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GAGS:

• 
• GAGS: made up of multiple disaccharide units forming a polysaccharide unbranched chain, negatively charged.
• -disaccharide: composed of:
• 1)amino sugar(D-glucosamine OR D-Galactosamine-> in which amino group is usually acetylated that eliminates its positive charge.
• ->the amino sugar may also be sulfated
• 2)Acidic sugar:(D-glucoronic acid/L-iduronic acid)
• ->these will give it a negative charge that will cause an overall STRONG negative force

FUNCTION OF GAGS:

• (See Lippin page158)
• RELATIONSHIP OF GAGS STRUCTURE & FUNCTION:
• gags negativity causes a strong repulsive force which makes all GAGS separate from eachother and extended in solution.
• ->compression of these GAGS causes water to move out and releasing these GAGS causes water to shift inside (eg: this property contributes to the resilience of synovial fluid and vitrous humor)
• ->this repulsive force is like magnets and is also responsible for the slippery nature of GAGS (eg: mucus is slippery)
• ->ALSO cause cell to cell signalling and adhesion

TYPES OF GAGS:

• 
• (SEE REGISTER also)
• *Only non-sulfated GAG: hyaluronic acid (MAIN FUNCTION: LUBRICANT &SHOCK ABSORBER)
• *ALL: are covalently attached to protein to form proteoglycans EXCEPT: hyaluronic acid but ALL proteoglycan monomers associate with hyaluronic acid to form: PROTEOGLYCAN AGGREGATES.
• KERATAN SULFATE: has galactoseis present inpalace of acidic sugar

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SYNTHESIS & DEGRADATION of GAGS

• synthesized IN GOLGI APPARATUS
• POLYSACCHARIDE chains are elongated by the sequential adding of alternating acidic and amino sugars--> donated by: their UDP derivatives
• LAST STEP: sulfation if need be according to GAG (SOURCE OF SULFATE: 3-phosphoadenosyl-5'-phosphosulfate)
• DEGRADATION:
• in lysosomes (by LYSOSOMAL HYDROLASES)
• FIRST: broken down to oligosaccharide
• DEFICIENCY OF THIS HYDROLASE--> MUCOPOLYSACHARIDOSES (GAGS will accumulate in tissues eg; skeletal and ECM deformities and mental retardation) eg: HUNTER, HURLER, MORQUIO, SANFILLIPO SYNDROME)

SYNTHESIS CYCLE

PATHOLOGIES of GAGS

PROTEOGLYCANS:

• Have a "BRUSH BORDER" appearance
• composed of a core protein which is linked to GAGS
• multiple such proteoglycan monomers are brought together and linked by means of hyaluronic acid to form PROTEOGLYCAN AGGREGATES
• 

GLYCOPROTEINS:

• 
• Proteins to which oligosachharides are covalently attached. Length of sugar chain is usually short (2 to 20 residues) usually variable(eg: IgG: 4%carbs & mucin contains: >80% carbs), branched (differeing it from GAGS), may or may not contain negative charge)
• FUNCTIONS:
• cell surface recognition (by other cells, hormones, viruses) & cell surface antigenicity (eg: blood group)
• as component of ECM (laminin, fibronectin: adhesive glycoproteins. chondronectin and osteonectin: in cartilage and bones respectively)
• as component of mucin in GIT and Urinary tract
• almost all GLOBULAR PROTEINS in plasma: (albumin, globulin, igG, etc)

SYNTHESIS & DEGRADATION:

• synthesized in ER, and Golgi
• precursors: nucleotide sugars
• I-CELL DISEASE: inabiltiy to transfer glycoprotein to lysosomes b/c of defieciency of enzyme that phosphorylates mannose)
• Degradation by lysosomes by acid hydrolases
• deficiency of these enzymes: causes--> oligosaccharidosis--> glycoprotein storage disease

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• Mnemonics:
• Type I: BONE |
• Type II: carTWOlage.
• Type III: ArTHREE (Artery).
• Type IV: Under the floor (basement membrane)