Carbohydrates and Glycoproteins - Study Notes

CHAPTER 10 Overview: Carbohydrates and Glycoproteins

  • Objectives (highlights):

    • Recognize features of monosaccharides for naming
    • Write Fischer projections for monosaccharides and, given the linear structure, draw Haworth projections of alpha and beta cyclic forms (and vice-versa)
    • Determine stereochemical features: label chirality centers, draw enantiomers, identify monosaccharides as D or L
    • Compare disaccharides and polysaccharides and their physiological roles
    • Describe 3 classes of glycoproteins and their biological roles

  • Slides with blanks noted in the transcript: 2-3, 5, 8, 10, 14, 19, 23, 25, 28, 30-33, 37, 39, 41

Carbohydrates and Intro to Monosaccharides

  • General formula for carbohydrates: (extCH<em>2extO)</em>n (n ≥ 3)( ext{CH}<em>2 ext{O})</em>n \, (n \, \ge\, 3)

    • Recognized by a large number of hydroxyl groups (-OH)

  • Monosaccharides = simple sugars

    • Described by and ____ ___ (as per transcript blanks)
    • May be aldoses or ketoses

  • Carbohydrate types by size:

    • Monosaccharides
    • Disaccharides
    • Trisaccharides
    • Polysaccharides: complex carbs

  • Triose, Tetroses, Pentoses, Hexoses labeling by carbon count

    • Triose: 3 C
    • Tetroses: 4 C
    • Pentoses: 5 C
    • Hexoses: 6 C

  • Aldoses vs. Ketoses (examples):

    • Aldopentose (e.g., ribose; aldehyde at C1)
    • Aldohexose (e.g., glucose; aldehyde at C1)
    • Ketohexose (e.g., fructose; ketone at C2)

  • Examples shown in the slides for common aldoses/ketoses:

    • D-Ribose, D-Arabinose, D-Xylose, D-Lyxose, D-Ribose (and others) in aldose family
    • D-Glucose (an aldose, hexose)
    • D-Fructose (a ketohexose)
    • D-Altrose, D-Allose, D-Galactose, D-Idose, D-Mannose, D-Gulose, D-Talose (various aldoses; stereoisomers)

  • Fischer vs. Haworth projections (concepts):

    • Fischer projection: linear arrangement with horizontal bonds project out of the plane; vertical bonds go back
    • Haworth projection: cyclic form; orientation of groups depends on ring form (pyranose or furanose)
    • Rule: The enantiomeric –OH groups on the right in Fischer projections point down in Haworth projections

Chirality and Stereochemistry in Monosaccharides

  • Chirality and D/L classification:

    • Mirror images, non-superimposable
    • D vs L defined by the configuration at the chiral center farthest from the carbonyl group in the Fischer projection (for hexoses, C5)
    • Most vertebrates have the D configuration for monosaccharides
    • For amino acids, only the L isomer is found in proteins

  • Stereoisomers terminology:

    • Enantiomers: nonsuperimposable mirror images; optical isomers
    • Diastereomers: not mirror images; different at one or more chiral centers
    • Epimers: differ at exactly one chiral center
    • Anomers: differ at the new asymmetric carbon formed on ring closure (anomeric carbon)
    • Meso compounds (excluded here) are achiral despite having stereocenters

  • Isomerization concepts:

    • D-glucose ⇌ D-fructose interconversion (aldose–ketose isomerization)
    • Glucose ⇌ Mannose is an epimerization at C-2

Ring Formation and Anomerism

  • Functional groups involved in ring formation:

    • Hemiacetal: an –OH and OR group bonded to the same carbon
    • Acetal: two OR groups bonded to the same carbon

  • Cyclization: sugars form ring structures via intramolecular reaction

    • The hydroxyl group on C5 (or appropriate ring-forming OH) attacks the carbonyl carbon
    • In Haworth projections, substituents that are on the right side of the Fischer projection point down in the Haworth (for sugars drawn in their standard orientation)

  • Cyclization to Haworth (examples):

    • D-Glucose (open-chain) ⇌ α-D-Glucopyranose (pyranose) and β-D-Glucopyranose
    • Defined anomers: α (OH on anomeric carbon is trans to CH2OH group) and β (cis to CH2OH)
    • D-Fructose cyclization to form furanose/pyranose forms (α- and β- examples shown)

  • Pentose cyclization and anomers:

    • D-Ribose forms α-D-ribose and β-D-ribose in furanose form
    • α/β designation around the anomeric carbon (C1 in aldoses, C2 in fructose examples)

  • Nomenclature and ring types:

    • Furanose: five-membered ring
    • Pyranose: six-membered ring
    • D-Fructose can form both furanose (5-member) and pyranose (6-member) forms

  • Equilibrium among Fischer and Haworth forms:

    • Interconversion occurs between open-chain (Fischer) and cyclic (Haworth) forms

Examples of Specific Monosaccharides in Ring Form

  • Common monosaccharides in ring form (notation examples):

