Chapter 20. Carbohydrates
Recommended Article : 【Organic Chemistry】 Organic Chemistry Table of Contents
4. Glycolipids
6. Carbohydrate Recognition Proteins
a. Composition of Living Organisms
1. Monosaccharides
⑴ Overview
① Monosaccharides exhibit linear structures in the solid state and cyclic structures in aqueous solution.
○ Mechanism : Nucleophilic addition reaction of aldehydes
○ Linear structure in glucose: Oxygen at position e attacks carbon at position 1, forming a cyclic structure.
Figure 1. Linear and Cyclic Glucose
○ Convex face approach (outside attack), concave face approach (inside attack)
② All monosaccharides are reducing sugars: They have strong reducing abilities and are easily oxidized themselves.
⑵ Glucose, Fructose, Galactose, Mannose
① Isomeric relationship : Glucose, fructose, galactose, and mannose have the same composition but different structures.
② Galactose : Differs only in the arrangement of the 4th carbon from glucose.
③ Aldoses : Monosaccharides with an aldehyde group, strong tendency to undergo oxidation through carbonyl group
○ Examples : Glucose, galactose, mannose
④ Ketoses : Monosaccharides with a ketone group, strong stability
○ Example : Fructose (contributes to non-reducing sugar property of sucrose)
⑤ HFCS (High-Fructose Corn Syrup)
○ Approximately half of glucose converted to fructose using isomerase enzyme
○ Fructose much sweeter than glucose
⑶ 6-carbon sugar derivatives
① N-acetylglucosamine (NAG)
○ Unit of chitin and peptidoglycan
○ Most abundant organic molecule in animals
② N-acetylgalactosamine (NAGal)
○ Most abundant organic molecule in vertebrates
○ Major constituent of cartilage
○ Determines blood type on red blood cell membrane
○ Blood type : Determined by attaching fucose to the surface of red blood cells (indicated by ■)
○ O antigen : Absent - Galactose - N-acetylgalactosamine - Galactose - Glucose - Sphingosine and fatty acids
○ A antigen : N-acetylgalactosamine - Galactose - N-acetylgalactosamine - Galactose - Glucose - Sphingosine and fatty acids
○ B antigen : Galactose - Galactose - N-acetylgalactosamine - Galactose - Glucose - Sphingosine and fatty acids
③ N-acetylmuramic acid
④ N-acetylneuraminic acid or sialic acid
○ Ganglioside : Glycosphingolipid with attached sialic acid on cell membrane exterior of mammalian cells
○ Sialic acid added to glycoproteins during glycosylation
○ Important for brain development
○ Tay-Sachs disease : Accumulation of sialic acid in nervous system due to lack of degradation
2. Disaccharides
⑴ Overview
① Disaccharides formed by glycosidic linkage between two monosaccharides
⑵ Maltose
① Two α glucose molecules linked by α 1 → 4 linkage
② Also known as malt sugar or maltose
③ Found in germinating seeds
⑶ Cellobiose
① Two β glucose molecules linked by β 1 → 4 linkage
⑷ Lactose
① Galactose linked to glucose by β 1 → 4 linkage
② Optically active
③ Capable of mutarotation: Change in optical properties due to change in arrangement in equilibrium state
Figure 2. Mutarotation of Lactose
⑸ Sucrose
① Glucose linked to fructose by α 1 → 2 linkage
② Also known as table sugar
③ Only non-reducing disaccharide among disaccharides
④ Transports carbohydrates in plant phloem
3. Oligosaccharides
⑴ Reducing end, Non-reducing end
① Reducing end : Terminal carbon at glucose’s position 1
② Non-reducing end : Terminal carbon at glucose’s position 4
③ Chain elongation through α 1→4 linkage, branch formation through α 1→6 linkage
④ Only one reducing end, but non-reducing end present in each branch
⑵ Oligosaccharides have multiple non-reducing ends and are non-reducing
⑶ Oligosaccharides refer to C3 ~ C12
4. Glycolipids
⑴ Structure : Attached to cell membrane phosphoric acid, exposed on the outer side of the cell membrane
⑵ Example 1: Teichoic acid
⑶ Example 2: LPS (endotoxin) : Causes blood clotting and fever
5. Glycoproteins
⑴ Structure : Attached to cell membrane proteins, exposed on the outer side of the cell membrane
⑵ Function : Buffering
⑶ Composition : Over 95% is carbohydrates
⑷ Type 1: Peptidoglycan
① Bacteria-specific oligosaccharides/polysaccharides, prevents hemolysis due to complement activation
② Alternating N-acetylglucosamine and N-acetylmuramic acid with β 1→4 linkage
③ Pentapeptide = (L)-alanine + (D)-glutamine + (L)-lysine + (D)-alanine + (D)-alanine
○ 5 amino acids present in N-acetylmuramic acid, connected by peptide bonds
○ Cross-linked by pentaglycine
○ Vancomycin inhibits this cross-linking by binding to (D)-Ala-(D)-Ala part
○ Origin of peptidoglycan
④ Gram-positive bacteria
○ Forms thick peptidoglycan layer through cross-linking of pentapeptides containing (L)-lysine and (D)-alanine
○ Transpeptidase : Enzyme responsible for cross-linking of pentapeptides
⑤ Gram-negative bacteria : Forms 2-layered peptidoglycan by directly connecting N-AG chain and N-AM chain
○ Not cross-linked by pentapeptide
⑥ Lysozyme
○ Hydrolytic enzyme found in saliva, tears, etc.
