Dietary Betaine Promotes Generation of Hepatic S-Adenosylmethionine and Protects the Liver from Ethanol-Induced Fatty Infiltration

Previous studies have shown that ethanol feeding to rats alters methionine metabolism by decreasing the activity of methionine synthetase. This is the enzyme that converts homocysteine in the presence of vitamin B₁₂ and N⁵-methyltetrahydrofolate to methionine. The action of the ethanol results in an increase in the hepatic level of the substrate N⁵-methyltetrahydrofolate but as an adaptive mechanism, betaine homocysteine methyltransferase, is induced in order to maintain hepatic S-adenosylmethionine at normal levels. Continued ethanol feeding, beyond 2 months, however, produces depressed levels of hepatic S-adenosylmethionine. Because betaine homocysteine methyltransferase is induced in the livers of ethanolfed rats, this study was conducted to determine what effect the feeding of betaine, a substrate of betaine homocysteine methyltransferase, has on methionine metabolism in control and ethanol-fed animals. Control and ethanol-fed rats were given both betainelacking and betaine-containing liquid diets for 4 weeks, and parameters of methionine metabolism were measured. These measurements demonstrated that betaine administration doubled the hepatic levels of S-adenosylmethionine in control animals and increased by 4-fold the levels of hepatic S-adenosylmethionine in the ethanol-fed rats. The ethanol-induced infiltration of triglycerides in the liver was also reduced by the feeding of betaine to the ethanol-fed animals. These results indicate that betaine administration has the capacity to elevate hepatic S-adenosylmethionine and to prevent the ethanol-induced fatty liver.     

大鼠伏核内5-羟色胺样阳性终末与甲硫氨酸-脑啡肽样阳性神经元的突触联系

本研究用免疫组织化学双重染色技术,对伏核内５羟色胺（５ＨＴ）样免疫组织化学染色阳性终末与甲硫氨酸脑啡肽（ＭｅｔＥＮＫ）样阳性神经元之间的直接突触联系进行了观察。在光镜下观察到５ＨＴ样阳性纤维和终末位于伏核吻尾向全长的各部,尤以尾段的内侧部和腹侧部较密集,但未见５ＨＴ样阳性神经元;ＭｅｔＥＮＫ样阳性神经元的胞体、纤维和终末也主要分布于伏核的内侧部和腹侧部,但数量较少。在电镜下观察到５ＨＴ样阳性终末与ＭｅｔＥＮＫ样阳性神经元的胞体和树突形成以非对称性为主的轴体和轴树突触。以上结果为来自中脑的５ＨＴ能上行纤维与伏核内ＭｅｔＥＮＫ能神经元之间以串联联系方式发挥镇痛作用提供了形态学依据。     

Adipose tissue-liver axis in alcoholic liver disease

Alcoholic liver disease(ALD) remains an important health problem worldwide. The disease spectrum is featured by early steatosis, steatohepatitis(steatosis with inflammatory cells infiltration and necrosis), with some individuals ultimately progressing to fibrosis/cirrhosis. Although the disease progression is well characterized, no effective therapies are currently available for the treatment in humans. The mechanisms underlying the initiation and progression of ALD are multifactorial and complex. Emerging evidence supports that adipose tissue dysfunction contributes to the pathogenesis of ALD. In the first part of this review, we discuss the mechanisms whereby chronic alcohol exposure contributed to adipose tissue dysfunction, including cell death, inflammation and insulin resistance. It has been long known that aberrant hepatic methionine metabolism is a major metabolic abnormality induced by chronic alcohol exposure and plays an etiological role in the pathogenesis of ALD. The recent studies in our group documented the similar metabolic effect of chronic alcohol drinking on methionine in adipose tissue. In the second part of this review, we also briefly discuss the recent research progress in the field with a focus on how abnormal methionine metabolism in adipose tissue contributes to adipose tissue dysfunction and liver damage.     

The detection of cysteine-homocysteine mixed disulphide in plasma of normal fasting man.

Cysteine-homocysteine mixed disulphide, formed in the degradation of methionine, is detected routinely in the plasma of fasting patients homozygous for homocystinuria and in some obligate heteroxygotes. It has not hitherto been identified in the plasma of normal fasting man. Using a highly cross-linked resin with lithium citrate buffers on a JEOL. Amino Acid Analyser, we have detected the mixed disulphide in every one of the plasma samples from twenty normal fasting subjects. The mean concentration was 3.25 mumol/l (SD 0.85, N = 20), with a range of from 1.68 to 4.85 mumol/l. The other neutral and acidic amino acids were within the accepted normal range. The study shows that circulating homocysteine is normally not immediately transformed to cystathionine or remethylated to methionine; some combines with cysteine to form measurable amounts of mixed disulphide. Since homocysteine may produce endothelial damage, the present findings could be relevant to an understanding of the pathogenesis of vascular disease.     

