Branch-point stoichiometry can generate weak links in metabolism: the case of glycine biosynthesis

Although the metabolic network permits conversion between almost any pair of metabolites, this versatility fails at certain sites because of chemical constraints (kinetic, thermodynamic and stoichiometric) that seriously restrict particular conversions. We call these sites weak links in metabolism, as they can interfere harmfully with management of matter and energy if the network as a whole does not include adequate safeguards. A critical weak link is created in glycine biosynthesis by the stoichiometry of the reaction catalyzed by glycine hydroxymethyltransferase (EC 2.1.2.1), which converts serine into glycine plus one C, unit: this produces an absolute dependence of the glycine production flux on the utilization of C, units for other metabolic pathways that do not work coordinately with glycine use. It may not be possible, therefore, to ensure that glycine is always synthesized in sufficient quantities to meet optimal metabolic requirements.