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:<3: Saliva :<3: (Organic (9) Components (Histatins (Function…

- - - - High Molecular weight glycoproteins containing O- and N- linked sugars [GlcNAc/GalNAc] - N are much less abundant
        
        "Pentasaccharide" core structure in N-linked sugars
        
        3 Mannose residues, with 2 N-Acetlyglucosamine (GlcNAc) residues attached in a T-shape.
        
        up to 80% carbohydrate by weight.
        
        make up over 25% of salivary protein
        
        sugars linked by enzymes in ER/Golgi - an example of post-translation modification
        
        Consensus sequence: Asn only added 2 places before Ser/Thr
    - - MG1
        
        mixture of 3 gene products
        
        Oligomeric; Mr > 1MDa
        
        Produced in diff amounts by major and minor glands
        
        Forms complexes with other salivary components (PRPs, amylase, statherin, histatins and anti-microbial peptides)
      - MG2
        
        Derives from a single gene
        
        Single monomer
        
        Produced in diff amounts by major and minor glands
        
        Binds oral pathogens and yeast (candida)
    - - direction of microbial colonisation
      - provide a barrier to microbial colonisation
      - lubrication of hard and soft tissues to protect from mechanical damage
      - Protection of oral surfaces from dessication
      - Anti-microbial / Anti-fungal activity
    - - HALF of amino acids are Ser/Thr
      - Cysteine residues can form Sulphydryl [-SS-] bonds with adjacent monomers.
      - This allows mucin to form oligomers (in MG1)
  - - - Rich in proline
      - Small Mr: under 5KDa
      - High -ve charge asymmetrically distributed
      - produced by acinar cells
      - Has 2 sites for binding to HAP
    - - Inhibits spontaneous precipitation of calcium to prevent ectopic calcification
      - inhibits secondary growth of HAP. (res 1-6)
      - Important component of the salivary pellicle
  - - - comprises up to 40% of salivary protein
      - conc = 50mg/100mL
      - high -ve charge at carboxyl terminal -> acidic
      - PRP 1-6 share sequence homology
      - Strongly adsorbed to HAP
      - Rich in Proline (40%)
    - - Amino terminal binds to oral microbe
      - Inhibit HAP Growth (via amino terminal)
      - Carboxyl terminal interacts with cell walls
      - Selectively excludes pathogens
  - - - Potent inhibitor of Candida albicans/ somewhat mutans
      - Potench a buffer due to pK of ring close to neutral
  - - - Function:
        
        break down long glucose polymers with no need for catalysis.
        
        Catalyses hydrolytic cleavage of a1-4 glycosidic linkage (not 1-2)
        
        CHO digestion
      - Properties:
        
        Binds to HAP and some microbes
        
        cannot break down complex polysaccharides found in dental plaque (sucrose)
        
        Ca2+ dependent and Cl- activated
        
        accounts for 1/3 of the parotids salivary protein
    - - Originated from the striated duct
      - Function:
        
        works with sIgA to lyse cells that are already tagged with sIgA; increased specificity of the lysozyme.
        
        hydrolyses a1-3 linkage between N-acetylmuramic and N-acetylglucosamine in bacterial cell walls.
    - - Mr = 80 KDa appx.
      - Important that it removes H2O2 to prevent free radicala formation which can damage soft tissue.
      - Hypothiocyanite is antibacterial as its toxic due to the inhibition of metabollic enzymes,
      - Catalyses conversion of peroxide (bacterial metabolism) and thiocyanite (diet) to Hypothiocyanite.
  - - - Secreted by gland epithelium
      - Dimer.
      - Most abundant Ig
      - Acquires a secretory glycoprotein component; confers protection in the hostile oral environment [sIgA]
    - - arise when inflammation causes the GCF to exude from the gingival crevice.
      - IgM - Pentamer
      - Found in GCF
      - IgG - gamma chain
  - - - Metabolised by bacteria to produce ammonia
      - Sialin = GLY-GLY-LYS-ARG
- - - - Rampant Caries
      - Periodontal disease
      - Desiccation and rapid destruction of mucosal surfaces
    - - Medications [ Over 500 drugs can causes Xero. ]
        
        Elderly especially at risk because taking multiple drugs can have a cumulative effect to exacerbate XERO.
      - Cancer therapies
        
        Radiation Therapy: Salivary glands sensitive to therapy used for head and neck cancers; serous more so than mucous. severity increases with dose and rarely fully recovers
        
        Chemotherapy: changes the flow rate and compostion directly; immunosuppression causes Ig's in saliva to fall and exacerbate XERO
      - Sjorgren's Syndrome [ Autoimmune disease leading to parotid and submaxillary gland dysfunction ]
        
        Primary: not associated with any other autoimmune disease
        
        Secondary: associated with other autoimmune diseases such as rheumatoid arthritis / Lupus
    - - Sugar free gum (mechanical) or sugar free sweets (gustatory)
      - Artificial salivary substitutes; can be uncomfortable and have low compliance
      - Water-based gels to relive symptoms for hours at a time
      - Medication: Cholinergic agonists that give parasympathetic stimulation (useful for SS)
  - - - Control of bacteria and fungi
      - Digestion
      - Eating, swallowing, mastication
      - Protect / repair mucosa
      - Speech
      - Protect / repair dentition
      - Airway Maintenance
    - - .
        