    • a-D-Glucopyranose (pyranose form of glucose, alpha)
    • β-D-Glucopyranose (pyranose form of glucose, beta)
    • a-D-Galactopyranose, β-D-Galactopyranose
    • a-D-Mannopyranose, β-D-Mannopyranose
    • a-D-Fructofuranose, β-D-Fructofuranose (fructose furanose)
    • a-D-Ribofuranose, β-D-Ribofuranose (ribose furanose forms)
    • a-D-Ribopyranose, β-D-Ribopyranose (ribose pyranose forms)

  • Abbreviations and shorthand for ring forms are commonly used in teaching and literature

Reactions of Monosaccharides

  • Functional groups allow several types of chemical reactions:
    • Oxidation, reduction
    • Isomerization (aldose↔ketose interconversion; epimerization)
    • Esterification
    • Glycoside formation (glycosylation) – enzymatic bonding to another molecule via the anomeric carbon
    • Glycation – non-enzymatic addition of a carbohydrate to another molecule
      • Important in aging and diabetes contexts (non-enzymatic glycation)

Reducing Sugars and Glycosidic Bonding

  • Anomeric carbon rule:

    • The anomeric carbon is the carbonyl carbon in the Fischer projection and is the carbon that becomes the acetal/hemiactal linkage in the cyclic form
    • Anomeric carbon can be oxidized; sugars that can be oxidized are reducing sugars

  • Reducing vs non-reducing sugars:

    • Reducing sugar: has a free anomeric carbon (not involved in a glycosidic bond) that can reduce other reagents (e.g., Cu2+ to Cu+), forming Cu2O in Benedict’s test
    • Non-reducing sugar: the anomeric carbon is involved in a glycosidic bond, hence it cannot be oxidized by mild oxidizing agents

  • Glycosidic bonds (definition):

    • Glycosidic bond = linkage between the anomeric carbon of one sugar and a second group (which may be a hydroxyl on another sugar or another molecule)
    • Notation examples:
    • α(1→4): glycosidic bond from anomeric carbon of one sugar (α) to C-4 of the next sugar
    • β(1→4): similar link but with β configuration at the anomeric center
    • A given disaccharide may have α or β at the anomeric carbon of one or both sugars, leading to multiple possible disaccharides (as seen with lactose)

Disaccharides: Examples and Nomenclature

  • Lactose: disaccharide built from galactose and glucose

    • Structure: ẞ-D-galactopyranosyl-(1-4)-D-glucose
    • Anomeric configuration: galactose in the β form linked to glucose

  • Sucrose:

    • Structure: α-D-glucopyranosyl-(1→2)-β-D-fructofuranose
    • Both anomeric carbons are involved in the linkage: glucose C1 (anomeric) to fructose C2 (anomeric)

  • Maltose:

    • Structure: α-D-glucopyranosyl-(1-4)-α-D-glucopyranose
    • Reducing end is the anomeric carbon of the non-reducing glucose unit; maltose is typically a reducing sugar because one end retains a free anomeric carbon (depending on linkage orientation; the slide shows α-1,4 linkage)

  • Glycosidic bond types to recognize:

    • Lactose: β(1→4) linkage (Gal–Glc)
    • Sucrose: α(1→2) linkage between glucose and fructose (both anomeric carbons involved)
    • Maltose: α(1→4) linkage between glucose units

Polysaccharides: Plant and Animal Storage and Structural Polysaccharides

  • Starch (plants): polymers of glucose for energy storage

    • Two types:
    • Amylose: unbranched; forms a left-handed helix
    • Amylopectin: branched; mainly α(1→4) linkages with α(1→6) branches

  • Glycogen (animals): energy storage polymer

    • Highly branched; more extensive α(1→6) branches than starch (branch points roughly every ~12 residues)
    • Protein component: glycogenin (acts as a starter for glycogen synthesis)

  • Cellulose (plants and some bacteria for structural support):

    • Residues linked by β(1→4) glycosidic bonds
    • Forms a hydrogen-bonding network; provides strong structural material
    • Animals cannot digest cellulose due to the β-linkages

  • Chitin (arthropods, crustaceans):

    • β(1→4) glycosidic bonds
    • Repeating N-acetylglucosamine units (GlcNAc)
    • Provides structural support (exoskeletons)

  • Mapping of glycosidic bonds in common polysaccharides:

    • Starch: mainly α(1→4) with α(1→6) branches (amylopectin)
    • Glycogen: α(1→4) backbone with frequent α(1→6) branches
    • Cellulose: β(1→4)
    • Chitin: β(1→4) with N-acetylglucosamine units

Glycoproteins and Glycoconjugates

  • Glycoproteins: oligosaccharides covalently attached to polypeptides

    • N-linked to asparagine (Asn) side chains
    • O-linked to serine (Ser) or threonine (Thr) side chains
    • Functions include cell signaling, protein stability, cell-cell recognition, and membrane components

  • Oligosaccharide examples on glycoproteins (N-linked):

    • Common sugars abbreviated: Fuc (fucose), Gal (galactose), GlcNAc (N-acetylglucosamine), Glc (glucose), Man (mannose), Sia (sialic acid)
    • Shown in representative structures for two N-linked oligosaccharides

