CHEM 130A: glycans and glyconjugates

What are polysaccharides and average weight?

large chains of monosaccharides of ~20,000 kDa, but there is no defined molecular weight

What is a homopolysaccharide and heteropolysaccharide? What is an unbranched vs. branched polysaccharide?

homoplysaccharide: contains a single sugar species

heteropolysaccharide: contains multiple types of sugar monomers

unbranched: monomers all on same linkage

branched: monomers on different linkages

What are storage glycans and its two main types?

storage glycans are long polysaccharides that store D-glucose to use as energy later. The two main types are starch and glycogen

What are the main types of starch? Include their glycan nomenclature, glycosidic linkage name, general structure, and where are they found.

amylose

• unbranched D-glucose with α1→4 linkages

• range of 1,000 to 1 million glucose units

amylopectin

• highly branced D-glucose with α1→4 linkages and α1→6 branches

Both types

• helical structure to satisfy H-bonding demands of OH group without relying on H₂O

• found in plants

What is glycogen? Include its glycan nomenclature, glycosidic linkage name, general structure, and where are they found. What is osmotic tension?

• very highly branched (more than amylopectin) with α1→4 linkages and α1→6 branches

• found in muscle and liver of animals, with 7% of liver weight being glycogen

• osmotic tension: polymers satisfy H-bonding demands of the OH groups through the neighboring glucose molecules, without having to pull water into the cell

What is the significance of the amylose helix with respect to H-bonding?

the OH groups along the glucose monomers form H-bonds with other OH groups along the helix chain

→ pulls α1→4 glucose chains into tight, stable left-handed helix

→ this helical structure minimizes water interactions

What are structural glycans and its two main types?

structural glycans are polysaccharides that provide structure to cells and tissues. The two main types are cellulose and peptidoglycan

What is cellulose? Include its glycan nomenclature, glycosidic linkage name, general structure, and where are they found/used. How does cellulose related to humans vs. cows?

• linear, unbranched D-glucose with β1→4 linkages

• found in plants and used in cardboard, cotton, and insultion

• humans lack enzymes to break β1→4 linkages, therefore cannot digest cellulose to liberate free glucose. Cows’ microbiome contains the cellulase enzyme, therefore can digest cellulose to liberate free glucose

What is peptidoglycan? Include its glycan nomenclature, what it is composed of (two main parts), glycosidic linkage name, and where are they found/used.

• heteropolysaccharide composed of GlcNA/NAG and Mur2Ac/NAM

• GlcNA/NAG and Mur2Ac/NAM are joined by β1→4 linkages, and cross-linked with short peptide chains

  • lysozyme: breaks bond between GlcNA/NAG and Mur2Ac/NAM

• found in secretions (e.g., tears, saliva, and mucus) and used in antibiotics to inhibit bacterial cell wall construction (e.g., penicillin antibiotic prevents peptidogylcan synthesis)

What is glycosaminoglycans (GAGs)? Include where are they found/used.

• linear polymers of repeating disaccharide units with strong (-) charges that repel to form extended tight helices

• found in extracellular matrix of bacteria and animals

• uses

  • tissues: viscosity, adhesion, and tension

  • hyaluronan: skincare for the skin’s structure and hydration

  • glucosamine: joint-support supplements (e.g., chondroitin 4-sulfate)

  • anticoagulant: natural blood thinner (e.g., heparin)

What are the four main types of glycoconjugates? Define each

1) proteoglycans: mostly glycans and a little protein

2) glycoproteins: mostly proteins and a little glycan

3) glycome: cell surface formed by proteoglycans and glycoproteins

4) glycolipids: lipids covalently bonded to carbs and essential for cell structure and recognition

What are proteoglycan? Include an example.

What are the two glycoconjugates associated with proteoglycan? Define them.

How does a GAG attach to a protein?

Proteoglycans are specialized glycoconjugates called glycosaminoglycans (GAGs) attached to proteins located on the cell surface (e.g., heparain sulfate and chondrotin sulfate attached to the serine protein residue).

The glycoconjugates associated with proteoglycan are glycoproteins and glycosphingolipids.

• glycoproteins: mostly protein with a little glycan (e.g., N-glycan attached to Asn residue, and O-glycan attached to Ser/Thr residues).

• glycosphingolipids: lipids attached to cell membrane

GAGs attach to proteins through…

1. specific amino acid sequence on core protein (e.g., Ser)

2. specific 4-sugar linker sequence (e.g., GlcA → Gal → Gal → Xyl)

3. repeating GAG connected by glycosidic linkages (e.g., (GlcA → GalNAc4S)_n with β1→3 and β1→4 linkages)

What are glycoproteins?

What is the importance of linkages in respect to glycoproteins? How long are glycan chains typically?

What is O-linked glycosylation vs. N-linked glycosylation?

Explain the 3-step process of N-linked glycosylation of secreted proteins? What is the exception with O-linked glycosylation?

Glycoproteins are mostly proteins and a little glycan, and are located intracellularly or extracellularly.

For linkages, ½ of all proteins are glycosylated. Sugar molecules (e.g., carbs) are covalently attached to specific amino acids on a protein chain. Glycan chains are typically ~20-30 sugars long, or 1 sugar long.

O-linked glycosylation: anomeric C attached to OH group of Ser/Thr. N-linked glycosylation anomeric C attached to N group fo Asn via amide bond.

N-linked glycosylation process

1. RER: enzymes do N-linked glycosylation

2. golgi apparatus: as proteins move through pathway, O-linked glycosylation and editing of N-linked glycosylation happens

3. secretory vesicle: finalized glycoproteins are packaged for exocytosis to happen

Exception with O-linked glycosylation: NA

What are glycolipids? Define.

What are the two main types of glycolipids? Define and give an example of each.

Glycolipids are lipids convalently bonded to carbs and are essential for cell structure and recognition.

Gangliosides: cell membrane lipids covalently bound to sugar.

• Ex: blood type

  • A- and/or B-enzymes grab a sugar (GlcNAc and/or galactose)

  • GlcNAc and/or galactose (sugar) is bound to H-antigen (base sugar chain)

  • binding creates A- and/or B-antigen, determining blood type (A, B, AB, or O)

Lipopolysaccharides: lipids that form outer membrane of gram negative bacteria

• regions: lipid A (attached to membrane), core, and O-specific chain (outermost sugar)

• help define bacterial strains

What are three diseases of glycosylation? Explain each.

Hereditary multiple exotoses: genetic inability to make the GAG heparan sulfate, leading to osteosarcoma and cancer.

Cancer cells: cellular changes in glycosylation patterns to evade the immune system.

SARS-CoV2 spike protein: protein is heavily glycosylated, hiding its antigens from antibodies and protease enzymes.