        MECHANISM
        
        antibacterials and lubrication
        
        Mucin film / growth factors
        
        Lubircation
        
        Calcium and phosphate, pellicle proteins, fluoride
        
        Antibacterials / water retaining glycoproteins
        
        Antibacterial, Igs, lactoferrin, lysozyme, histatin
        
        Amylase
  - - - Circadian Rhythm
      - Age
      - Health
      - Medication
  - - - Causes site specific retention / clearance AND limited transfer across the mouth.
        
        Sites with most clearance (in order) :
        
        Tongue
        
        Upper buccal sulcus
        
        Lower labial sulcus
        
        Lower buccal sulcus
        
        Upper Labial sulcus
        
        Significance:
        
        Sugar (substrate) clearance and retention
        
        Fluoride (therapeutics) clearance and retention
        
        Positioning of slow release devices e.g. Ionomers (GIC)
  - - - Nature of sample (site / gland specific)
        
        Site: pre-weighed filter paper dabbed onto surface then saliva eluded from the sample using a buffer.
        
        Gland: Curby cup placed over the opening to the parotid gland next to U7 buccal.
      - Time of day (circadian rhythm)
      - Nature of stimulant
      - Flow rate
      - Method of collection
    - - Loss of enzyme activity
      - Loss of CO2 -> change in pH
      - Proteins denature
- - - - Maintaining the ionic product for HAP
      - Isoelectric point for the precipitation of salivary proteins on tooth surfaces
      - Create the optimum pH for salivary enzymes
    - - CHO metabolism by plaque microbes causes pH to fall; falls rapidly and restores slowly
      - HAP dissolves below pH 5.5 = critical pH
      - pH restored by salivary buffering, remineralisation occurs when pH is above critical (circa 30mins)
    - - Higher sucrose concentration causes pH to fall LOWER but NOT any QUICKER
  - - - <1 mM (unstim.) 60mM (high stim.)
      - Mechanically stimulated saliva = 15mM
    - - Carbonic anhydrasepresent in glands/saliva
      - H+ ⇌ HCO3- ⇌ H2CO3 ⇌ H2O + CO2
      - pKa = 6.1 (HCO3- = H2CO3)
      - generates H2CO3 in backward direction, thus increasing HCO3-
    - - GLAND:
        
        Catabolism creates CO2
        
        Carbonic anhydrase combines CO2 and water to H2CO3
        
        HCO3- produced when [H2CO3] increases
      - PLASMA
        
        [CO2] varies due to respiration
        
        resultant [HCO3-] at equilibrium with plasma at 1.3mM
  - - - K+ -> Phosphate [14-32]
      - Na+ -> HCO3- [6-26]
  - - - Can be increasingly protonated at lower pH up to H3PO4
      - PO4--- // HPO4-- // H2PO4- // H3PO4
      - pKa......... 12.7 ------- 7.2 -------- 2.12----------
  - - - Ca10 (PO4)6 (OH)2 -> ionic product is the same but split into ions
      - -> HAP spontaneously dissolves when PO4--- / Ca++ levels drop
        
        -> Excess Ca++ / PO4--- causes calculus deposits or salivary gland stones blocking ducts.
        
        -> When [Ca++/PO4---] causes precipitation, soln. is saturated with respect to HAP.
        
        -> above this is SUPERSATURATED.
        
        -> Saliva is supersaturated with respect to HAP at neutral pH
      - "it is a salt of calcium phospahate"
      - Other Calcium phosphate salts:
        
        Dicalcium phosphate >> DCPD >> CaHPO4
        
        Tricalcium phosphate >> TCP >> Ca3 (PO4)2
        
        Monocalcium phosphate >> MCP >> Ca (H2PO4)2
- - - - Addison's Disease: Lack of aldosterone secretion causes high levels of Na+ in saliva.
      - Na+ depleted animals have more aldosterone and less Na+ in saliva - viceversa for Na+ replete.
- - - - Pressure
      - Nausea
      - Smell + Taste
      - Conditioned reflexes
    - - Fatigue
      - Sleep
      - Dehydration