A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis.

In a previous paper, we pointed out that the capability to synthesize glycine from serine is constrained by the stoichiometry of the glycine hydroxymethyltransferase reaction, which limits the amount of glycine produced to be no more than equimolar with the amount of C 1 units produced. This constraint predicts a shortage of available glycine if there are no adequate compensating processes. Here, we test this prediction by comparing all reported fl uxes for the production and consumption of glycine in a human adult. Detailed assessment of all possible sources of glycine shows that synthesis from serine accounts for more than 85% of the total, and that the amount of glycine available from synthesis, about 3 g/day, together with that available from the diet, in the range 1.5–3.0 g/day, may fall signifi cantly short of the amount needed for all metabolic uses, including collagen synthesis by about 10 g per day for a 70 kg human. This result supports earlier suggestions in the literature that glycine is a semi-essential amino acid and that it should be taken as a nutritional supplement to guarantee a healthy metabolism.

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 C1 unit: this produces an absolute dependence of the glycine production flux on the utilization of C1 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.