JNTU B.Pharmacy II BIOCHEMISTRY Previous Question Paper (July - 2021 - R17)

Gluconeogenesis is the metabolic process of synthesizing glucose from non-carbohydrate precursors, primarily occurring in the liver and to a lesser extent in the kidneys. It is essential for maintaining blood glucose levels during fasting, starvation, or intense exercise.

Key steps include:

1. Conversion of Pyruvate to Phosphoenolpyruvate: Pyruvate is carboxylated to oxaloacetate by pyruvate carboxylase (requiring ATP and biotin), which is then converted to phosphoenolpyruvate by PEP carboxykinase.
2. Bypassing irreversible glycolytic steps: Fructose-1,6-bisphosphatase converts fructose-1,6-bisphosphate to fructose-6-phosphate, and glucose-6-phosphatase converts glucose-6-phosphate to free glucose.
3. Substrates: Major precursors include lactate (from anaerobic glycolysis), glycerol (from triglyceride breakdown), and glucogenic amino acids (primarily alanine).

Significance: It prevents hypoglycemia during periods of carbohydrate deprivation, provides glucose for tissues like the brain and erythrocytes that are strictly dependent on it, and helps clear metabolic waste products like lactate from the blood.

Blood glucose homeostasis is tightly regulated by a balance between glycogenesis, glycogenolysis, gluconeogenesis, and glycolysis, primarily controlled by the antagonistic actions of insulin and glucagon.

Key hormonal mechanisms:

1. Insulin: Secreted by pancreatic beta-cells in response to high blood glucose. It promotes glucose uptake in muscle and adipose tissue, stimulates glycogenesis and lipogenesis, and inhibits glycogenolysis and gluconeogenesis, thereby lowering blood glucose levels.
2. Glucagon: Secreted by pancreatic alpha-cells during low blood glucose. It stimulates glycogenolysis and gluconeogenesis in the liver, increasing glucose release into the bloodstream.
3. Epinephrine: Released during stress or exercise, it stimulates rapid glycogenolysis in skeletal muscle and liver to provide immediate energy.
4. Glucocorticoids (e.g., Cortisol): Promote gluconeogenesis by increasing the expression of key enzymes and mobilizing amino acids from muscle tissue to serve as precursors.

These hormones maintain blood glucose within the narrow physiological range of 70-110 mg/dL.