  • N-acetylglucosamine (GlcNAc) on Ser or Thr:

    • Very common post-translational modification (O-GlcNAcylation)
    • Also called GlcNAc or NAG
    • Glycoconjugates arise when carbohydrates attach to proteins and lipids
    • Three main types of glycoconjugates:
    • Glycoproteins
    • Proteoglycans
    • Mucins

  • Proteoglycans:

    • Distinguished by high carbohydrate content (≈95% by weight)
    • Core protein with glycosaminoglycan (GAG) chains attached
    • Located in extracellular matrix of connective tissue (e.g., cartilage)
    • Built from repeating disaccharides

  • Glycosaminoglycans (GAGs) in proteoglycans:

    • Examples shown: Heparin, Dermatan sulfate, Chondroitin sulfate, Keratan sulfate, Hyaluronate
    • Heparin: potent anticoagulant; stops blood clotting
    • Structure: heteropolysaccharides composed of repeating disaccharides with various sulfation patterns
    • The disaccharide units typically include an uronic acid and a hexosamine (e.g., GlcNAc, GalNAc)
    • General pattern (illustrative):
    • Heparin: repeating units containing uronic acid (IdoA or GlcA) and GlcNS or GlcNSO3; sulfation contributes to function

  • Mucins (mucoproteins):

    • Regions rich in O-glycosylation on serine and threonine residues, especially in VNTR (Variable Number of Tandem Repeats) regions
    • Mucins are often overexpressed in bronchitis and cystic fibrosis

  • Summary relationships:

    • Glycoproteins = protein components with covalently attached carbohydrates (N- or O-linked)
    • Proteoglycans = a subset with extensive GAG chains; primarily carbohydrate by weight; structural roles in extracellular matrix
    • Mucins = highly glycosylated glycoproteins with VNTRs; protect and lubricate (e.g., mucus)

Quick Reference: Key Terminology and Notation

  • General carbohydrate formula: (extCH<em>2extO)</em>n (n≥3)( ext{CH}<em>2 ext{O})</em>n \, (n \ge 3)
  • Monosaccharide forms:
    • Aldose vs. ketose
    • Aldohexose: e.g., glucose; aldopentose: e.g., ribose; ketohexose: e.g., fructose
  • Ring forms:
    • Pyranose (6-membered ring, e.g., glucopyranose)
    • Furanose (5-membered ring, e.g., ribofuranose, fructofuranose)
  • Anomers:
    • α vs. β at the anomeric carbon (introduced on ring formation)
  • Glycosidic bonds:
    • Notation examples: α(1→4)\alpha(1\to 4), β(1→4)\beta(1\to 4), α(1→2)\alpha(1\to 2), etc.
  • Reducing vs non-reducing sugars:
    • Reducing: free anomeric carbon; can reduce Cu2+ to Cu+ (Cu2O formation)
    • Non-reducing: anomeric carbon involved in a glycosidic bond; cannot reduce
  • Disaccharide examples:
    • Lactose: ẞ-D-galactopyranosyl-(1-4)-D-glucose
    • Sucrose: α-D-glucopyranosyl-(1→2)-β-D-fructofuranose
    • Maltose: α-D-glucopyranosyl-(1-4)-α-D-glucopyranose
  • Polysaccharides and roles:
    • Starch (amylose and amylopectin) = plant energy storage
    • Glycogen = animal energy storage; highly branched
    • Cellulose = structural β(1→4) links; indigestible by humans
    • Chitin = structural β(1→4) linkages with N-acetylglucosamine
  • Glycoproteins vs proteoglycans vs mucins:
    • Glycoproteins: N-linked to Asn; O-linked to Ser/Thr
    • Proteoglycans: protein core with GAG chains; extracellular matrix
    • Mucins: VNTR regions; heavy O-glycosylation; mucus-forming glycoproteins

Connections to broader concepts

  • Metabolic context: monosaccharide isomers interconvertible (aldose↔ketose; epimers) feed into glycolysis and energy metabolism
  • Structure–function relationships: ring form, anomeric configuration, and glycosidic linkages determine digestibility, recognition by enzymes, and cross-species compatibility
  • Biological relevance: glycosylation patterns on proteins influence cell signaling, adhesion, immune recognition, and development; proteoglycans and GAGs contribute to extracellular matrix integrity and hydration; mucins protect mucosal surfaces
  • Pathophysiology: aberrant glycosylation patterns are associated with diseases (e.g., cystic fibrosis and bronchitis via mucins; abnormal proteoglycan sulfation in connective tissue disorders)

Notes on content provenance and completeness

  • The transcript includes several slide blanks (e.g., blanks in 2-3, 5, 8, etc.). These have been preserved in the notes to reflect the source material and to guide you to review or fill in during study.
  • Numerous figures and projections (Fischer → Haworth, boat vs. chair, etc.) are described conceptually; the notes summarize the concepts and naming conventions that students typically need to master for the exam.