Fig. 10

Proposed mechanism of glycine-promoted complement-dependent killing. First, exogenous glycine passes into the cytoplasm, where it is converted to serine and threonine by GlyA and Kbl, respectively; second, serine fluxes to the TCA cycle and promotes α-Ketoglutarate generation, which inhibits ATP synthase, while elevated glycine, serine and threonine catabolic pathway does not favor fluxing purine metabolism due to stronger substrate activation to GlyA, thereby decreasing AMP and ADP biosynthesis. These lead to ATP reduction and the decrease of ATP affects cAMP and cAMP-CRP complex; third, glycine in conjunction with serum elevates expression and membrane deposition of HtrE, NfrA, and YhcD by FlhC and CsgD in a manner of cAMP-CRP complex; and fourth, these outer membrane proteins promote binding of complement, formation of MAC and subsequent cell death. On the catabolic side, glycine enters the TCA cycle and stimulates synthesis of NADH and increases membrane potential, which facilitates the binding of complement to the outer membrane. It is clear that metabolites dominate the novel demonstrated metabolic regulation pathways. Colors: pink, upregulation; grass green, down-regulation