Blog post: Jens: Why is there NADP in addition to NAD?

NAD+ and NADP+ are two coenzymes which are used by enzymes catalyzing the same kind of redox reactions. The reduced forms are NADH and NADPH. Both only differ in a phospho group far away from the active part of the molecule. So what is the advantage of having two different coenzymes?

Answer: Mainly reaction speed and partially also moving equilibrium of reversible reactions.

The physiological concentration ratio [NAD+] / [NADH] is in the range of 100 to 1000.

The physiological concentration ratio [NADP+] / [NADPH] is in the range of 0.1 to 0.001.

This means to speed up reactions the cell is using NAD+ in metabolic pathways that mainly serve to oxidize (typically catabolic pathways) and NADPH in metabolic pathways to reduce (typically anabolic pathways), since NAD+ has a much higher conectration than NADH and NADPH a higher one than NADP+.

Also the reducing power of both systems differ by a factor of 10000, which means by 28.5 kJ/mol.

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Details:

Note that the regeneration reactions of NADPH are both irreversible reactions (so that they work despite the unfavourable concentrations):

1) Glucose-6-phoshpate to 6-Phospho-Gluconate makes an acid out of an aldehyd. This is irreversible, because the acid has much less energy as an aldehyd (because it reacts further to an ion at physiological pH).

2) 6-Phospho-Gluconate to Ribulose-5-phosphate makes a shorter sugar out of a sugar acid. This is irreversible, because a CO2 is released.

The usual reactions of the NAD or NADP system are reactions which make C=O (keton) groups out of CHOH (alcohol) groups (or analogous reactions).

In addition as regeneration reaction there seem to be the possibility to reduce NADP+ to NADPH by oxidizing NADH to NAD+. This is done by a membrane enzyme in the inner mitochondiral membrane by using (reducing) the proton-gradient at this membrane.

Note also that there cannot be any enzymes which are catalyzing a reversible reaction and do not distinguish between NAD and NADP. Such an enzyme would just produce heat by removing the concentration gradient of both systems (and the same time slowing down metabolic pathways).Read and comment on the full post