Effect of Methionine Loading on 5-Methyltetrahydrofolate, S-Adenosylmethionine and S-Adenosylhomocysteine in Plasma of Healthy Humans

1996 ◽  
Vol 91 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Franziska M. T. Loehrer ◽  
Walter E. Haefeli ◽  
Christian P. Angst ◽  
Garry Browne ◽  
Greta Frick ◽  
...  

1. Elevated plasma homocysteine concentration, either in the fasting state or after methionine loading, is an independent risk factor for vascular disease in man. Methionine loading has been used to investigate impaired methionine metabolism, especially of the trans-sulphuration pathway, but most studies have focused on changes in homocysteine. 2. We investigated the effect of methionine excess on total plasma homocysteine, 5-methyltetrahydrofolate (which is the active form of folate in the remethylation of homocysteine to methionine), S-adenosylmethionine (the first metabolite of methionine) and S-adenosylhomocysteine (the demethylated product of S-adenosylmethionine) over 24 h in 12 healthy subjects. 3. As well as the expected increase in homocysteine (from 8.0 ± 1.3 to 32.6 ± 10.3 μmol/l, mean ± SD, P > 0.001), S-adenosylmethionine showed a significant transient increase (from 37.9 ± 25.0 to 240.3 ± 109.2 nmol/l, P > 0.001), which correlated well with homocysteine (r2 = 0.92, P > 0.001). 5-Methyltetrahydrofolate values decreased significantly (from 23.2 ± 7.2 to 13.1 ± 2.9 nmol/l, P > 0.01), and gradually returned to baseline levels after 24 h. No significant change over the time of measurement was found for S-adenosylhomocysteine. 4. The sequence of metabolic changes observed in this study strongly suggests that a change in either homocysteine or S-adenosylmethionine may cause a reduction in 5-methyltetrahydrofolate. This must be considered in evaluating the relationship between folate and homocysteine in vascular disease. The metabolic relationships illustrated in this study should be evaluated in the search for pathogenetic mechanisms of mild hyperhomocysteinaemia and vascular disease.

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Zhanjie Zheng ◽  
Jindong Wang ◽  
Lei Yi ◽  
Hui Yu ◽  
Lingli Kong ◽  
...  

The relationship between plasma homocysteine and behavioral and psychological symptoms of dementia (BPSD) has not been specifically investigated in previous research. In this study, we compared plasma homocysteine (Hcy) among 40 Alzheimer’s disease (AD) patients with BPSD, 37 AD patients without BPSD, and 39 healthy controls. Our results evidenced that the plasma homocysteine levels in AD patients with BPSD and without BPSD were higher than healthy controls and that the plasma homocysteine concentration in AD patients with BPSD was the highest among the three groups. Significant correlation between plasma homocysteine concentration and cognitive decline and duration of dementia was observed, but there was no correlation between BPSD and cognitive dysfunction or duration of dementia. In conclusion, this study showed for the first time that BPSD were associated with plasma homocysteine concentration in Alzheimer's dementia, and the results supported that hyperhomocysteine may take part in the pathogenesis of BPSD.


2007 ◽  
Vol 17 (1) ◽  
pp. 33-38
Author(s):  
K Zaw ◽  
M T Hasan ◽  
B Bhowmick ◽  
P B Khanna ◽  
E A Freeman

Interest in homocysteine's role in vascular disease was stimulated by the paper of McCully (1969) in which, based on autopsy evidence of extensive arterial thrombosis in two children with elevated plasma homocysteine concentrations and homocystinuria, he proposed that elevated plasma homocysteine (hyperhomocysteinaemia) can cause atherosclerotic vascular disease. A meta-analysis of subsequent prospective observational studies concluded that elevated homocysteine is indeed a modest independent predictor of ischaemic heart disease and stroke risk in healthy populations with a 25% reduction in serum homocysteine concentration, a reduction of approximately 3 micromol per litre (μmol/l) being associated with a 19% lower risk of stroke (odds ratio, 0.81; 95% confidence interval (CI), 0.69 – 0.95). In the nationally representative sample of US adults, elevated homocysteine concentration was independently associated with an increased likelihood of non-fatal stroke in both black and white adults. In this article, the current concepts relating homocysteine to ischaemic stroke are reviewed.


