Glycosaminoglycans, Proteoglycans, and Glycoproteins

compare and contrast the features of glycosaminoglycans, proteoglycans, and glycoproteins

Glycosaminoglycans (GAGs): large unbranched polysaccharide chains with repeating disaccharides

Proteoglycans (PGs): Core protein with multiple GAGs

Glycoproteins (GPs): proteins with varying amounts of carbohydrates

what is the function of glycosaminoglycans (GAGs)

can be attached to proteins (except hyaluronic acid), structural support, cell hydration, involved in cell signaling, adhesion and wound repair

what are the 6 different types of glycosaminoglycans based on carbohydrate composition

Chondroitin 4-/6- SO4

Keratan sulfates (KS I/II)

Dermatan sulfate

Hyaluronic acid (hyaluronan)

Heparin

Heparan sulfate

Where in the body is GAG Chondroitin located

cartilage, tendon, ligaments and aorta

Where in the body is GAG Heparan sulfate located

basement membrane

Where in the body is GAG Heparin located and what makes it different from other GAGs

Highly sulfated and anticoagulant

Intracellular mast cells

Where in the body is GAG Hyaluronan (hyaluronic acid) located and what makes it different from other GAGs (pink text in lecture)

No sulfates, No attachment to proteins, found in bacteria

Synovial fluid, vitreous humor, cartilage, and loose connective tissue

Where in the body is GAG Dermatan sulfate located

skin, blood vessels, and heart valves

Where in the body is GAG Keratan sulfates I and II located

KS I: cornea

KS II: loose connective tissues

In general terms describe GAG synthesis of acidic sugars

Glucose 1-P04 + UTP → UDP-Glucose

oxidation occurs

after incorporation Epimerization (L-iduronic acid) 

what cellular component performs degradation of GAGs

lysosomes

In general terms, describe GAG synthesis of N-acetylated amino (NAc) sugars 

Requires glutamine to go through 4 steps

1. Acetylation

2. Isomerization

3. Activation

4. Epimerization

where does GAG synthesis of NAc sugars occur, and the precursor

in Golgi

Precursor: F-6-PO4

in general terms describe GAG degradation

after endocytosis, lysosomes, multiple enzymes (like acid hydrolases) are involved

what are the 3 types of acid hydrolases (enzymes) are involved in GAG degradation and their function

Endoglycosidases: cleave within chains

Exoglycosidases: cleave at end of chain

Sulfatases: remove sulfates

what is GAG synthesis and degradation “last on, first off” concept

order in which GAGs are broken down within lysosomes, where the groups added last during GAG synthesis are the first ones to be removed during degradation

Explain proteoglycan synthesis

core protein→ GAG addition→ linker synthesis of O-link with Serine residue→ alternating addition of acidic and amino sugars, → sulfation with sulfotransferase of PAPS after carbohydrate addition

what does PAPS stand for (type of SO4 donor)

3’-phosphoadenosyl-5’-phosphosulfate

what is the function of Proteoglycans (PGs)

Associate with ECM proteins

bind growth factors, cytokines

structural support 

migration

diffusion in ECM

where does proteoglycan synthesis occur in a cell

rER for core protein

Golgi for GAG addition

What occurs/ steps in GP synthesis

protein synthesis on rER and where initial carbohydrate addition begins

activated sugars

in GP synthesis what plays a role in glycosylation

protein structure

what are some activated sugars involved in GP synthesis

UDP-glucose

UDP-galactose

UDP-GlucoseNAc

UDP-GalactoseNAc

Which genes encode glycosyltransferases in the A, B, O groups of blood

A: terminal GalNAc

B: terminal galactose

O: neither

what type of GP sugar protein link is present in ABO blood groups

O-linked

what is GP, sugar protein N-linked

asparagine amide side chain

involved in membrane & secreted proteins

which GP sugar protein link has no consensus sequence

O-linked

which GP sugar protein link has high mannose

N-linked

which GP sugar protein link is complex

N-linked

Which GP sugar protein link has a variety of sugars

O-linked

what is GP sugar protein O-linked

serine/threonine hydroxyl side chain

involved in mucous fluids, membrane & secreted proteins

what components/steps are involved in N-linked GP synthesis

requirement of dolichol where 14 sugar oligosaccharides are added to it via PP link, which is then transferred to Asn on protein, that ends at the golgi

in N-linked GP synthesis, what type of GP is processed and unprocessed in the golgi

Processed: complex GP

Unprocessed: High mannose GP

what is an example of a consensus sequence involved in N-linked GP synthesis

Asn-X-Ser/Thr

which GP synthesis requires the lipid dolicchol

N-linked synthesis

what happens in GP O-linked synthesis and where does it occur in the cell

Addition of GalNAc to Ser/Thr

Additional sugars added in the golgi with glycosyltransferases

where does N-linked GP synthesis occur in the cell

Lumen rER

what is the importance of mannose 6-phosphate

Acts as a tag and is crucial for directing proteins to lysosomes, ensuring that waste degrading enzymes are correctly delivered to the lysosomes

where is the mannose 6-PO4 tag added in the cell

Golgi

what lysosomal enzyme is involved with GPs

GluNAc phosphotransferase

what is the function of Glycoproteins

cell recognition/adhesion, and signal transduction