FIGURE 3.

Proposed catalytic cycle for serine palmitoyltransferase (SPT) with d₃-palmitoyl-CoA and L-serine-d₃ being the substrates. This scheme was modified from A. H. Merrill, Jr. (Merrill, 2011). An internal aldimine (Schiff base) formed between the cofactor pyridoxal 5’-phosphate (PLP) and an active site lysine residue (Enz-Lys-PLP, upper left) is replaced by the external aldimine through the incoming L-serine-d₃. Binding of d₃-palmitoyl-CoA results in transfer of serine α-deuterium to an enzymatic lysine residue (dashed box). The reaction proceeds as shown with free CoA, CO₂, and 3-ketosphinganine-d₅ (3KS-d₅) are released as products.