○ Breaks β glycosidic 1→4 linkage
○ Effective against both Gram-positive and Gram-negative bacteria
⑦ Penicillin : Irreversible inhibition of transpeptidase
○ Gram-positive bacteria more susceptible to penicillin than Gram-negative bacteria
○ Weak effect on Gram-negative bacteria with removed LPS
⑸ Type 2: Proteoglycan (mucopolysaccharide) : Acidic oligosaccharide covalently linked to poly-peptides
Figure 3. Proteoglycan
Figure 4. Aggrecans
① Proteoglycan = Hyaluronic acid + Aggrecans
② Aggrecans = GAG + Core protein + Link protein + Heparin
○ Similar concepts: biglycan, versican
③ Hyaluronic acid
○ Synthesized in the cell membrane, forms linear molecules, attaches to core protein
○ Highly viscous due to high water content
○ Presence in adult tissues: Embryonic development, wound healing, cartilage tissue, vitreous humor in eyes, umbilical cord
○ Enzyme for hyaluronic acid synthesis present in cell wall
○ Hydrolyzed by hyaluronidase: Mechanism for degradation of egg’s vitelline envelope by sperm’s acrosomal enzyme
○ Hyaluronic acid prescribed to elderly with insufficient synovial fluid in knees
○ 90% of wrinkle-improving products are hyaluronic acid derivatives
④ Glycosaminoglycans (GAG)
○ Hexosamine + uronic acid or galactose, generic term for the structure
○ Examples : Heparin, heparan sulfate, chondroitin sulfate, hyaluronic acid, keratin sulfate, dermatan sulfate
○ GAG chain variations occur in the Golgi apparatus
○ Examples : O-linked oligosaccharide attachment, sulfation, epimerization of D-glucuronic acid
⑤ Core protein
○ Synthesized in the rough endoplasmic reticulum, N-linked oligosaccharide attached
○ Sulfation of core protein attached to hyaluronic acid after 2nd glycosylation in Golgi apparatus
⑥ Sulfation : Synthesized with core protein, attaches indirectly to hyaluronic acid molecule through core protein
○ Highly negatively charged due to many sulfate groups
○ High water content due to negative charge, reduces external impact and increases viscosity
○ Examples : Cartilage, goblet cells
○ Type 1: Chondroitin sulfate
○ Type 2: Keratan sulfate : Cornea, cartilage, bone, hair, nails
○ Type 3: Dermatan sulfate
⑦ Heparin : Prevents blood coagulation in vascular endothelium
⑹ Type 3: Dysadherin
① Highly expressed in colon cancer tissues
② Binds with fibronectin to activate cancer cells
③ Promotes cancer metastasis
6. Carbohydrate Recognition Proteins
⑴ Lectin
① Binds to host’s oligosaccharides on E. coli pilus
② Also used as a vascular indicator
⑵ Selectin
① Transmembrane molecule expressed on white blood cells or endothelial cells
② Type of cell-cell adhesion molecule (CAM)
③ P-selectin
○ Adhesion protein acting as CAM on endothelial cell surface
○ Present on activated platelets and endothelial cells
○ Gold standard for measuring acute or chronic platelet activation
⑶ Hemagglutinin and Neuraminidase
① Hemagglutinin
○ Acts during invasion of host cell
○ Binds to sialic acid residues on oligosaccharide chains on host cell surface
○ Sialic acid is also called N-acetylneuraminic acid
○ Hydrophilic and coiled structure at pH 7.4, amphiphilic helical structure in acidic environment → promotes endocytosis
② Neuraminidase
○ Acts during release from host cell
○ Temporarily binds to sialic acid and hemagglutinin on host cell membrane of influenza virus progeny
○ Neuraminidase hydrolyzes temporary glycosidic bond
③ Influenza virus is classified based on hemagglutinin and neuraminidase types
○ Hemagglutinin exists from H1 to H16
○ Neuraminidase exists from N1 to N9
○ Virus classification in the form of H#N#
④ Tamiflu™ and Relenza™
○ Competitive inhibitors of neuraminidase, similar to sialic acid
○ Inhibit influenza virus proliferation
7. Carbohydrate Metabolism
⑶ Reducing sugar
① All monosaccharides are reducing sugars.
② All disaccharides, except for sucrose, are reducing sugars.
③ Polysaccharides are non-reducing sugars.
Input: 2019.01.24 19:57