① Glucose is classified as D-form or L-form based on the stereochemistry of the carbon furthest from the CHO group (the bottom carbon in the Fischer projection).

② In the standard Fischer projection, if the -OH group attached to the carbon furthest from the CHO group is oriented to the right (R-configuration), it is D-form; if oriented otherwise, it is L-form.

③ It only indicates the absolute configuration of one carbon and has no correlation with positive or negative optical rotation.

④ In living organisms, carbohydrates such as monosaccharides exist in the D-isomer form.

⑶ 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

⑷ 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 the type of sugar (indicated as ■) attached to the fucose which is attached to the surface of red blood cells.

○ 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

○ In animal cells, sialic acid is attached 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

④ Lactose intolerance

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 In polysaccharides, there is only one reducing end, but there are non-reducing ends at each branch.

⑵ Oligosaccharides are non-reducing sugars because they have many non-reducing ends.

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 (immune reaction)

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

○ Etymology of peptidoglycan

④ Gram-positive bacteria

○ Forms thick peptidoglycan layer through cross-linking of (L)-lysine and (D)-alanine in pentapeptides.

○ 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 where GAG is 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

○ Present in small amounts in adult tissue, but abundant in embryonic development, wound healing, cartilage tissue, vitreous humor in eyes, and 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

○ Modification in GAG chain occurs in the Golgi apparatus.

○ Examples: O-linked oligosaccharide attachment, sulfation, epimerization of D-glucuronic acid

⑤ Core protein

○ Synthesis and attachment of N-linked oligosaccharide occur in the rough endoplasmic reticulum.

○ In the Golgi apparatus, sulfation occurs through secondary glycosylation, where sulfates are attached to core proteins.

○ Core proteins are then connected to hyaluronic acid on the cell membrane.

⑥ Sulfation

○ Synthesized with core protein in cell, then attaches indirectly to hyaluronic acid molecule through core protein.

○ Because it is sulfate-rich and has many carboxyl groups, it carries a high negative charge.

○ Due to its negative charge, it retains a large amount of water, which helps to cushion external shocks and increase 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 epithelial cells

② A type of cell-cell adhesion molecule (CAM)

③ P-selectin

○ Adhesion protein acting as CAM on epithelial 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

○ Recognizes and binds to sialic acid residues on carbohydrate terminals on host cell surface.

○ Sialic acid is also called N-acetylneuraminic acid

○ At pH 7.4, it exhibits a hydrophilic, anionic coil structure, while in acidic environments, it adopts a hydrophobic helical structure, which promotes endosomal release (endosomal escape).

② Neuraminidase

○ Acts during release from host cell

○ During budding of animal influenza viruses, sialic acid on the host plasma membrane temporarily binds with hemagglutinin.

○ Neuraminidase then cleaves this temporary binding (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 can be classified in the form of H#N#.

④ Tamiflu™ (oseltamivir) and Relenza™

○ Competitive inhibitors of neuraminidase.

○ Similar to sialic acid.

○ Inhibit influenza virus proliferation

7. Carbohydrate Metabolism

⑴ Process Details

⑵ Glucose Synthesis

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

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Chapter 24. Carbohydrates

1. Monosaccharides