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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Nijhout, HF; Gregory, JF; Fitzpatrick, C; Cho, E; Lamers, KY; Ulrich, CM; Reed, MC

Published Date

  • April 2009

Published In

Volume / Issue

  • 139 / 4

Start / End Page

  • 784 - 791

PubMed ID

  • 19244383

Pubmed Central ID

  • 19244383

Electronic International Standard Serial Number (EISSN)

  • 1541-6100

International Standard Serial Number (ISSN)

  • 0022-3166

Digital Object Identifier (DOI)

  • 10.3945/jn.109.104265

Language

  • eng