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The effect of dietary modulation of sulfur amino acids on cystathionine beta synthase-deficient mice
Ann N Y Acad Sci. 2016 Jan;1363(1) :80-90
PMID: 26599618 PMCID: PMC4801721 URL: http://www.ncbi.nlm.nih.gov/pubmed/26599618
AbstractCystathionine beta 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.
NotesKruger, Warren D Gupta, Sapna eng P30 CA006927/CA/NCI NIH HHS/ R01 DK101404/DK/NIDDK NIH HHS/ R01 GM098772/GM/NIGMS NIH HHS/ 2015/11/26 06:00 Ann N Y Acad Sci. 2016 Jan;1363(1):80-90. doi: 10.1111/nyas.12967. Epub 2015 Nov 24.