glucose vs. D-mannose or D-galactose).
Cyclic Structures of Monosaccharides
• In aqueous solution, sugars with five or more carbons predominantly form ring (cyclic) structures.
• The carbonyl group reacts intramolecularly with a hydroxyl group to form a hemiacetal (from aldehydes) or hemiketal (from ketones).
• This reaction generates a new chiral center at the carbonyl carbon, forming two anomers (α and β).
• For glucose, the cyclic forms are α-D-glucopyranose and β-D-glucopyranose; for fructose, α- and β-D-fructofuranose.
• Anomers interconvert in solution via mutarotation, establishing an equilibrium mixture of α, β, and linear forms.
Fischer and Haworth Representations
• Fischer projections show linear forms, while Haworth perspectives depict cyclic forms more accurately.
• In Haworth formulas, hydroxyl groups on the right in Fischer projection point down, and those on the left point up.
• When the anomeric hydroxyl is on the same side as C-6, it is the β form; on the opposite side, it is the α form.
• Pyranoses have six-membered rings; furanoses have five-membered rings.
Conformations of Sugar Rings
• Six-membered pyranose rings are not planar; they adopt chair conformations that minimize steric strain.
• The α and β configurations require bond breaking to interconvert, but chair conformers can interconvert freely.
Hexose Derivatives
• Sugar derivatives arise when hydroxyl groups are replaced or oxidized:
• Amino sugars (glucosamine, galactosamine, mannosamine) have an amino group at C-2, often acetylated as N-acetylglucosamine.
• Deoxy sugars (e.g., L-fucose, L-rhamnose) replace a hydroxyl group with hydrogen.
• Oxidation of C-1 forms aldonic acids (gluconic acid), while oxidation of C-6 forms uronic acids (glucuronic acid).
• Sialic acids (e.g., N-acetylneuraminic acid) have nine-carbon backbones and serve as recognition molecules on cell surfaces.
• Phosphorylated sugars (e.g., glucose 6-phosphate) play key roles in metabolism and are trapped inside cells due to their charge.
Reducing Sugars
• Monosaccharides with free aldehyde groups can reduce Cu²⁺ to Cu₂O under alkaline conditions, forming a red precipitate.
• All aldoses are reducing sugars since cyclic forms equilibrate with open-chain aldehyde forms.
• Ketoses like fructose can tautomerize into aldoses and are also reducing sugars.
• The reducing property forms the basis for clinical glucose testing.
Blood Glucose and Diabetes (Medical Insight)
• Glucose oxidase tests detect blood glucose using enzyme-mediated oxidation reactions producing a measurable color change.
• Chronic glucose exposure leads to nonenzymatic glycation of hemoglobin, forming HbA1c, which reflects average blood glucose over ~120 days.
• Normal HbA1c is about 5%; diabetic patients may reach 13% or higher.
• Advanced glycation end products (AGEs) can cross-link proteins, damaging tissues such as kidneys, eyes, and blood vessels.
Disaccharides and Glycosidic Bonds
• Two monosaccharides join by an O-glycosidic bond between the anomeric carbon of one sugar and a hydroxyl of another.
• Formation of this bond produces an acetal, rendering the sugar nonreducing if no free anomeric carbon remains.
• The reducing end of a disaccharide retains a free anomeric carbon capable of oxidation.
Naming Disaccharides
• Names are written from nonreducing to reducing end and specify:
1. The α or β configuration at the anomeric carbon forming the bond.
2. The ring type (pyrano- or furano-).
3. The linked carbon atoms (e.g., 1→4).
4. The full name of the second monosaccharide.
• Example: maltose is α-D-glucopyranosyl-(1→4)-α-D-glucopyranose, abbreviated as Glc(α1→4)Glc.
Common Disaccharides
• Maltose — two glucose units joined by α(1→4); a reducing sugar found in starch hydrolysis.
• Lactose — galactose and glucose joined by β(1→4); a reducing sugar found in milk.
• Sucrose — glucose and fructose joined by α(1→2)β; a nonreducing sugar, stable for energy storage in plants.
• Trehalose — two glucose units joined by α(1→1)α; a nonreducing sugar serving as energy storage and antifreeze in insects.
Lactose Intolerance
• Lactase hydrolyzes lactose into glucose and galactose for absorption in the small intestine.
• Deficiency in lactase causes lactose intolerance, leading to bloating, cramps, and diarrhea due to bacterial fermentation and osmotic imbalance.
In a Nutshell
Monosaccharides are the fundamental building blocks of carbohydrates, existing as chiral molecules that often form cyclic structures. Through oxidation, substitution, and phosphorylation, they yield diverse biological derivatives. When two monosaccharides join via glycosidic bonds, they form disaccharides with distinct properties and roles. These structural and chemical variations underpin carbohydrate metabolism, energy storage, and biological signaling.