BMSC754 Biomedical Biochemistry: Glycosaminoglycans, Proteoglycans, and Glycoproteins

Flashcards covering the features, functions, synthesis, and degradation of glycosaminoglycans, proteoglycans, and glycoproteins from the BMSC754 Biomedical Biochemistry lecture.

What are Glycosaminoglycans (GAGs)?

Large, unbranched polysaccharide chains with repeating disaccharide units.

What are Proteoglycans (PGs)?

Core proteins with multiple GAGs attached.

What are Glycoproteins (GPs)?

Proteins with varying amounts of carbohydrates.

What two types of sugars make up the repeating disaccharide units of GAGs?

One acidic sugar and one N-acetylated amino sugar.

What are common acidic sugars found in GAGs?

D-glucuronic acid and L-iduronic acid.

What are common N-acetylated amino sugars found in GAGs?

N-acetylglucosamine and N-acetylgalactosamine.

What characteristic makes most GAGs highly negatively charged?

Sulfation.

Which GAG is an exception to the rule of containing an acidic sugar, instead containing galactose?

Keratan sulfate.

What conformation do GAGs typically adopt due to electrostatic repulsion?

Extended conformation.

How do GAGs contribute to the gel-like consistency of substances like synovial fluid?

They associate with lots of water.

Which GAG is an exception to the rule of being able to attach to proteins?

Hyaluronic acid.

Where are GAGs primarily found in the body?

Extracellular matrix (ECM), mucous, synovial fluid, cartilage, and vitreous humor (eye).

What is the most prevalent type of GAG found in cartilage, tendons, ligaments, and the aorta?

Chondroitin 4- & 6-sulfate (C4S, C6S).

Which GAG, found in the cornea and loose connective tissue, contains galactose and N-acetylglucosamine?

Keratan sulfates (KS I & II).

Which GAG, found in skin, blood vessels, and heart valves, contains L-Iduronic acid and N-acetylgalactosamine?

Dermatan sulfate.

Which GAG lacks sulfates, does not attach to proteins, and is found in synovial fluid and vitreous humor?

Hyaluronic acid (hyaluronan).

Which highly sulfated GAG is found intracellularly in mast cells and acts as an anticoagulant?

Heparin.

Which GAG, similar to heparin but with fewer sulfates, is found in the basement membrane?

Heparan sulfate.

Where does the synthesis of NAc sugars for GAGs occur?

In the Golgi.

What are the common functions of proteoglycans?

Associate with ECM proteins, bind growth factors/cytokines, provide structural support, aid in migration, and regulate diffusion in ECM.

Where is the core protein of a proteoglycan synthesized?

Rough Endoplasmic Reticulum (rER).

Where are GAGs added to the core protein during proteoglycan synthesis?

In the Golgi.

What is the sulfate donor for sulfation during proteoglycan synthesis?

3’-phosphoadenosyl-5’-phosphosulfate (PAPS).

Where does GAG degradation predominantly occur?

Lysosomes, after endocytosis.

What concept describes the sequential removal of sugars from the non-reducing end during GAG and glycoprotein oligosaccharide degradation?

The 'last on, first off' concept.

What are Mucopolysaccharidoses?

Hereditary disorders caused by the lack of acid hydrolase enzymes in lysosomes, leading to accumulation of GAGs.

What enzyme deficiency causes Hunter syndrome (MPS II)?

Iduronate sulfatase.

What enzyme deficiency causes Hurler syndrome (MPS I & II)?

alpha-L-Iduronidase.

How do glycoproteins generally compare to proteoglycans in terms of protein and carbohydrate content?

Glycoproteins have more protein than carbohydrate.

What is glycosylation?

The co-translational or post-translational enzyme-mediated addition of carbohydrates to proteins.

What are some functions of carbohydrates on glycoproteins?

Help with protein folding, enhance solubility, prevent denaturation, protect from degradation, and aid in subcellular targeting.

What is an N-linked glycoprotein?

A glycoprotein with carbohydrates attached to the asparagine amide side chain.

What is an O-linked glycoprotein?

A glycoprotein with carbohydrates attached to the serine or threonine hydroxyl side chain.

What determines a person's ABO blood group?

Genes encoding glycosyltransferases that add specific terminal sugars (GalNAc for A, galactose for B, or neither for O) to O-linked glycoproteins.

What lipid is required for N-linked glycoprotein synthesis?

Dolichol.

What is the consensus sequence for oligosaccharide transfer to asparagine in N-linked glycoproteins?

Asn-X-Ser/Thr.

What specific carbohydrate tag is required for lysosomal enzymes to be targeted correctly?

Mannose 6-phosphate (M6P).

Where is the Mannose 6-phosphate tag added to lysosomal enzymes?

In the Golgi.