BIOCHEMISTRY SEMINAR

TOPICS:Sorbitol PathwayBiochemical Basis of Diabetic Complications

SORBITOL PATHWAY(POLYOL PATHWAY)

There are 3 pathways of Glucose Metabolism: Glycolysis Pentose Phosphate Pathway Sorbitol Pathway Sorbitol Pathway is conversion of Glucose to Fructose via

Sorbitol.

AR SDH

NADPH NADP+ NAD+ NADH

SORBITOL PATHWAY IN THE HUMAN BODY

Sorbitol Pathway operates in the following organs:

LiverPancreasPlacentaBrainMale Accessory Sex Organs×Eye Lens×Kidneys×Nerve

Sorbitol Pathway operates under normal

conditions

Sorbitol Pathway causes abnormality in case of

Hyperglycemia

BIOCHEMICAL BASIS OF DIABETIC COMPLICATIONS

WHAT IS DIABETES?

DIABETIC COMPLICATONSDIABETIC COMPLICATONS

Accumulation of SorbitolSorbitol 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

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 H2O2). 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.