1. BIOCHEMISTRY SEMINAR TOPICS: Sorbitol Pathway Biochemical Basis of Diabetic Complications

2. SORBITOL PATHWAY (POLYOL PATHWAY)

3. There are 3 pathways of Glucose Metabolism:  Glycolysis  Pentose Phosphate Pathway  Sorbitol Pathway Sorbitol Pathway is conversion of Glucose to Fructose via Sorbitol. GlucoseSorbitolFructose ARSDH NADPHNADP + NAD + NADH

4. SORBITOL PATHWAY IN THE HUMAN BODY Sorbitol Pathway operates in the following organs: Liver Pancreas Placenta Brain Male Accessory Sex Organs × Eye Lens × Kidneys × Nerve Sorbitol Pathway operates under normal conditions Sorbitol Pathway causes abnormality in case of Hyperglycemia

5. BIOCHEMICAL BASIS OF DIABETIC COMPLICATIONS

6. WHAT IS DIABETES? DIABETES D. MELLITUS TYPE ITYPE II

7. DIABETIC COMPLICATONS

9. Accumulation of Sorbitol Sorbitol being hydrophilic cannot pass the cell membrane. So it accumulates in the cell. Being highly osmotically active, Sorbitol attracts water inside the cell causing swelling up of cell. This has adverse effects on the following tissues: 1. Lens and retina- resulting in cataract 2. Kidneys- resulting in renal complications like nephritis and kidney failure. 3. Schwann cells of neurons- causing peripheral neuropathy

10. 1. OXIDATIVE STRESS When large amount of Sorbitol is formed, NADPH (required for its formation) gets depleted. As a result, it is not available for action of Glutathione Reductase (Reduces H 2 O 2 ). Hence free radicals are not removed from the body leading to damage to RBC membrane. 2. VASCULARIZATION NADPH is also required for Nitric Oxide Synthase activity for NO production. NO is an Endothelial Derived Relaxation Factor. Depletion of NADPH causes depletion of NO, so blood vessels remain constricted leading to Ischemia and Vascularization.