In: Biology
Biochemistry Question
You have developed a new chemotherapeutic that acts to competitively inhibit a kinase you are targeting in cancer cells. In clinical trials, the drug is effective in killing the cancer cells, however patients also develop hemolytic anemia. After further testing you discover that the drug is also competitively inhibiting Phosphofructokinase-1 (PFK-1).
1. What effect would the drug have on the KM and Vmax of PFK-1?
2. Why would the inhibition of PFK-1 result in the development of hemolytic anemia? Explain.
1. Km of PFK1 will increase and Vmax will be constant. In competitive inhibition both the substrate and inhibitor has same molecular comparability so binding depends upon the concentration. So km increases as enzyme is recognising both the drug and pfk-1.Vmax will be constant as same vmax(without inhibitor) can be achieved by increasing the concentration of pfk-1 upto infinity.
2. Red blood cell(RBC) lacks nucleus and mitochondria. So ability to synthesize new protein or compensatory protein is negative. PFK-1 is a major enzyme of glycolysis which generates ATP. As ATP production stops all cellular activities will stop. Sodium potassium channel will not work as it requires ATP and potassium will leach out of cell membrane(it is more permeable than sodium ion). Intracellular fluid becomes hypotonic and cell shrinks.Death of RBC. Due to lack of ATP, rate of formation of rbc is less than rate of destruction resulting haemolytic anaemia.