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A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism.

Publication ,  Journal Article
Nijhout, HF; Gregory, JF; Fitzpatrick, C; Cho, E; Lamers, KY; Ulrich, CM; Reed, MC
Published in: The Journal of nutrition
April 2009

We experimented with a mathematical model for 1-carbon metabolism and glutathione (GSH) synthesis to investigate the effects of vitamin B-6 deficiency on the reaction velocities and metabolite concentrations in this metabolic network. The mathematical model enabled us to independently alter the activities of each of the 5 vitamin B-6-dependent enzymes and thus determine which inhibitions were responsible for the experimentally observed consequences of a vitamin B-6 deficiency. The effect of vitamin B-6 deficiency on serine and glycine concentrations in tissues and plasma was almost entirely due to its effects on the activity of glycine decarboxylase. The effect of vitamin B-6 restriction on GSH concentrations appeared to be indirect, arising from the fact that vitamin B-6 restriction increases oxidative stress, which, in turn, affects several enzymes in 1-carbon metabolism as well as the GSH transporter. Vitamin B-6 restriction causes an abnormally high and prolonged homocysteine response to a methionine load test. This effect appeared to be mediated solely by its effects on cystathionine beta-synthase. Reduction of the enzymatic activity of serine hydroxymethyltransferase (SHMT) had negligible effects on most metabolite concentrations and reaction velocities. Reduction or total elimination of cytoplasmic SHMT had a surprisingly moderate effect on metabolite concentrations and reaction velocities. This corresponds to the experimental findings that a reduction in the enzymatic activity of SHMT has little effect on 1-carbon metabolism. Our simulations showed that the primary function of SHMT was to increase the rate by which the glycine-serine balance was reequilibrated after a perturbation.

Duke Scholars

Published In

The Journal of nutrition

DOI

EISSN

1541-6100

ISSN

0022-3166

Publication Date

April 2009

Volume

139

Issue

4

Start / End Page

784 / 791

Related Subject Headings

  • Vitamin B 6 Deficiency
  • Serine
  • Oxidative Stress
  • Nutrition & Dietetics
  • Models, Biological
  • Glycine Hydroxymethyltransferase
  • Glycine
  • Glutathione
  • Carbon
  • Biomarkers
 

Citation

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Nijhout, H. F., Gregory, J. F., Fitzpatrick, C., Cho, E., Lamers, K. Y., Ulrich, C. M., & Reed, M. C. (2009). A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism. The Journal of Nutrition, 139(4), 784–791. https://doi.org/10.3945/jn.109.104265
Nijhout, H Frederik, Jesse F. Gregory, Courtney Fitzpatrick, Eugenia Cho, K Yvonne Lamers, Cornelia M. Ulrich, and Michael C. Reed. “A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism.The Journal of Nutrition 139, no. 4 (April 2009): 784–91. https://doi.org/10.3945/jn.109.104265.
Nijhout HF, Gregory JF, Fitzpatrick C, Cho E, Lamers KY, Ulrich CM, et al. A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism. The Journal of nutrition. 2009 Apr;139(4):784–91.
Nijhout, H. Frederik, et al. “A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism.The Journal of Nutrition, vol. 139, no. 4, Apr. 2009, pp. 784–91. Epmc, doi:10.3945/jn.109.104265.
Nijhout HF, Gregory JF, Fitzpatrick C, Cho E, Lamers KY, Ulrich CM, Reed MC. A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism. The Journal of nutrition. 2009 Apr;139(4):784–791.
Journal cover image

Published In

The Journal of nutrition

DOI

EISSN

1541-6100

ISSN

0022-3166

Publication Date

April 2009

Volume

139

Issue

4

Start / End Page

784 / 791

Related Subject Headings

  • Vitamin B 6 Deficiency
  • Serine
  • Oxidative Stress
  • Nutrition & Dietetics
  • Models, Biological
  • Glycine Hydroxymethyltransferase
  • Glycine
  • Glutathione
  • Carbon
  • Biomarkers