Selection of two lines of mice based on latency to onset of methionine sulfoximine seizures

Purpose:  In various animals methionine sulfoximine (MSO) induces tonic–clonic seizures resembling the most striking form of human epilepsies. The aim of the present study was to select two lines of mice based upon differences in their latency to MSO-dependent seizures, in order to characterize them.
Methods:  Random crosses involving eight inbred mice strains were used to generate the starting population in which the first MSO challenge (75 mg/kg, i.p.) was performed. Two groups of 16 breeding pairs were established by mating mice having the shortest (MSO-Fast) and the longest (MSO-Slow) convulsion latencies. Mating and selection by latency to MSO (75 mg/kg, i.p.) was carried out over six generations.
Results:  MSO-Fast mice presented a significantly shorter MSO latency, and were more susceptible to MSO than MSO-Slow ones were. Electroencephalography (EEG) alterations were observed during the preconvulsive period when MSO-Fast mice were submitted to 75 mg/kg of MSO, and MSO-Slow ones to 200 mg/kg. Using another convulsant, kainic acid, the latency to convulse of MSO-Fast mice was significantly shorter than that of the MSO-Slow ones, whereas no difference was observed in response to pentylenetetrazole (PTZ). MSO-dependent convulsions were completely antagonized by MK-801, and partially by valproic acid, suggesting a preferential involvement of glutamatergic pathways.
Discussion:  The model that we have developed for MSO "sensitive" and "resistant" mice could allow for a better understanding of MSO mechanisms of epileptogenesis, and it may also constitute a useful approach for therapeutic actions of drugs.     

潍坊市汉族女性叶酸代谢关键酶基因多态性分布研究

目的:针对潍坊市汉族女性开展分子流行病学调查,研究叶酸代谢关键酶MTHFR和MTRR的基因多态性分布.方法:以孕期保健的670例汉族健康女性为研究对象,采集口腔黏膜上皮脱落细胞,抽提基因组DNA,使用荧光定量PCR方法检测MTH-FR C677T、A1298C和MTRR A66G基因多态性,进行统计分析.结果:1)入组...     

Urinary homocystine levels in a newborn infant with cystathionine synthase deficiency

A boy with homocystinuria due to cystathionine synthase deficiency was found to have hypermethioninaemia by neonatal blood screening, but was not diagnosed as homocystinuric until 3 months of age because urinary homocystine was not detected by the cyanidenitroprusside test or on two examinations with a sensitive amino acid autoanalyser. These findings indicate that tests for urinary homocystine should be made repeatedly with an amino acid auto-analyser in newborn infants with hypermethioninaemia until the enzyme defect is identified.     

蛋氨酸对大鼠胚胎发育影响的研究

研究蛋氨酸对孕９．５－１１．５ｄ大鼠胚胎发育的影响,方法：取孕９．５ｄ的大鼠胚胎,分别用蛋氨酸含量较低的纯牛血清和蛋氨酸＋牛血清为实验组,用大鼠血清做为对照组,在体外培养４８ｈ,并用Ｋｌｕｇ等人的评分系统对胚胎生长发育和形态进行评分,结果：在牛血清中培养的胚胎,其卵黄囊血循环、生长参数和蛋白质含量均低于牛血清＋蛋氨酸培养组,各器官发育异常率均高于牛血清＋蛋白氨酸培养组,加入蛋氨酸后,可以明显地改善     

Plasma homocysteine concentrations and the single nucleotide polymorphisms in the methionine synthase gene (MTR 2756A>G): Associations with the polycystic ovary syndrome An observational study

BACKGROUND: Elevated plasma homocysteine (Hcy) is a recognized risk factor for cardiovascular disease (CVD) and other defects. Biochemical and genetic studies have characterized molecular determinants contributing to alter Hcy metabolism. The vitamin B12 dependent enzyme methionine synthase (MTR) regulates de novo production of methionine from homocysteine. Defects in the activity of this enzyme may possibly predispose to higher plasma Hcy concentrations. STUDY DESIGN: We examined the associations between plasma Hcy concentrations and a single nucleotide polymorphism (SNP) in the MTR gene (MTR 2756A>G), and plasma folate concentrations, in 71 women (Caucasian and South Asian) attending a fertility clinic. We also determined the ethnic variations in the frequencies of the 3 genotypes of the MTR 2756 A>G gene. RESULTS: The frequency of the variant G allele was similar in the Caucasians and the South Asians (OR: 1.83; 95% CI: 0.79-4.23, p=0.2). The frequency was also similar in the PCOS and non-PCOS groups (OR: 0.88; 95% CI: 0.39-1.99). Plasma Hcy levels were significantly higher in women with PCOS compared with non-PCOS controls (p=0.05) and in Caucasian women with PCOS compared with Caucasian controls (p=0.04) in the presence of the MTR 2756 AA genotype (wild type). After adjusting for age, BMI, waist circumference and ethnicity, the significant predictors of plasma Hcy concentrations were plasma LDL, whole blood folate concentrations and a clinical diagnosis of PCOS. CONCLUSIONS: The important predictors of plasma Hcy concentration in women of reproductive age are whole blood folate concentrations, a background of PCOS and plasma LDL concentrations. The SNP 2756 A>G in the MTR gene does not appear to influence the plasma Hcy levels.     

The relationship between gene polymorphism of MTRR A66G and lower extremity deep venous thrombosis

ABSTRACT

Objective: To investigate the relationship between gene polymorphism of MTRR A66G and lower extremity deep venous thrombosis (DVT).

Methods: Two hundred and two patients with DVT as experimental group and 240 normal adults (control group) were enrolled in this study and white blood cells were collected, respectively. Polymorphism of the 66 loci in MTRR gene was detected by polymerase chain reaction-sequence-specific primers (PCR-SSP) in two groups. The frequency of genotype and allele distribution of each group was compared.

Results: The frequency of AA, AG and GG genotypes in 66 sites of MTRR gene were 26.76%, 4 3.66% and 29.58% in DVT group and 43.57%, 44.28% and 12.14% in control group, respectively. There was no significant difference in the distribution frequency between two groups (χ?=?3.2, P?>?.5).

Conclusions: The gene polymorphism of MTRR A66G may not be an independent genetic risk factor in DVT in China.