MT L1 Antimetabolites - Sugar-modified nucleosides

Question 1

name three sugar-modified neucleotides

Answer 1

cytarabine
fludarabine
gemcitabine

Question 2

why is gemcitabine 100x more potent? (2)

Answer 2

Self potentiates in two ways:

1. F2dCDP is an inhibitor of 2 enzymes that produce dCTP
2. dCTP depletion activates dCK increasing first step of activation

Question 3

what are the 2 enzymes that prodice dCTP

Answer 3

CTP synthase

riboneucleotide reductase

Question 4

action of cytarabine (2)

Answer 4

triphosphate inhibits DNA polymerase by mimicing dCTP

also
some incorporation into DNA which becomes non-funcitonal and falls appart due to extra OH group

Question 5

action of fludarabine

Answer 5

triphosphate inhibits DNA polymerase as it’s an analogue of dATP

Question 6

action of gemcitabine

Answer 6

triphosphate inbiits DNA polymerase as analogue of dCTP