• Journal of Environmental Health Sciences
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• v.35 no.5
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• pp.343-354
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• 2009

Since Barker found associations between low birth weight and several chronic diseases later in life, the hypothesis of fetal origins of adult disease (aka, Barker Hypothesis) and epigenetics have been emerging as a new paradigm for geneenvironment interaction of chronic disease. Epigenetics is the study of heritable changes in gene silencing that occur without any change in DNA sequence. Gene expression can be regulated by several epigenetic mechanisms, including DNA methylation and histone modifications, which may be associated with chronic conditions, such as cancers, cardiovascular disease, and type-2 diabetes. One carbon metabolism which involves the transfer of a methyl group catalyzed by DNA methyltransferase is an important mechanism by which DNA methylation occurs in promoter regions and/or repetitive elements of the genome. Environmental factors may induce epigenetic modification through production of reactive oxygen species, alteration of methyltransferase activity, and/or interference with methyl donors. In this review, we introduce recent studies of epigenetic modification and environmental factors, such as heavy metals, environmental hormones, air pollution, diet and psychosocial stress. We also discuss epigenetic perspectives of early life environmental exposure and late life disease occurrence.

• Journal of Microbiology and Biotechnology
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• v.16 no.8
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• pp.1174-1179
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• 2006

The wild-type Corynebacterium glutamicum ATIC 13032 and Corynebacterium glutamicum ATTC 13032 lysC S301Y, exhibiting a deregulated aspartokinase, were compared concerning growth, lysine production, and intracellular carbon fluxes. Both strains differ by only one single nucleotide over the whole genome. In comparison to the wild-type, the mutant showed significant production of lysine with a molar yield of 0.087 mol (mol glucose$^{-1}$) whereas the biomass yield was reduced. The deregulation of aspartokinase further led to a global rearrangement of carbon flux throughout the whole central metabolism. This involved an increased flux through the pentose phosphate pathway (PPP) and an increased flux through anaplerosis. Because of this, the mutant revealed an enhanced supply of NADPH and oxaloacetate required for lysine biosynthesis. Additionally, the lumped flux through phosphoenolpyruvate carboxykinase and malic enzyme, withdrawing oxaloacetate back to the glycolysis and therefore detrimental for lysine production, was increased. The reason for this might be a contribution of malic enzyme to NADPH supply in the mutant in the mutant. The observed complex changes are remarkable, because they are due to the minimum genetic modification possible, the exchange of only one single nucleotide.

• Journal of Plant Biology
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• v.31 no.4
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• pp.277-288
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• 1988

The effects of ammonium ion and glutamate on CO2 fixation abilities and related carbon metabolism were investigated in pea (Pisum sativum L. cv. Sparkle) leaf discs under conditions favoring photorespiration (21% O2, 0.03% CO2) and nonphotorespiration (5% O2, 0.03% CO2). A concentration of more than 10 mM of NH4+ decreased the photosynthetic CO2 fixation and those inhibitory effects were more remarkable in 21% O2 than in 5% O2 conditions. The effect of glutamate on CO2 fixation was found to be independent of the O2 level, as glutamate increased the CO2 fixation under both 21% and 5% O2 conditions. L-methionine-dl-sulfoximine, an irreversible inhibitor of glutamate synthetase, however, inhibited the CO2 fixation markedly under 21% O2, but did not affect it under 5% O2 conditions. The treatment with NH4+ elevated the relative amounts of 14C incorporated into soluble components from 14CO2 with no relation to O2 levels, while glutamate increased 14C into insoluble components and neutral sugars. Glutamate, especially, seemed to stmulate the biosynthesis of starch under 5% O2 condition. These results indicated that NH4+ stimulated the degradation of sugar or starch and this proposal was confirmed by the increasing of pyruvate kinase activity in leaf discs treated with ammonium ion.

