Metabolism of human lens .pptx

Metabolism of human lens .pptx

• 2.
  In the lensthe biological energy necessary for the maintenance of the transparency ,synthesis, and ,repair .
• 3.
  HARDING AND CRABBE(1984) CHANG AND CHYLACK(1985)
• 4.
  The avascular lensrelies on the aqueous humor as the major source of the oxygen , glucose , and other nutrients needed to support its normal metabolic activity.
• 5.
   CONTINUOUS SUPPLYOF ATP REQUIRED FOR: 1. Active transport of ions and aminoacids 2. Maintenance of lens dehydration 3. Lens transparency 4. Continuous protein synthesis 5. GSH synthesis MAJOR SITE: epithelium
• 7.
   Glucose isvery essential for the normal working of the lens.  Lens can survive under incubation condition in the absence of oxygen ,so long as an adequate supply of glucose is available. (but not if provided with oxygen only)
• 8.
  Glucose from theaqueous and vitreous diffuses into the lens and is rapidly metabolized. Glucose is rapidly metabolized through four main pathways: 1) Anaerobic glycolysis 2) Krebs cycle(oxidative) 3) Hexose monophosphate shunt 4) Sorbitol pathway
• 9.
   It isnot as efficient as the aerobic process.  But obviates the problem of oxygen starvation in a tissue  About 85% of lens glucose is metabolized through this process  ENZYMES: hexokinase & phosphofructokinase  END PRODUCT: lactic acid  1 mole of glucose gives 2 moles of ATP
• 10.
   1 moleof glucose gives 36 moles of ATP  Limited to epithelium  Only 3% of lens glucose metabolized by this pathway  But generates upto 20% of total ATP needs for lens
• 11.
  It uses glucose-6-phosphate as its initial substrate and does not generate any ATP. It forms pentose and NADPH PENTOSE is utilized for RNA synthesis and some of it is re-enters into the glycolytic pathway NADPH is to maintain lens glutathione in reduced state and also neccessory factor in sorbitol pathway
• 12.
   5% ofglucose used by the lens is metabolized by this pathway  It does not generate any ATP  Hence , this pathway has received wide attention mainly because of its pivotal role in the development of sugar cataract.  When sorbitol accumulates within the cells of lens,it sets up an osmotic gradient that induces influx of water and lens swelling , and ultimate loss of lens transparency  Discovered by van heyningen (1959)
• 15.
   PROTIEN SYSTHESIS:These are synthesized from free amino acids which are actively transported into the lens from aqueous .  Site :epithelium and peripheral cortex  PROTIEN BREAKDOWN: in the lens it is catalyzed by enzyme peptides and proteases.
• 17.
   GSH inthe lens is to maintain the thiol(SH) groups of proteins in the reduced state ,thus prevents HMW protein aggregates.  Helps in regulate cation transport and permeability.  Protects against oxidative damage to lens  Its metabolism involves in detoxification of H2O2 which is generally present in aqueous humor.  GST-detoxification  Almost 12% of total ATP formed by the lens is utilized for the GSH synthesis  Enzymes : -glutamyltransferase & 5-prolinase  Oxidative form—GSSG(glutathione disulphide)  Reduced form--GSH 𝜸
• 18.
  [1] Berman ER.Biochemistry of the Eye. Springer Science & Business Media; 1991 Apr 30.