Date of Award
Master of Science
Food Science and Human Nutrition
Kevin L. Schalinske
Homeostasic balance of one-carbon metabolism is highly dependent upon derivatives of folate and is vital for the prevention of multiple disease states, including vascular disease, birth defects, neurological disorders, and cancer. Homocysteine, a non-protein forming amino acid, accumulates in the absence of 5-methyltetrahydrofolate and represents both a marker for reduced cellular methylation potential and elicitor of pathogenesis (Cattaneo, 1999). In addition to cofactors like folate, vitamin B6, B12, and B2, various bioactive compounds are believed to influence the same cellular processes either directly or indirectly (Strain et al., 2004). The isoflavone genistein exhibits estrogen-like properties and has been implicated in the prevention of various diseases, including those involving hyperhomocysteinemia (Marini et al., 2009). Genistein has been shown to stably alter DNA methyltransferase and histone acetyltransferase activities independently of folate (Dolinoy et al, 2006; Li et al., 2009). This study was conducted to determine if genistein could modulate one-carbon metabolism during diet-induced folate deficiency. Specifically, we aimed to determine whether genistein is able to prevent hyperhomocysteinemia caused by moderate folate deficiency and classify any changes in relevant enzyme function, including those related to transmethylation, remethylation, and transsulfuration pathways, as well as alterations in genomic DNA methylation patterns. Administration of genistein (300 mg/kg diet) reduced plasma homocysteine concentrations in rats fed a folate-deficient diet in three independent studies without consistent alterations in enzyme activity or expression. Attenuation of plasma homocysteine was similar and occurred independently across each study at 10, 24, and 59 d of supplementation. There were no differences in genomic DNA methylation patterns or measured hepatic transmethylation, remethylation, and transsulfuration enzymes as determined by analysis of enzyme expression and activity. Future research is warranted to determine the specific actions of genistein related to its ability to mediate one-carbon metabolism during moderate folate deficiency.
Nonnecke, Eric, "Genistein mediates perturbations in one-carbon metabolism during diet-induced folate deficiency" (2010). Graduate Theses and Dissertations. 11598.