2.6.1. Part 2 of 2 Collagen and Proteoglycan (Proteoglycan Only) Flashcards
Function of proteoglycans?
Mechanical resiliency
What provides for the mechanical resiliency?
Unique structure of the carbohydrates
What does proteoglycan fuse with and what does this give us?
When combined with collagen, forms “composite material” properties of the ECM
Structure of proteoglycan
Uronic acid + “-osamine” [amino sugar]
What structure determines the properties of proteoglycan?
Properties vary based on the type and amount of glycosaminoglycans present
What major monosaccharide units make up hyaluronate?
Glucoronic acid
N-Acetyl glucosamine
What major monosaccharide units make up Dermatan sulfate?
L-iduronate
N-Acetyl galactosamine 4-sulfate
What major monosaccharide units make up Chondroitin 6-sulfate?
Glucoronic acid
N-Acetyl galactosamine 6-sulfate
What major monosaccharide units make up Keratan sulfate?
Galactose
N-Acetyl glucosamine 6-sulfate
What major monosaccharide units make up Heparin
L-iduronate 2 sulfate
Glucosamine 6-sulfate
What are the 5 types of monosaccharides found in GAGs?
N-Acetyl glucosamine N-Acetyl-galactosamine Glucuronic acid Iduronic acid Galactose
What is the first step of proteoglycan synthesis?
Sugars are added to a protein, one at a time, with UDP sugars serving as the precursors.
What happens in proteoglycan synthesis after this step:
Sugars are added to a protein, one at a time, with UDP sugars serving as the precursors.
Two galactose residues are added, followed by a glucuronic acid and an N-acetylglucosamine
What happens in proteoglycan synthesis after these steps:
Sugars are added to a protein, one at a time, with UDP sugars serving as the precursors.
Two galactose residues are added, followed by a glucuronic acid and an N-acetylglucosamine
Subsequent additions occur by the alternating action of two enzymes that produce the repeating disaccharide units.
One adds GlcUA
One adds CalNAc
In proteoglycan synthesis, as the chain starts to grow, what groups are added and by what?
As the chain grows, sulfide groups are added by phosphoadenosine phosphosulfate (PAPS)
Also known as “active sulfate”
Hunter syndrome is caused by a deficiency in what?
iduronate sulfatase
Hurler Syndromeis caused by a deficiency in what?
L-iuronidase
Maroteaux-Lamy Syndrome is caused by a deficiency in what?
N-acetylgalactosamine sulfatase
Sandhoff disease is caused by a deficiency in what?
B-hexosaminidase A and B
Sly syndrome (MPS VII) is caused by a deficiency in what?
B-glucuronidase
What are characteristics, etiology, cause, and diagnosis method for Hurler syndrome?
Deficiency of a-L-iuronidase
Osmotically active polymers accumulate in many tissues
Diagnosis at 6-24; need to demonstrate enzyme deficiency in cultured fibroblasts from the patient
Characterized by developmental delays, mental retardation, coarse facial features with macroglossia, skeletal abnormalities and mental retardation
Palliative treatment
What is hyaluronic acid?
a glycosaminoglycan found in synovial fluid and cartilage
Hunters vs. Hurlers genetic pattern
Hunters: X-linked; Hurlers: autosomal recessive; MPSI resulting from the buildup of glycosaminoglycans
Mucopolysaccaridoses?
- generic name for diseases resulting from the accumulation of mucopolysaccharides
Glycosaminoglycan?
various disaccharide repeating units and usually occuring in proteoglycans
Order of the enzymes used to degrade proteoglycans
- Iduronate sulfatase
- a-L-iduronidase
- N-acetylgalactosamine-sulfatase
- B - Hexosaminidase A and B
- B - glucuronidase
