Metal Ions Turn On A Stereoselective Nonenzymatic Reduction Of Keto Acids By The Coenzyme NADH

Coenzymes are thought to have played a central role in the emergence of metabolism. However, studies in the context of prebiotic chemistry face the problem that outside of enzymes, many such coenzymes do not react with their biological substrates.

Previous work suggests nicotinamide adenine dinucleotide (NAD) to be one of the most ancient coenzymes and to be central to early metabolism.

Yet, these models suffer from the logical gap that without enzymes, the reduced coenzyme NADH does not react with keto acids, some of its primary biological substrates.

We now report that aluminum or iron ions are catalysts for the reduction of keto acids by NADH. The ions mimic some of the roles of enzymes, such as the activation of substrates and the preorganization of keto acids with NADH. Moreover, the reaction proceeds with moderate stereoselectivity.

Our work gives insight into how an important coenzyme could have participated in a primitive metabolism that predated enzymes.

Graphical Abstract — Cell

Metal Ions Turn On A Stereoselective Nonenzymatic Reduction Of Keto Acids By The Coenzyme NADH, Cell (open access)

Astrobiology