Predict the effect of each of the following mutations on the

Predict the effect of each of the following mutations on the pace of glycolysis and gluconeogenesis in liver cells. Explain your reasoning. Loss of the allosteric site for ATP in phosphofructokinase fructose Loss of the phosphatase domain of the bifunctional enzyme that controls the level of fructose 2, 6-bisphosphate Increase in glucagon secretion A muscle biopsy from an individual who was incapable of carrying out prolonged, intense exercise contained a severe deficiency in the glycolytic enzyme phosphoglycerate mutase, which converts 3-phosphoglycerate to 2-phosphoglycerate. What is the explanation for the inability of this individual to exercise intensely? Does this individual suffer from lactic acid buildup in the muscle? Explain. Glucose labeled with at 14^C at C-6 is added to a solution containing the enzymes and cofactors of oxidative phase of the pentose phosphate pathway. What is the fate of the radioactive label? If you wanted the radioactive label to end up in Sedoheptulose 7-phosphate, what enzymes would you need to add to the solution mentioned above?

Solution

Phosphofructikinase 1 regulates the first step in glycolysis i.e. conversion of fructose-6-phosphate to fructose 1,6-bisphosphate by using one ATP molecule. If allosteric substrate binding site for ATP is lost, the ATP cannot bind to the protein and bring about this conversion.

ATP also binds to the enzye as an inhibitor of the enzyme by binding to the allosteric inhibitory site to bring about forrmation of T state of enzyme which is inactive. At low levels of ATP/AMP concentration the enzyme is activated to bring about glycolysis and at high levels the same is converted to R state.

Phosphofructokinase1 has both sites for ATP as a substrate and as an inhibitor. if any one of the sites are impaired the glycolysis cycle will be deregulated.

2) phosphatse domain is located in the -termminal of Phosphofructokinase 2 enzyme which brings about conversion of f-6-P to F-2,6-bisphosphate

insulin activates PFK2 through protein phosphatase in bringing about change in energy state of the protein and favouring glycolysis. if the phosphatase domain is lost, the glycolysis cycle will be hampered causing high glucose levels in blood.

3) increase in glucagon secretion indicates low glucose concentration. this is a feedback mechanism by the cells to restore energy under low glucose concentrations. Glycogen activates gluconeogenesis and glycogenolysis. when glucagon stores deplete gluconeogenesis is activated and glycolysis is shut causing intermediates of glycolysis to shift to gluconeogenesis