Chapter 10, Problem 10.9PS

Lethal Synthesis. The leaves of Dichapetalum cymosum, a South African plant, are very poisonous. Animals that eat the leaves have convulsions and usually die shortly thereafter. One of the most pronounced effects of poisoning is a marked elevation in citrate concentration and a blockage of the citric acid cycle in many organs of the affected animal. The toxic agent in the leaves of the plant is fluoroacetate, but the actual poison in the tissues of the animal is fluorocitrate. If fluoroacetate is incubated with purified enzymes of the citric acid cycle, it has no inhibitory effect on enzyme activity.

(a) Why might you expect fluorocitrate to have an inhibitory effect on one or more of the citric acid cycle enzymes if incubated with the purified enzymes in vitro, even though fluoroacetate has no effect?

(b) Which enzyme in the citric acid cycle do you suspect is affected by fluorocitrate? Give two reasons for your answer.

(c) How could fluoroacetate be converted to fluorocitrate?

(d) Why is this phenomenon referred to as lethal synthesis?