I came across a question (Q-5b) that asks:
Isocitrate Dehydrogenase in the [human] TCA cycle is associated with NAD+.
Why does it make good metabolic sense that it should use NADP+? Explain and show why this is so using appropriate structures and reactions.
This interesting paper argues the evolution of NADP-dependent IDH in prokaryotes as an adaptation to the need for growth in acetate. In the case of glucose growth, NADH can be obtained from the oxidative branch of the pentose phosphate pathway; in contrast, for acetate growth, PPP cannot run efficiently and IDH provides the predominant share of NADH. However, this ought to be a really irrelevant reason concerning IDH enzyme in humans since we do not have enzymes like isocitrate lyase etc. to entertain acetate growth!
Standard textbooks in biochemistry (Voet&Voet, Lehninger, et al) do not offer anything relevant except a generic note that NAD+ and NADP+ are respectively favored for oxidative and reductive metabolism. I am unsure about reasoning using this bit of trivia since TCA is an oxidative pathway! Fwiw, a question had been asked in Biology StackE about NADH vs NADPH where the accepted answer restates this.
To conclude, what is the metabolic advantage? Does there exist a way to arrive at the advantage using the fundamentals of biochemistry?