Mechanisms and Effects of Substrate Channelling in Enzymatic Cascades

Substrate or metabolite channelling is a transfer of intermediates produced by one enzyme to the sequential enzyme of a reaction cascade or metabolic pathway, without releasing them entirely into bulk. Despite an enormous effort and more than three decades of research, substrate channelling remains the subject of continuing debates and active investigation. Herein, we review the benefits and mechanisms of substrate channelling in vivo and in vitro. We discuss critically the effects that substrate channelling can have on enzymatic cascades, including speeding up or slowing down reaction cascades and protecting intermediates from sequestration and enzymes' surroundings from toxic or otherwise detrimental intermediates. We also discuss how macromolecular crowding affects substrate channelling and point out the galore of open questions.