Proteoglycans, Glycosaminoglycans, and Glycoproteins

Glycosaminoglycans (GAGs)

• There are at least seven GAGs:
  • Hyaluronic acid (hyaluronan)
  • Chondroitin sulfate
  • Keratan sulfate I
  • Keratan sulfate II
  • Heparin
  • Heparan sulfate
  • Dermatan sulfate

Glycoproteins

• Glycoproteins are proteins containing branched or unbranched oligosaccharide chains, including fucose.
• Carbohydrate (oligosaccharide chains or glycans) is covalently bound to amino acids; glycosylation is the most frequent posttranslational modification of proteins.
• They occur in cell membranes and many proteins are glycosylated.
• Sialic acids are N- or O- acyl derivatives of neuraminic acid, a nine-carbon sugar derived from mannosamine and pyruvate.
• Sialic acids are constituents of both glycoproteins and gangliosides.
• Examples of glycoproteins include:
  • Immunoglobulins (antibodies)
  • Certain hormones, such as:
    • Follicle-stimulating hormone (FSH)
    • Luteinizing hormone (LH)
    • Thyroid-stimulating hormone (TSH)

Introduction to Carbohydrates

• Carbohydrates (saccharides) are the most abundant organic molecules in nature and are widely distributed in plants and animals.
• They have important structural and metabolic roles, providing a significant fraction of dietary calories for most organisms.
• They act as a storage form of energy in the body and serve as cell membrane components that mediate some forms of intercellular communication.
• They serve as a structural component of many organisms, including the cell walls of bacteria, the exoskeleton of insects, and the fibrous cellulose of plants.

Glucose

• Glucose is the most important carbohydrate; most dietary carbohydrate is absorbed into the bloodstream as glucose.
• Other sugars are converted to glucose in the liver.
• Glucose is the major metabolic fuel of mammals and is a precursor for the synthesis of all other carbohydrates in the body, including:
  • Glycogen for storage
  • Ribose and deoxyribose in nucleic acids (DNA and RNA)
  • Galactose for synthesis of lactose in milk, in glycolipids, and in combination with protein in glycoproteins and proteoglycans.

Diseases Associated with Carbohydrate Metabolism

• Diabetes mellitus
• Galactosemia
• Glycogen storage diseases
• Lactose intolerance

The Glycome

• The glycome is the entire complement of sugars produced by an organism, whether free or in more complex molecules.

Classification of Carbohydrates

• Monosaccharides
• Epimers: isomers differing as a result of variations in configuration of the -OH and -H on carbon atoms 2, 3, and 4 of glucose.
• Aldose-ketose isomerism: chemically, aldoses are reducing compounds, and are sometimes known as reducing sugars.

Physiological Importance of Monosaccharides

• Derivatives of trioses, tetroses, and pentoses and of the seven-carbon sugar sedoheptulose are formed as metabolic intermediates in glycolysis and the pentose phosphate pathway.
• Carboxylic acid derivatives of glucose are important, including:
  • D-glucuronate (for glucuronide formation and in glycosaminoglycans)
  • L-iduronate (in glycosaminoglycans)
  • L-gulonate (an intermediate in the uronic acid pathway)

Glycosides

• Glycosides are formed by condensation between the hydroxyl group of the anomeric carbon of a monosaccharide and a second compound that may be another monosaccharide or, in the case of an aglycone, not a sugar.
• Examples of glycosides include:
  • Digoxin, an inhibitor of the Na+–K+-ATPase of cell membranes
  • Ouabain
  • Other glycosides include antibiotics such as streptomycin.

Deoxy Sugars

• Deoxy sugars are those in which one hydroxyl group has been replaced by hydrogen; an example is deoxyribose in DNA.

Amino Sugars (Hexosamines)

• Amino sugars are components of glycoproteins, gangliosides, and glycosaminoglycans.
• Examples of amino sugars include:
  • D-glucosamine, a constituent of hyaluronic acid
  • D-galactosamine (also known as chondrosamine), a constituent of chondroitin
  • Erythromycin, an antibiotic containing amino sugars

Disaccharides

• Disaccharides are sugars composed of two monosaccharide residues linked by a glycoside bond.
• Physiologically important disaccharides include:
  • Maltose
  • Sucrose
  • Lactose

Quick View of Carbohydrates

• Carbohydrate polymers called glycans (polysaccharides) serve as structural and protective elements in the cell walls of bacteria, fungi, and plants, and in the connective tissues of animals.
• Other carbohydrate polymers lubricate skeletal joints and participate in cell-cell recognition and adhesion.
• Most hexoses of living organisms are D isomers.
• Storage of low molecular weight metabolites in polymeric form avoids the very high osmolarity that would result from storing them as individual monomers.

Polysaccharides

• Inulin is a polysaccharide of fructose (a fructosan) found in tubers and roots of dahlias, artichokes, and dandelions.
• Cellulose is the chief constituent of plant cell walls, consisting of β-D-glucopyranose units linked by β1 → 4 bonds.
• Chitin is a structural polysaccharide in the exoskeleton of crustaceans and insects, and also in mushrooms.
• Pectin occurs in fruits.

Glycemic Index

• The glycemic index of a starchy food is a measure of its digestibility, based on the extent to which it raises the blood glucose concentration compared with an equivalent amount of glucose or a reference food.

Glycoconjugates: Proteoglycans, Glycoproteins, and Glycolipids

• On almost every eukaryotic cell, specific oligosaccharide chains attached to components of the plasma membrane form a carbohydrate layer (the glycocalyx), that serves as an information-rich surface that the cell shows to its surroundings.