Glycoproteins and Proteoglycans X Flashcards
Glycoproteins - def
**
proteins that covalently attach carbohydrate chains EXCEPT polymers of repeating units
Carb chains - short, unbranched
varying amounts and concentrations of carb
Proteoglycans - def
**
polysaccahrides attached to core protein
can have as much as 95% carb
Carbohydrate - types
Simple sugars Modified suagars (like adding amino groups) Polysaccharides
Simple Sugars
monosaccharides
i.e. glucose, mannose, galactose
Modified sugars
principal = hexosamines (N added to C2)
Polymers
putting sugars linked with glycosidic bonds , Di-, Tri-, Oligo- and Poly- i.e. maltose, lactose put together by glycosyltransferases taken apart by glycosidades
Glycosylation
attaching carbs
not template driven
Can use N or O linkages
known N and O linkages
**
N-glycosyl to asparagine
O glycosyl to serine or theorine
O glycosyl to hydroxylysine
Glycolysation - functional impact
Increase protein solubility
guide protein folding
provide some protections from proteolytic degradation to the polypeptide backbone
+other regulation events
Glycosylation - critical for
Naturally occurring proteins in higher concentrations
Biopharmaceuticals
Blood Group Substances (naturally occurring protein)
Different carbohydrates recognized for blood group definition
aberrant glycosylation
Can affect whether substrate get recognized by enzyme
aberrant glycosylation patterns of proeints
can be analyzed and validates as potential biomarkers of disease
Biopharm - i.e.
Erythropoitein, Myozyme
degradation of glycoprotiens - pthwy
sugars removed from non-reducing end, by lysosomes.
Opposite of construction
Enzyme deficiency results in progressive accumulation of aspartylglucosamine in tissues, spinal fluid and urine
KNOW
I cell disease - a.k.a, def
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Mucolipidosis, Lysosomal Storage disorder with UDP-N-acetylglucosamine-I-phosphotransferase deficiency
*enzyme that puts sugar on glycoproteins
Mucolipidosis - physcial manifesations
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corenal clouding
short stature
umbilical hernias.
proteoglycans
carbs with protein core
high anionic charge - basophilic (blue)
disaccharide repeating unit + sulfate (negative charge)
GAG - a.k.a, types
**
**glycosaminoglycans
Chonroitin Sulfate (most commoon, i.e. aggrecan)
Dermatan Sulfate
Hepran Sulfate
Keretan Sulfate
Heparin (huge clusters of negative charge = coagulant)
Hyaluronic acid
Disaccharide repeating unit
uronic acid and amino sugar
negative charge
Aggrecan loss from the cartilage ECM is an early and sustained feature of OA
KNOW
Proteoglycans - role
**
support/connective tissue
mechanical
diffusion
Proteoglycans - location
intracellular compartment, cell surface or in ECM
Classes of Proteoglycans
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Large aggregating proteoglycans *(i.e.AGGRECAN)
small leucine-rich proteoglycans (SLRP)
basement membrane proteoglycans
Hyaluronate/Hyaluronic Acid - def, fxn
GAG - not proteoglycan
co ploymer of Nacetyleglucoamine and Glucuronic Acid
shock absorgber, lubricant
Heparin
unlike other GAG’s, intracelluar component of mast cell
used to contract thrombosis(clot)
Lubricin
Major lube in joint - boundary lubricant
degradation of proteoglycans
one at a time
Mucopolysaccharidoses - def
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genetic disorder of excessive accumulation and excretion of the oligosaccharides of proteoglycans
Mucopolysaccharidoses - i.e.
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Hunter
Hurler + Scheie
Hunter - Accumulated products, Deficient enzyme, cleaves
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Accumulated products - heparin sulfate, dermatan sulfate
Deficient enzyme - Iduronate sufatase
*cleaves sulfate from hylauronic acid
Hurlers + Scheie - Accumulated products, Deficient enzyme, cleaves
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Accumulated products - heparin sulfate, dermatan sulfate
Deficient enzyme - alpha-L-Iduronidase
*Cleaves hylauronic acid