• YAKHAK HOEJI
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• v.37 no.5
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• pp.499-503
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• 1993

Betaine, a major component of Lycii Fructus, was evaluated for its anti-hepatotoxic activity on carbon tetrachloride-induced hepatotoxicity in primary cultured rat hepatocytes. Betaine was found to attenuate carbon tetrachloride-induced hepatotoxicity both morphologically and biochemically. Typical hepatocyte necrosis due to carbon tetrachloride seemed to be reduced by 50 to 500 $\mu{M}$ of betaine under microscopical observation. The value of glutamic pyruvic transaminase released from the hepatocytes into the medium significantly decreased as betaine concentration increased. Betaine also significantly elevated the reduced activities of some enzymes, cytochrome P-450, 7-ethoxycoumarin-0-deethylase and glutathione-S-transferase, involved in xenobiotic metabolism due to carbon tetrachloride-induced hepatotoxicity. These results demonstrate a possible hepato-protective role of betaine against fatty liver that could be easily induced by carbon tetrachloride.

• Journal of Microbiology and Biotechnology
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• v.18 no.12
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• pp.1958-1965
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• 2008

A denitrifying polyphosphate-accumulating bacterium (YKP-9) was isolated from activated sludge of a 5-stage biological nutrient removal process with step feed system. This organism was a Gram-negative, coccus-shaped, facultative aerobic chemoorganotroph. It had a respiratory type of metabolism with oxygen, nitrate, and nitrite as terminal electron acceptors. The 16S rRNA gene sequence of strain YKP-9 was most similar to the 16S rRNA gene sequence of Paracoccus sp. OL18 (AY312056) (similarity level, 97%). Denitrifying polyphosphate accumulation by strain YKP-9 was examined under anaerobic-anoxic and anaerobic-oxic batch conditions. It was able to use external carbon sources for polyhydroxyalkanoates(PHA) synthesis and to release phosphate under anaerobic condition. It accumulated polyphosphate and grew a little on energy provided by external carbon sources under anoxic condition, but did neither accumulate polyphosphate nor grow in the absence of external carbon sources under anoxic condition. Cells with intracellular PHA cannot accumulate polyphosphate in the absence of external carbon sources under anoxic condition. Under oxic condition, it grew but could not accumulate polyphosphate with external carbon sources. Based on the results from this study, strain YKP-9 is a new-type denitrifying polyphosphate-accumulating bacterium that accumulates polyphosphate only under anoxic condition, with nitrate and nitrite as the electron acceptors in the presence of external carbon sources.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.541-545
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• 2002

Pharmacokinetic characteristics of Acebutolol and its main metabolite, diacetolol, following a single 10 mg/kg oral dose, were investigated in rabbits with carbon tetrachloride-induced hepatic failure. Plasma concentrations of acebutolol and diacetolol were determined by a high performance liquid chromatography assay. The area under the plasma concentration-time curves (AUC) and maximum plasma concentration ($C_{max}$) of acebutolol were significantly increased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. The ratio of the diacetolol to total acebutolol in plasma (i.e., metabolite percentage rate) was significantly decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. Volume of distribution ($V_{d}$) and total body clearance ($CL_{t}$) of acebutolol were significantly decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. Slope of terminal phase ($\beta$) of acebutolol was significantly decreased in hepatic failure rabbits. These findings suggest that the $V_{d},{\;}CL_{t}$ and $\beta$ of acebutolol were significantly decreased as a result of inhibition of the hepatic metabolism in moderate to severe hepatic failure rabbits. Therefore, dose adjustment may be necessary for acebutolol in hypertensive patients with hepatic damage.

• YAKHAK HOEJI
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• v.33 no.3
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• pp.149-155
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• 1989

To predict the influence of carbon monoxide poisonining on cerebral energy metabolism, rats were exposed to 5000 ppm environment for 30 minutes. Carboxyhemoglobin (HBCO) saturation rate in this condition was 72% equally in male and female rats. Cerebral cortex in the rats showed lower level of ATP, glucose, creatine phosphate and higher level of lactate, pyruvate by anaerobic glycolysis. As for the levels of ATP, creatine phsphate and glucose, the cerebral cortex contents of them were larger in female rats of estrus than in male rats, whereas there was no difference between sexes in the levels of pyruvate and lactate. According to time passage from CO intoxication, the mode of changes in cerebral energy metabolite contents was similar in both sexes.

