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a) In the muscle, although hexokinase is the first irreversible step in glycolys

ID: 63065 • Letter: A

Question

a) In the muscle, although hexokinase is the first irreversible step in glycolysis, phosphofructokinase (PFK-1) is the primary point of regulation and the first committed step. Please explain why the reaction catalyzed by hexokinase is notthe first committed step of glycolysis in muscle? Please explain why the reaction catalyzed by PFK-1 is the first committed step of glycolysis in the muscle.

b) Unlike muscle, in the brain, hexokinase is the first committed step of glycolysis. Please explain why this is. Assume the brain has negligible glycogen stores and pentose phosphate pathway activity

a) In the muscle, although hexokinase is the first irreversible step in glycolysis, phosphofructokinase (PFK - 1) is the primary point of regulation and the first committed step. Please explain why the reaction catalyzed by hexokinase is notthe first committed step of glycolysis in muscle? Please explain why the reaction catalyzed by PFK - 1 is the first committed step of glycolysis in the muscle. b) Unlike muscle, in the brain, hexokinase is the first committed step of glycolysis. Please explain why this is. Assume the brain has negligible glycogen stores and pentose phosphate pathway activity

Explanation / Answer

a. Immediately after glucose enters into the cells, it is phosphorylated to Glucose - 6- phosphate. Phosphorylation is essential to prevent leakage of glucose from cells. Negatively charged g-6-p cannot tranverse the cell membrane. Muscle cells can store excess glucose in glycogen. Glucose-6-phosphate is converted to glu-1-p, and is incorporated into glycogen. Since excess G-6-P is converted into glycogen, the hexokinase is not under the regulation of g-6-p.

Muscles can store glucose in the form of glycogen. Most of the times, muscles obtain glucose by hydrolysis of glycogen, which yields glucose-i-phosphate, but not glucose. G-1-P is isomerised to glucose-6-phosphate by a mutase enzyme. This G-6-P enters glycolysis but not glucose. Hence, hexokinase regulation is not required for muscle cells.

b. Contrary to this, brain cells cannot store glucose in the form of glycogen. Hence, G6P provides a feedback regulation to prevent accumulation of excess glucose in the brain cell, until the glucose in the cells is used up through glycolysis.