2000 ◽  
Vol 100 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Colm G. HANRATTY ◽  
Daniel F. MCAULEY ◽  
Lawrence T. MCGRATH ◽  
Ian S. YOUNG ◽  
G. Dennis JOHNSTON

A mild to moderate elevation of the total homocysteine concentration (tHcy) is now recognized as a risk factor for vascular disease. It is also associated with endothelial dysfunction in middle-aged and elderly individuals without overt atherosclerotic vascular disease. This is important, as endothelial dysfunction is a well recognized early and potentially reversible marker of the atherosclerotic process. We investigated whether mild hyperhomocysteinaemia was associated with endothelial dysfunction in otherwise healthy young males. We compared endothelial function, by measuring forearm blood flow, in 17 males with mild hyperhomocysteinaemia (defined as tHcy > 10 µmol/l) and 14 controls with low tHcy (defined as < 5 µmol/l). Forearm blood flow was measured in response to the intra-arterial infusion of acetylcholine (endothelial-dependent response) or sodium nitroprusside (endothelial-independent response). Responses to the vasoactive substances were expressed as the area under the curve of the change in forearm blood flow from baseline. Data are given as mean (95% confidence interval). The two groups were well matched for age, body mass index, pulse rate and blood pressure. tHcy was significantly different between the groups [12.3 (10.4–14.2) µmol/l compared with 4.9 (4.6–5.1) µmol/l; P < 0.001]. Concentrations of vitamin B12 and folate were significantly higher in the control group. There was no difference in basal forearm blood flow between the group with mild hyperhomocysteinaemia and the controls, and both the endothelial-dependent [37.5 (26.2–38.8) and 35.3 (26.1–44.4) arbitrary units respectively] and -independent [26.1 (22.2–29.9) and 25.9 (21.0–30.8) units respectively] responses were not significantly different between the groups. Thus the present study demonstrates that, in healthy adults, mild elevation of tHcy was not associated with impaired endothelial-dependent vasodilation. These data suggest an age effect with regard to homocysteine and endothelial dysfunction. The development of vascular disease in individuals with hyperhomocysteinaemia may only result with higher concentrations or after prolonged exposure.


1997 ◽  
Vol 8 (12) ◽  
pp. 1899-1905 ◽  
Author(s):  
A F Perna ◽  
D Ingrosso ◽  
N G De Santo ◽  
P Galletti ◽  
M Brunone ◽  
...  

Plasma homocysteine, a well-recognized risk factor for cardiovascular disease, is elevated in uremic patients on hemodialysis. The authors have recently demonstrated that one consequence is the reduction in red cell membrane protein methylation levels, caused by a rise of intracellular adenosylhomocysteine, a potent inhibitor of methyltransferases. Protein methylation is involved in a repair mechanism of damaged membrane proteins, and an impairment in methylation leads to the accumulation of altered proteins. Therapy with folates, cofactors in the transformation of homocysteine to methionine, is effective in lowering plasma homocysteine. This article details a study on the metabolic effects of oral methyltetrahydrofolate, the active form of folic acid, on 14 uremic hemodialysis patients. Two months of therapy led to a significant reduction of plasma homocysteine levels, with a proportional response to pre-folate levels. In five of 13 patients with homocysteine levels above 20 microM, plasma homocysteine level was reduced to less than 15 microM. After treatment, levels of adenosylmethionine, the methyl donor in transmethylations, had significantly increased; levels of adenosylhomocysteine had increased to a smaller extent. Therefore, the ratio between the two compounds, an excellent indicator of the presence and the degree of methylation inhibition, was significantly ameliorated. Methionine plasma levels increased after treatment in all patients and were correlated with posttreatment adenosylmethionine levels. It was concluded that treatment with methyltetrahydrofolate brings the plasma homocysteine concentration back to an "acceptable" level, and the metabolic consequences are in the direction of an increase in the normal flow of transmethylations, as monitored by an increase in the [adenosylmethionine]/[adenosylhomocysteine] ratio.


2000 ◽  
Vol 20 (4) ◽  
pp. 330-331 ◽  
Author(s):  
Peng Hai ◽  
Huang Qian ◽  
Li Yuefen ◽  
Sun Shenggang ◽  
Deng Xuejun ◽  
...  

2020 ◽  
Vol 19 (3) ◽  
pp. 243-249 ◽  
Author(s):  
Sevket Balta

: Vascular diseases are the main reason for morbidity and mortality worldwide. As we know, the earlier phase of vascular diseases is endothelial dysfunction in humans, the endothelial tissues play an important role in inflammation, coagulation, and angiogenesis, via organizing ligand-receptor associations and the various mediators’ secretion. We can use many inflammatory non-invasive tests (flowmediated dilatation, epicedial fat thickness, carotid-intima media thickness, arterial stiffness and anklebrachial index) for assessing the endothelial function. In addition, many biomarkers (ischemia modified albumin, pentraxin-3, E-selectin, angiopoietin, endothelial cell specific molecule 1, asymmetrical dimethylarginine, von Willebrand factor, endothelial microparticles and endothelial progenitor cells) can be used to evaluate endothelial dysfunction. We have focused on the relationship between endothelial dysfunction and inflammatory markers of vascular disease in this review.


Kidney ◽  
2008 ◽  
Vol 17 (3) ◽  
pp. 122-125 ◽  
Author(s):  
Simin Dashti-Khavidaki ◽  
Hossein Khalili ◽  
Elmira Barzegar ◽  
Mahboob Lessan-Pezeshki ◽  
Mohammad Reza Khoshayand ◽  
...  

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