• Journal of Microbiology and Biotechnology
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• v.16 no.9
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• pp.1331-1337
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• 2006

A mathematical model has been proposed for the batch culture of Agaricus blazei with mixed carbon sources of glucose and dextrin. In the proposed model, the metabolism of A. blazei was divided into three parts: cell growth, exopolysaccharides (EPS) production, and another EPS production pathway activated by dextrin hydrolysis. Each pathway was described mathematically and incorporated into the mechanistic model structure. Batch cultures were carried out with six different carbon source compositions. Although parameters were estimated by using the experimental data from the two extreme cases such as glucose only and dextrin only, the model represented well the profiles of glucose, cell mass, and EPS concentrations for all the six different carbon source mixtures, showing a good interpolation capability. Of note, the lag in EPS production could be quite precisely predicted by assuming that the glucose-to-cell mass ratio was the governing factor for EPS production.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.973-977
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• 2002

The pharmacokinetic of paclitaxel (1 mg/kg, i.v.) was investigated in rabbits with carbon tetrachloride-induced hepatic failure. The area under the plasma concentration-time curve (AUC) of paclitaxel was significantly (p<0.01) increased in severe carbon tetrachloride-induced hepatic failure rabbits ($1364.54{\pm}382.07$ ng/ml$\cdot$hr) compared to that of normal rabbits ($567.52{\pm}141.88$ ng/ml$\cdot$hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($803.1{\pm}208.81$ ng/ml$\cdot$hr). The volume of distribution (Vd) (6.25$\pm$1.56 L) and the elimination rate constant($\beta$) ($0.09{\pm}0.025{\;}hr^{-1}$) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits were significantly (p<0.05) decreased compared to those of normal rabbits ($11.65<{\pm}2.91$L, $0.12{\pm}0.030{\;}hr^{-1}$), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($9.46{\pm}2.37$ L, $0.10{\pm}0.026{\;}hr^{-1}$). Total body clearance ($CL_t$) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits ($0.733{\pm}0.183$ L/hr/kg) was significantly (p<0.01) decreased compared to that of normal rabbits ($1.762{\pm}0.440$ L/hr/kg), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($1.245{\pm}0.311$ L/hr/kg). The half-life(t1/2) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits ($7.71{\pm}2.16$ hr) was significantly (p<0.05) increased compared to that of normal rabbits ($5.75{\pm}1.44$hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($6.77{\pm}1.76$hr). This results could be due to inhibition of paclitaxel metabolism in liver disorder rabbits since paclitaxel is essentially metabolized in liver. The findings suggest that the dosage regimen of paclitaxel should be adjusted when the drug would be administered in patients with liver disorder in a clinical situation.

• Nutritional Sciences
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• v.9 no.2
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• pp.106-111
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• 2006

Chronic alcohol consumption is associated with perturbation of hepatic metabolism of sulphur-containing amino acid. The goal of present study was to evaluate the influence of dietary supplementation of methionine or folate to chronically ethanol-fed mts on the metabolism of sulfur-containing amino acids and one-carbon metabolism. Sprague-Dawley male mts were fed Lieber-Decarli liquid diet with 0% ethanol (control), 36% ethanol (E), 36% ethanol combined with methionine supplement (EM) or folate supplement (EF) for 8 weeks. Hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), plasma folate and homocysteine (Hcy), urinary excretion of folate and formiminoglutamate were investigated after feeding experimental diets. Growth was retarded by 36% ethanol consupmtion (E, EM and EF) (p<0.01). Liver total fat (p<0.05) and plasma ALT (P<0.01) were increased by methionine supplementation (EM), implicating fatty liver and liver injury. Liver folate was increased slightly by folate supplementation (EF) (p=0.077). Urinary folate loss was increased 2.3 fold by ethanol consumption (E) and 17.2 fold by folate supplementation (EF), while decreased by methionine supplementation (EM) (p<0.000l). Plasma Hcy was increased 1.9 fold by methionine supplementation (EM) in ethanol-fed mts (p<0.05), which was related with decreased methionine synthase activity (p<0.05). Hepatic SAM/SAH ratio was depressed by methionine supplementation in ethanol-fed mts (EM) (p<0.05). Urinary formininoglutamate (Figlu) excretion after histidine loading was increased by ethanol ingestion and reduced by methionine supplementation (p<0.00l). Based on these data, methionine supplementation appears to accelerate histidine oxidation. In conclusion, dietary supplementation of methionine to ethanol-fed mts exacerbates alcoholic liver injury possibly by complicating sulphur-containing amino acid metabolism, as while it may have beneficial effects on folate and histidine metabolism.