JNTU B.Pharmacy II BIOCHEMISTRY Previous Question Paper (March - 2022 - 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 or intense exercise.

The pathway bypasses the three irreversible steps of glycolysis using unique enzymes:

1. Pyruvate to Phosphoenolpyruvate (PEP): Pyruvate is converted to oxaloacetate by pyruvate carboxylase (requiring biotin and ATP). Oxaloacetate is then converted to PEP by PEP carboxykinase (requiring GTP).
2. Fructose-1,6-bisphosphate to Fructose-6-phosphate: This bypasses the phosphofructokinase-1 reaction, catalyzed by fructose-1,6-bisphosphatase, which removes a phosphate group.
3. Glucose-6-phosphate to Glucose: The final step, catalyzed by glucose-6-phosphatase (found in the endoplasmic reticulum), removes the phosphate to release free glucose into the blood.

The overall reaction requires 6 ATP/GTP molecules per glucose synthesized, making it an energy-expensive process regulated by hormones like glucagon and cortisol, which promote the expression of these key enzymes.

Inhibitors of the Electron Transport Chain (ETC) block specific complexes, preventing electron flow and ATP synthesis, which leads to cellular toxicity. Key inhibitors include:

• Complex I Inhibitors: Rotenone (a pesticide) and Amytal (a barbiturate) block electron transfer from NADH to Coenzyme Q.
• Complex III Inhibitors: Antimycin A inhibits the oxidation of ubiquinol, effectively stopping the flow of electrons to cytochrome c.
• Complex IV Inhibitors: Cyanide, Carbon Monoxide, and Azide bind to the ferric (Fe3+) iron in cytochrome a3. This prevents the final transfer of electrons to oxygen, halting the entire chain and causing chemical asphyxiation.
• ATP Synthase Inhibitor: Oligomycin binds to the F0 subunit of ATP synthase, blocking the proton channel and preventing the phosphorylation of ADP to ATP, which indirectly inhibits the ETC by creating a proton gradient buildup.