• Proceedings of the PSK Conference
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• 2002.10a
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• pp.365.2-365.2
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• 2002

S-Adenosylhomocysteine hydrolase (SAH) catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and L -homocysteine and has been an attractive target for the development of broad spectrum antiviral agents. Neplanocin A and 9-(dihydroxycyclopent-4' -enyl)adenine (DHCeA) have been known to inhibit SAH by cofactor (NAD＋) depletion mechanism and their inhibition is reversed by the addition of NAD＋ or dialysis. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.186-190
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• 2002

S- Adenosylhomocysteine hydrolase $(SAH)^1$ catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and L-homocysteine. Inhibition of this enzyme accumulates S-adenosylhomocysteine, which in turn inhibits S-adenosyl-L-methionine dependent transmethylation, resulting in no formation of the capped methylated structure at the 5'-terminus of viral mRNA. Thus, S-adenosylhomocysteine hydrolase has been an attractive target for the development of broad spectrum of antiviral agents. (omitted)

• Journal of Nutrition and Health
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• v.36 no.8
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• pp.811-818
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• 2003

We investigated the effects of dietary folate supplementation on plasma homocysteine, vitamin B$_{12}$ and hepatic levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in diet-induced hyperhomocysteinemic rats. All animals were fed 0.3% homocysteine diet for 2 weeks, then they were placed either on a 0.3% homocystine or no homocystine with or without 8 mg/kg folate diet for 8 weeks. Homocystine diet induced hyperhomocysteinemia up to 3.5-fold at 10 weeks (28.0 $\pm$ 4.8 $\mu$mol/l vs. 7.9 $\pm$ 0.3 $\mu$mol/l). Dietary folate supplementation caused a significant decrease in plasma homocysteine levels which had been increased by a homocystine-diet. Also, dietary folate supplementation made them return to control levels at 4 wk when the diet was free of homocystine. Plasma folate levels were markedly decreased with homocystine diet with no folate supplementation. Plasma vitamin B$_{12}$ did not differ between groups. Dietary homocystine increased hepatic levels of SAM in folate supplementation group at 10 weeks (p<0.05). Dietary folate supplementation increased hepatic levels of SAM/SAH ratios in homocystine group (p<0.05). In conclusion, dietary folate supplementation can effectively ameliorate the detrimental effects of hyperhomocysteinemia.mia.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.245.3-246
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• 2003

S-Adenosylhomocysteine hydrolase (SAH) catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and L-homocysteine and has been an attractive target for the development of broad spectrum antiviral agents. Based on the potent inhibitory activity of neplanocin A against SAH, we have reported the synthesis and novel mechanism of action of fluoro-neplanocin A. (omitted)

• Journal of Microbiology and Biotechnology
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• v.16 no.6
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• pp.927-932
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• 2006

S-Adenosylmethionine (SAM) is a ubiquitous biomolecule serving mainly as a methyl donor. Our recent studies revealed that SAM controls antibiotic production in Streptomyces. In this study, the functional mode of SAM was studied in S. coelicolor and S. antibioticus ATCC11891, employing S-adenosylhomocysteine (SAH), a methylation reaction product of SAM. Actinorhodin biosynthesis did not require SAM as a methyl donor, whereas SAH enhanced the actinorhodin biosynthesis up to the level comparable to SAM, and the most effective concentration of SAH was higher than that of SAM. In the case of oleandomycin that requires SAM for its biosynthesis, both SAM and SAH at the concentration as low as 100 mM showed comparable efficacy in enhancing the production; SAM at 1 mM concentration additionally stimulated to give a 5-fold enhancement of oleandomycin production. In vitro autophosphorylation of protein kinase AfsK was found to be activated by both SAM and SAH, as well as other structurally related compounds. Our studies demonstrate that SAM regulates antibiotic biosynthesis in a mode independent of its role as a methyl donor and suggest that SAM acts directly as an intracellular signaling molecule for Streptomyces.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.163.1-163.1
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• 2003

The inhibitory activities of various analogues of adenosine (Group I, Group II, Group III, Group IV, Group V) were assayed by using recombinant human placental SAH hydrolase. The activity of the SAH hydrolase was determined by measuring the formation of AdoHcy from Ado and Hcy. AdoHcy was analyzed by HPLC using C18 reverse-phase column. The peak of AdoHcy was monitored at 258 nm. Among the tested compounds, fluoroneplanocin A (LJ-276) was the most potent inhibitor.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.790-792
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• 1998

• Journal of Embryo Transfer
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• v.30 no.3
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• pp.229-237
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• 2015

