Nature’s NaBH4 is a nucleotide: NADH or NADPH
You met nucleotides, and their role in the structure of nucleic acids, earlier in this chapter. Nature also uses nucleotides as reagents. Here is the structure of AMP, just to remind you of a structure you met before, side by side with a pyridine-containing nucleotide.
These two nucleotides can combine together as a pyrophosphate to give a dinucleotide called nicotinamide adenine dinucleotide, or NAD (or NAD+—note the positively charged pyridinium). Notice that the link is not at all the same as in the nucleic acids. The latter are joined by one phosphate that links the 3′ and 5′ positions. Here we have a pyrophosphate link between the two 5′ positions.
The positively charged pyridinium ring is the part of the molecule which does all the work and from now on we will draw only the reactive part for clarity. NAD+ is one of nature’s most important oxidizing agents. Some biochemical pathway reactions use NADP instead, but this differs only in having an extra phosphate group on the adenosine portion so the same part structure will do for both. NAD+ and NADP both work by accepting a hydrogen atom and a pair of electrons from another compound. The reduced compounds are called NADH and NADPH.
The reduction of NAD+ (and NADP) is reversible, and NADH is itself a reducing agent. We will first look at one of its reactions: a typical reduction of a ketone. The ketone is pyruvic acid and the reduction product is lactic acid—both important metabolites. The reaction is cata lysed by an alcohol dehydrogenase.
This is a reaction that would also work in the laboratory with NaBH4 as the reducing agent, but there is a big difference. The product from the NaBH4 reaction must be racemic—the start ing material, reagent, and solvent are all achiral.
But the product from the enzymatic reaction is optically active. The two faces of pyruvic acid’s carbonyl group are enantiotopic and, by controlling the addition so that it occurs from one face only, the enzyme-catalysed reaction gives a single enantiomer of lactic acid.
