The effect of dietary modulation of sulfur amino acids on cystathionine β synthase-deficient mice

Warren D. Kruger, Sapna Gupta

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Cystathionine β synthase (CBS) is a key enzyme in the methionine and cysteine metabolic pathway, acting as a metabolic gatekeeper to regulate the flow of fixed sulfur from methionine to cysteine. Mutations in the CBS gene cause clinical CBS deficiency, a disease characterized by elevated plasma total homocysteine (tHcy) and methionine and decreased plasma cysteine. The treatment goal for CBS-deficient patients is to normalize the metabolic values of these three metabolites using a combination of vitamin therapy and dietary manipulation. To better understand the effectiveness of nutritional treatment strategies, we have performed a series of long-term dietary manipulation studies using our previously developed Tg-I278T Cbs-/- mouse model of CBS deficiency and sibling Tg-I278T Cbs+/- controls. Tg-I278T Cbs-/- mice have undetectable levels of CBS activity, extremely elevated plasma tHcy, modestly elevated plasma methionine, and low plasma cysteine. They exhibit several easily assayable phenotypes, including osteoporosis, loss of fat mass, reduced life span, and facial alopecia. The diets used in these studies differed in the amounts of sulfur amino acids or sulfur amino acid precursors. In this review, we will discuss our findings and their relevance to CBS deficiency and the concept of gene-diet interaction.

Original languageEnglish
Pages (from-to)80-90
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume1363
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Acetylcysteine/administration & dosage
  • Amino Acids, Sulfur/metabolism
  • Animals
  • Betaine/administration & dosage
  • Cystathionine beta-Synthase/deficiency
  • Diet
  • Dietary Supplements
  • Disease Models, Animal
  • Genotype
  • Homocystinuria/diet therapy
  • Humans
  • Metabolic Networks and Pathways
  • Methionine/administration & dosage
  • Mice
  • Mice, Knockout
  • Mutation
  • Phenotype

Fingerprint

Dive into the research topics of 'The effect of dietary modulation of sulfur amino acids on cystathionine β synthase-deficient mice'. Together they form a unique fingerprint.

Cite this