To improve the developmental potential of bovine somatic cell nuclear transfer (SCNT) embryos, this study compared the developmental rates to blastocyst stage in the SCNT embryos using donor fibroblasts treated with 5-azacytidine (5AC) and S-adenosylhomocysteine (SAH) at different concentrations. Their reprogramming efficiency level was investigated with level of telomerase activity. Donor fibroblasts isolated from adult ear skin of a cow were exposed to 5AC and SAH at different concentrations during 2 passages. After nuclear transfer into enucleated recipient oocytes, the cleavage and developmental rates were significantly (p<0.05) decreased in the SCNT embryos using 5AC-treated fibroblasts (5AC-SCNT embryos), compared with those of non-treated control (control-SCNT embryos) and SAH-treated fibroblasts (SAH-SCNT embryos). The developmental rates to blastocyst stage tended to be slightly increased in the SAH-SCNT embryos at each of the concentrations, and especially, the developmental rates in the SCNT embryos using 1.0 mM SAH-treated fibroblasts were significantly (p<0.05) higher than that of control SCNT embryos. The mean numbers of total and ICM cell in blastocysts were also significantly (p<0.05) decreased in the 5AC-SCNT embryos, compared with those of other SCNT blastocysts. Further, the level of telomerase activity was also significantly (p<0.05) decreased in the 5AC-SCNT embryos than those of control and SAH-SCNT embryos. Whereas, a significantly (p<0.05) up-regulated telomerase activity was observed in SAH-SCNT embryos, compare with that of control-SCNT embryos. In conclusion, SCNT embryos using hypomethylated donor cells with SAH, not 5AC, may improve the developmental potential and reprogramming efficiency.

• Nutrition Research and Practice
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• v.14 no.4
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• pp.309-321
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• 2020

BACKGROUND/OBJECTIVES: The present study aimed to evaluate the effects of folic acid supplementation in high-fructose-induced hepatic steatosis and clarify the underlying mechanism of folic acid supplementation. MATERIALS/METHODS: Male SD rats were fed control, 64% high-fructose diet, or 64% high-fructose diet with folic acid for eight weeks. Plasma glutamate-pyruvate transaminase, glutamate-oxaloacetate transaminase, lipid profiles, hepatic lipid content, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured. RESULTS: The HF diet significantly increased hepatic total lipid and triglyceride (TG) and decreased hepatic SAM, SAH, and SAM:SAH ratio. In rats fed a high fructose diet, folic acid supplementation significantly reduced hepatic TG, increased hepatic SAM, and alleviated hepatic steatosis. Moreover, folic acid supplementation in rats fed high fructose enhanced the levels of phosphorylated AMP-activated protein kinase (AMPK) and liver kinase B (LKB1) and inhibited phosphorylation of acetyl coenzyme A carboxylase (ACC) in the liver. CONCLUSIONS: These results suggest that the protective effect of folic acid supplementation in rats fed high fructose may include the activation of LKB1/AMPK/ACC and increased SAM in the liver, which inhibit hepatic lipogenesis, thus ameliorating hepatic steatosis. The present study may provide evidence for the beneficial effects of folic acid supplementation in the treatment of non-alcoholic fatty liver disease.

• Nutrition Research and Practice
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• v.9 no.2
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• pp.144-149
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• 2015

BACKGROUND/OBJECTIVE: The aim of this study was to examine the effect of high dietary methionine (Met) consumption on plasma and hepatic oxidative stress and dyslipidemia in chronic ethanol fed rats. MATERIALS/METHODS: Male Wistar rats were fed control or ethanol-containing liquid diets supplemented without (E group) or with DL-Met at 0.6% (EM1 group) or 0.8% (EM2 group) for five weeks. Plasma aminothiols, lipids, malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase were measured. Hepatic folate, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured. RESULTS: DL-Met supplementation was found to increase plasma levels of homocysteine (Hcy), triglyceride (TG), total cholesterol (TC), and MDA compared to rats fed ethanol alone and decrease plasma ALT. However, DL-Met supplementation did not significantly change plasma levels of HDL-cholesterol, cysteine, cysteinylglycine, and glutathione. In addition, DL-Met supplementation increased hepatic levels of folate, SAM, SAH, and SAM:SAH ratio. Our data showed that DL-Met supplementation can increase plasma oxidative stress and atherogenic effects by elevating plasma Hcy, TG, and TC in ethanol-fed rats. CONCLUSION: The present results demonstrate that Met supplementation increases plasma oxidative stress and atherogenic effects by inducing dyslipidemia and hyperhomocysteinemia in ethanol-fed rats.