In vitro inhibition of 10-formyltetrahydrofolate dehydrogenase activity by acetaldehyde

Alcoholism has been associated with folate deficiency in humans and laboratory animals. Previous study showed that ethanol feeding reduces the dehydrogenase and hydrolase activity of 10-formyltetrahydrofolate dehydrogenase (FDH) in rat liver. Hepatic ethanol metabolism generates acetaldehyde and acetate. The mechanisms by which ethanol and its metabolites produce toxicity within the liver cells are unknown. We purified FDH from rat liver and investigated the effect of ethanol, acetaldehyde and acetate on the enzyme in vitro. Hepatic FDH activity was not reduced by ethanol or acetate directly. However, acetaldehyde was observed to reduce the dehydrogenase activity of FDH in a dose- and time-dependent manner with an apparent IC50 of 4 mM, while the hydrolase activity of FDH was not affected by acetaldehyde in vitro. These results suggest that the inhibition of hepatic FDH dehydrogenase activity induced by acetadehyde may play a role in ethanol toxicity.

Genomic DNA Methylation Status and Plasma Homocysteine in Choline- and Folate-Deficient Rats

Elevated plasma homocysteine ( Hcy) is a risk factor for cognitive dysfunction and Alzheimer disease, although the mechanism is still unknown. Both folate and betaine, a choline metabolite, play essential roles in the remethylation of Hcy to methionine. Choline deficiency may be associated with low folate status and high plasma Hcy. Alterations in DNA methylation also have established critical roles for methylation in development of the nervous system. This study was un-dertaken to assess the effect of choline and folate deficiency on Hcy metabolism and genomic DNA methylation status of the liver and brain. Groups of adult male Sprague Dawley rats were fed on a control, choline-deficient ( CD) , folate-deficient ( FD) or choline/folate-deficient ( CFD) diets for 8 weeks. FD resulted in a significantly lower hepatic folate ( 23%)(p < 0.001) and brain folate ( 69%)(p < 0.05) compared to the control group. However, plasma and brain folate remained unaltered by CD and hepatic folate reduced to 85% of the control by CD ( p < 0.05) . Plasma Hcy was signi-ficantly increased by FD ( 18.34 +/- 1.62 micrometer) and CFD ( 19.35 +/-3.62 micrometer) compared to the control ( 6.29 +/-0.60 micrometer) ( p < 0.001) , but remained unaltered by CD. FD depressed S-adenosylmethionine ( SAM) by 59% ( p < 0.001) and ele-vated S-adenosylhomocysteine ( SAH) by 47% in liver compared to the control group ( p < 0.001) . In contrast, brain SAM levels remained unaltered in CD, FD and CFD rats. Genomic DNA methylation status was reduced by FD in liver ( p< 0.05) . Genomic DNA hypomethylation was also observed in brain by CD, FD and CFD although it was not signifi-cantly different from the control group. Genomic DNA methylation status was correlated with folate stores in liver ( r = - 0.397, p < 0.05) and brain ( r = - 0.390, p < 0.05) , respectively. In conclusion, our data demonstrated that genomic DNA methylation and SAM level were reduced by folate deficiency in liver, but not in brain, and correlated with folate concentration in the tissue. The fact that folate deficiency had differential effects on SAM, SAH and genomic DNA methylation in liver and brain suggests that the Hcy metabolism and DNA methylation are regulated in tissue-specific ways.

Supplement Dose and Health-Related Life Style of Vitamin-Mineral Supplement User among Korean Middle-Aged / 대한지역사회영양학회지

We studied daily micronutrient intake from vitamin-mineral supplements, health-related life style, clinical case of diseases and food frequency of the Korean middle-aged (40 - 59 yr, n = 404) to compare the characteristics of non-user (n = 270) and user (n = 134) of vitamin-mineral supplements. Rate of supplement use of the middle-aged was 33.2% and there was significant difference in education level (p = 0.0084) and family income (p = 0.0476) of user and nonuser. Smoking habit (p = 0.0844) and drinking frequency (p = 0.0606) tended to be lower in a supplement user than a non-user. The medical history of a case was significantly higher in users (67.9%) than in non-users (44.4%) (p = 0.001), which suggests that medical history is one of the important motivations of supplement use. Supplement users had the medical history of digestive disease (34.1%), anemia (11.0%) and hypertension (9.9%) in order. Vitamin C was the most frequently supplemented nutrient (81.3%) among vitamin-mineral supplement, and the next orders were vitamins E (73.1%), B2 (68.7%) and B6 (60.4%). Mean intakes of vitamin B1, iron, selenium, vitamin E, and vitamin C from supplement was 4,260%, 4,030%, 1,660% and 1,330% of RDA, respectively. The supplement users tended to consume most food items including milk & milk products (p < 0.01), rice (p < 0.01), grains (p < 0.05) and cookies (p < 0.01) less frequently than non-users. Conclusively, nutrient intake of vitamin B1, iron, selenium, vitamin E, and vitamin C from supplement was excessively high compared to RDA. We suggest that the toxic effect of excessive supplementation should be informed to supplement user and nutritional education should be focused on the optimal supplement dose.