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

Meléndez-Hevia, Enrique; Paz-Lugo, Patricia de

doi:10.1007/s12038-008-0097-5

Cited by 24 publications

(20 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…decrease in the need for the methyl group as a result of lower rate of creatine synthesis (Stead LM et al 2001). As discussed by Melendez-Hevia and colleagues (2008) and by Hofmeyr and Cornish-Bowden (2000), the stoichiometry of glycine biosynthesis from serine via glycine hydroxyl methyl transferase and its disposal via consumption of C1 units transferred via THF, results in unique metabolic constraints so that the rate glycine biosynthesis cannot exceed the flux of consumption of the methyl groups via THF or that they are closely linked. Based upon this analysis, we attribute the lower rate of glycine synthesis following creatine supplement to the decrease in the demand for glycine and for methyl groups for creatine synthesis.…”

Section: Discussionmentioning

confidence: 99%

Whole body creatine and protein kinetics in healthy men and women: effects of creatine and amino acid supplementation

et al. 2015

View full text Add to dashboard Cite

Creatine kinetics were measured in young healthy subjects, eight males and seven females, age 20–30 years, after an overnight fast on creatine free diet. Whole body turnover of glycine and its appearance in creatine was quantified using [1-13C] glycine and the rate of protein turnover was quantified using L-ring [2H5] phenylalanine. The creatine pool size was estimated by the dilution of a bolus [C2H3] creatine. Studies were repeated following a five days supplement creatine 21g.day−1 and following supplement amino acids 14.3 g.day−1. Creatine caused a ten folds increase in the plasma concentration of creatine and a 50% decrease in the concentration of guanidinoacetic acid. Plasma amino acids profile showed a significant decrease in glycine, glutamine and taurine and a significant increase in citrulline, valine, lysine and cysteine. There was a significant decrease in the rate of appearance of glycine, suggesting a decrease in de-novo synthesis (p=0.006). The fractional and absolute rate of synthesis of creatine was significantly decreased by supplemental creatine. Amino acid supplement had no impact on any of the parameters. Creatine supplement caused a significant decrease in the rate of synthesis of creatine. This is the first detailed analysis of creatine kinetics and the effects of creatine supplement in healthy young men and women. These methods can be applied for the analysis of creatine kinetics in different physiological states.

show abstract

Section: Discussionmentioning

confidence: 99%

Whole body creatine and protein kinetics in healthy men and women: effects of creatine and amino acid supplementation

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Glycine, which is 33% of collagen residues, has been typically classified as a ‘non-essential’ amino acid because human metabolism can synthesize it from serine. However, in previous work (Meléndez-Hevia and de Paz-Lugo 2008 ) we have shown that the glycine synthesis pathway has a strong stoichiometric restriction that limits its production, independently of the capacity and the regulatory mechanisms of the enzymes, as shown in Fig. 1 .…”

Section: Introductionmentioning

confidence: 90%

“…e Set of pathways that use glycine as metabolite for other biosynthesis processes. See Meléndez-Hevia and de Paz-Lugo ( 2008 ) …”

Section: Introductionmentioning

confidence: 99%

High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis

2018

Self Cite

View full text Add to dashboard Cite

Collagen synthesis is severely diminished in osteoarthritis; thus, enhancing it may help the regeneration of cartilage. This requires large amounts of glycine, proline and lysine. Previous works of our group have shown that glycine is an essential amino acid, which must be present in the diet in large amounts to satisfy the demands for collagen synthesis. Other authors have shown that proline is conditionally essential. In this work we studied the effect of these amino acids on type II collagen synthesis. Bovine articular chondrocytes were cultured under a wide range of different concentrations of glycine, proline and lysine. Chondrocytes were characterized by type II collagen immunocytochemistry of confluence monolayer cultures. Cell growth and viability were assayed by trypan blue dye exclusion method. Type II collagen was measured in the monolayer, every 48 h for 15 days by ELISA. Increase in concentrations of proline and lysine in the culture medium enhances the synthesis of type II collagen at low concentrations, but these effects decay before 1.0 mM. Increase of glycine as of 1.0 mM exceeds these effects and this increase continues more persistently by 60–75%. Since the large effects produced by proline and lysine are within the physiological range, while the effect of glycine corresponds to a much higher range, these results demonstrated a severe glycine deficiency for collagen synthesis. Thus, increasing glycine in the diet may well be a strategy for helping cartilage regeneration by enhancing collagen synthesis, which could contribute to the treatment and prevention of osteoarthritis.

show abstract

“…Glycine is a nonessential proteinogenic AA, primarily utilized in the synthesis of collagen, with limited function in the synthesis of other proteins and metabolic pathways [22]. Previous work by Meléndez-Hevia and de Paz-Lugo [23] suggests that a restriction in the stoichiometry of the glycine synthesis reaction may lead to insufficient glycine production relative to metabolic demand, making glycine an essential or conditionally essential AA. The CLV feeding system produced both ideal whey and acid whey with significantly higher concentrations of cysteine than the TMR system.…”

Section: Total Amino Acid Compositionmentioning

confidence: 99%

Impact of Bovine Diet on Metabolomic Profile of Skim Milk and Whey Protein Ingredients

et al. 2019

View full text Add to dashboard Cite

The influence of bovine diet on the metabolome of reconstituted skim milk powder (SMP) and protein ingredients produced from the milk of cows fed on pasture or concentrate-based diets was investigated. Cows were randomly assigned to diets consisting of perennial ryegrass only (GRS), perennial ryegrass/white clover sward (CLV), or indoor total mixed ration (TMR) for an entire lactation. Raw milk obtained from each group was processed at pilot scale, to produce SMP and sweet whey, and SMP was further processed at laboratory scale, to yield ideal whey and acid whey. The total amino acid composition and metabolome of each sample were analyzed, using high-performance cation exchange and a targeted combination of direct-injection mass spectrometry and reverse-phase liquid chromatography–tandem mass spectrometry (LC–MS/MS), respectively. The nitrogen composition of the products from each of the diets was similar, with one exception being the significantly higher nonprotein nitrogen content in TMR-derived skim milk powder than that from the GRS system. Total amino acid analysis showed significantly higher concentrations of glycine in GRS- and CLV-derived sweet whey and acid whey than in those from TMR. The cysteine contents of CLV-derived ideal whey and acid whey were significantly higher than for TMR, while the valine content of GRS-derived acid whey was significantly higher than TMR. The phenylalanine content of GRS-derived ideal whey was significantly higher than that from CLV. Metabolomic analysis showed significantly higher concentrations of the metabolites glutamine, valine, and phosphocreatine in each ingredient type derived from TMR than those from GRS or CLV, while the serine content of each GRS-derived ingredient type was significantly higher than that in TMR-derived ingredients. These results demonstrate that the type of bovine feeding system used can have a significant effect on the amino acid composition and metabolome of skim milk and whey powders and may aid in the selection of raw materials for product manufacture, while the clear separation between the samples gives further evidence for distinguishing milk products produced from different feeding systems based on LC–MS/MS.

show abstract

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

Cited by 24 publications

References 30 publications

Whole body creatine and protein kinetics in healthy men and women: effects of creatine and amino acid supplementation

Whole body creatine and protein kinetics in healthy men and women: effects of creatine and amino acid supplementation

High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis

Impact of Bovine Diet on Metabolomic Profile of Skim Milk and Whey Protein Ingredients

Contact Info

Product

Resources

About