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

Abstract

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 significantly 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.

The role of glycine in regulated cell death

“…Although glycine is considered a nonessential amino acid, its availability may, in fact, be limiting for all of its normal metabolic roles [201]. Manipulating glycine levels in vivo to potentially elicit protective effects is feasible because circulating glycine levels in multiple species, including humans and rodents, are at or below the EC50s (0.5–0.75) required for both its cytoprotective and anti-inflammatory effects.…”

Amino Acid Intakes Are Associated With Bone Mineral Density and Prevalence of Low Bone Mass in Women: Evidence From Discordant Monozygotic Twins

“…In particular, arginine, lysine, alanine, proline, leucine, and glutamine have been shown in vitro to stimulate insulin secretion, which promotes osteoblast growth and differentiation 15, 16. Arginine has also been shown to stimulate growth hormone secretion thereby promoting production of IGF‐1,17 whereas arginine, lysine, and glycine have been associated with an improvement in collagen formation or synthesis 18, 19. Leucine has a direct effect on the initiation of mRNA translation and is thought to be the most efficient of the branched‐chain amino acids at increasing muscle protein synthesis, which is critical for the maintenance of adequate bone strength and density 20…”

Amino Acid Biosynthesis

“…Threonine aldolase is an important source of glycine in S. cerevisiae [51]. Threonine forms a Schiff base with PLP which then catalyses a retro-aldol reaction to remove the side-chain as ethanal (see Box 1.3) [52,53].…”

“…53 Shikimate pathway.1.8 Biosynthesis of the Aromatic Amino Acids j49aromatic amino acids is an important mechanism for control of flux through the shikimate pathway. DAH7P synthase catalyses an aldol-like reaction in which the three-carbon unit PEP condenses with the four-carbon aldehyde, E4P.…”