SubstratChanneling

SubstratChanneling (also known as substrate channeling) is a biochemical phenomenon in which reaction intermediates are transferred directly from one enzyme to the next with little or no diffusion into the surrounding solvent. This can occur when enzymes form transient or stable multi-enzyme complexes (metabolons) or when architectural features create a physical substrate channel between active sites. Channeling can also arise from tunnels or conduits within a single multidomain enzyme that pass a reactive intermediate from one active site to another, effectively shielding it from the bulk solvent.

By reducing diffusion distance and increasing local substrate concentration, substrate channeling can accelerate overall flux, synchronize sequential steps, and reduce loss or diversion of unstable or toxic intermediates. It also protects labile intermediates from hydrolysis or side reactions and can enable tight regulatory control of pathways. Evidence comes from kinetic experiments showing rates exceeding diffusion limits, as well as structural and biochemical data revealing enzyme assemblies, binding interfaces, and sometimes tunnels that connect active sites.

Classic examples include the tryptophan synthase complex, in which indole is transferred directly from the alpha to the beta subunit, and the pyruvate dehydrogenase complex, which channels pyruvate-derived intermediates through sequential catalytic sites within a single hub. SubstratChanneling is observed in diverse organisms and contexts and is a focus of studies in metabolism and synthetic biology, where engineered channeling aims to improve pathway efficiency.