Question

1. Hexokinase II (the isoform usually discussed in biochemistry classes as part of glycolysis) catalyzes the first step in glycolysis. The isoform of hexokinase that is expressed in most tumor cells is bound to the mitochondrial outer membrane facing the cytosol. Propose two reasons why this would be beneficial to the tumor cell.

2. Another highly regulated enzyme in glycolysis is phosphofructokinase (PFK1). There is evidence from some tumors that PFK1 undergoes a posttranslational proteolysis that yields a truncated functional enzyme (47 kD vs 85 kD) that is insensitive to citrate and ATP. How might this work and why would it be beneficial for a tumor cell?

Answer 1

1) A Key role of hexokinase-II in cancer cells surviva by suppressing cell death. ina given highly glycolytic tumor ,a predominant fraction of the HK II is localized on the mitochondria with the enzyme anchored to the VDA protein via an N- terminal - binding domain.

2) PFK1 a key regulatory enzyme of glycolysis that is ormally under the control of feedback inhibition , undergoes posttranslational modifications. after proteolytic clevage of the c- terinal portion of theenzyme , an acive , shorter 47-kDa fragmet was formed that was insensitive to citrate and ATP inhibition.

the fructose -6- bisphosphate cycle catalyzed by 6- phosphofructo-1-kinase iso enzymes , plays a role in controlling glycolytic rattes. PFK1/ FBpase1 activities areallosterically regulated by fructose -2,6- bisphosphate, the product of the enzymatic activity of the dual kinase . trageting these isomers , either directly or by inhibiting their activating factors, could be a approach for treating cancers.