JNTU B.Pharmacy II BIOCHEMISTRY Previous Question Paper (November/December - 2020 - R17)

Glycolysis, also known as the Embden-Meyerhof-Parnas pathway, is the metabolic process that converts one molecule of glucose into two molecules of pyruvate, generating ATP and NADH in the process. It occurs in the cytosol of the cell and consists of ten enzyme-catalyzed steps divided into the preparatory phase and the pay-off phase.

The pathway proceeds as follows:

1. Glucose is phosphorylated to Glucose-6-phosphate by hexokinase (consuming 1 ATP).
2. Glucose-6-phosphate is isomerized to Fructose-6-phosphate by phosphoglucose isomerase.
3. Fructose-6-phosphate is phosphorylated to Fructose-1,6-bisphosphate by phosphofructokinase-1 (consuming 1 ATP).
4. Fructose-1,6-bisphosphate is cleaved into Glyceraldehyde-3-phosphate (G3P) and Dihydroxyacetone phosphate (DHAP) by aldolase.
5. DHAP is converted to a second molecule of G3P by triose phosphate isomerase.
6. G3P is oxidized and phosphorylated to 1,3-Bisphosphoglycerate by G3P dehydrogenase (producing 2 NADH).
7. 1,3-Bisphosphoglycerate is converted to 3-Phosphoglycerate by phosphoglycerate kinase (producing 2 ATP).
8. 3-Phosphoglycerate is converted to 2-Phosphoglycerate by phosphoglycerate mutase.
9. 2-Phosphoglycerate is dehydrated to Phosphoenolpyruvate (PEP) by enolase.
10. PEP is converted to Pyruvate by pyruvate kinase (producing 2 ATP).

Energetics of Glycolysis:

The net energy yield per glucose molecule is 2 ATP and 2 NADH. In the preparatory phase, 2 ATP are consumed. In the pay-off phase, 4 ATP are produced via substrate-level phosphorylation, resulting in a net gain of 2 ATP. Additionally, the 2 NADH produced can yield further ATP via the electron transport chain under aerobic conditions.

The Hexose Monophosphate (HMP) shunt, also known as the Pentose Phosphate Pathway, is an alternative metabolic route for glucose oxidation that occurs in the cytosol. Unlike glycolysis, it does not generate ATP but produces essential precursors for biosynthesis and reducing power.

The pathway consists of two distinct phases:

1. Oxidative Phase (Irreversible): Glucose-6-phosphate is converted to 6-phosphogluconate by glucose-6-phosphate dehydrogenase (G6PD), reducing NADP+ to NADPH. This is followed by oxidative decarboxylation to produce ribulose-5-phosphate and a second molecule of NADPH.
2. Non-Oxidative Phase (Reversible): This phase involves a series of sugar-phosphate interconversions catalyzed by transketolase and transaldolase enzymes. It converts ribulose-5-phosphate into ribose-5-phosphate (for nucleotide synthesis) or recycles pentose phosphates back into glycolytic intermediates like fructose-6-phosphate and glyceraldehyde-3-phosphate.

The significance of the HMP shunt includes:

• Production of NADPH: NADPH is vital for reductive biosynthesis of fatty acids and cholesterol, and for maintaining the reduced state of glutathione, which protects erythrocytes from oxidative damage.
• Synthesis of Ribose-5-Phosphate: It provides the essential pentose sugars required for the synthesis of nucleotides, DNA, RNA, and coenzymes like ATP, NADH, and FAD.
• Metabolism of Pentoses: It allows dietary pentoses to enter the glycolytic pathway.
• Erythrocyte Integrity: In red blood cells, the HMP shunt is the sole source of NADPH, making the pathway critical for preventing hemolysis caused by oxidative stress.