Biochemistry You have been given a set of compounds to test their effect on iPFK
ID: 203623 • Letter: B
Question
Biochemistry
You have been given a set of compounds to test their effect on iPFK2 activity. Your preliminary screen found 4 lead compound hits, which you have further characterized at a concentration of 100 nM for each. Performing a full inhibitor analysis will take more resources. Which activity of iPFK2 would you want to inhibit or enhance to use as a chemotherapeutic? Why?
Based on what you know about the role of iPFK2 in the adenocarcinoma cells and the data in the table below, which compound(s) would you recommend to pursue as potential chemotherapeutics?
Kinase
Untreated
Compound 1
Compound 2
Compound 3
Compound 4
Vmax (mU/mg)
142
133
140
257
15
Fru-6-P Km (uM)
32
33
30
15
31
ATP Km (uM)
220
218
405
223
220
Bisphosphatase
Vmax (mU/mg)
0.2
240
0.2
0.3
0.6
Km (uM)
130
1.3
130
133
125
Kinase/bisphosphatase
710
0.6
700
857
25
Kinase
Untreated
Compound 1
Compound 2
Compound 3
Compound 4
Vmax (mU/mg)
142
133
140
257
15
Fru-6-P Km (uM)
32
33
30
15
31
ATP Km (uM)
220
218
405
223
220
Bisphosphatase
Vmax (mU/mg)
0.2
240
0.2
0.3
0.6
Km (uM)
130
1.3
130
133
125
Kinase/bisphosphatase
710
0.6
700
857
25
Explanation / Answer
iPKK2 enzyme is important to increase the glycolysis in the cancer cell. It untreated sample the kinase/bisphosphatase ratio is 710. It tells that kinase activity is more compare to biphosphatase activity.
Bisphosphatase is an enzyme involved to boost the gluconogenesis in the cell makes pyruvate to glucose molecule.
This is not good for cancer cells because glucose is the major source for the energy and specifically glycolysis.
Cancer shut down the TCA cycle due to shortage of O2 in the cells or hypoxia environment. The over all reason tells that in cancer cells kinase activity is high and bisphosphatase activity is low.
Compound 1 is the best for chemotherapeutic. We need to enhance the activity of bisphosphatase to control the glycolysis process. So cells not able to get enough energy to do their normal process and become dead.
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