Homocysteine Imbalance: a Pathological Metabolic Marker

Schalinske, Kevin L.; Smazal, Anne L.

doi:10.3945/an.112.002758

Cited by 140 publications

(121 citation statements)

References 98 publications

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“…Trans-sulfuration is favored with the upregulation of CBS. Several studies have reported that increased trans-sulfuration resulted in higher levels of cysteine, which can serve as a substrate for gluconeogenesis via its conversion to pyruvate, leading to hyperglycemia (14,29,37). However, we observed that random glucose levels were lower in the DJB group than in the control group.…”

Section: Discussioncontrasting

confidence: 54%

Changes in one-carbon metabolism after duodenal-jejunal bypass surgery

Jung

Lee

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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GS. Changes in one-carbon metabolism after duodenal-jejunal bypass surgery. Am J Physiol Endocrinol Metab 310: E624 -E632, 2016. First published January 19, 2016 doi:10.1152/ajpendo.00260.2015.-Bariatric surgery alleviates obesity and ameliorates glucose tolerance. Using metabolomic and proteomic profiles, we evaluated metabolic changes in serum and liver tissue after duodenal-jejunal bypass (DJB) surgery in rats fed a normal chow diet. We found that the levels of vitamin B 12 in the sera of DJB rates were decreased. In the liver of DJB rats, betaine-homocysteine S-methyltransferase levels were decreased, whereas serine, cystathionine, cysteine, glutathione, cystathionine ␤-synthase, glutathione S-transferase, and aldehyde dehydrogenase levels were increased. These results suggested that DJB surgery enhanced trans-sulfuration and its consecutive reactions such as detoxification and the scavenging activities of reactive oxygen species. In addition, DJB rats showed higher levels of purine metabolites such as ATP, ADP, AMP, and inosine monophosphate. Decreased guanine deaminase, as well as lower levels of hypoxanthine, indicated that DJB surgery limited the purine degradation process. In particular, the AMP/ATP ratio and phosphorylation of AMP-activated protein kinase increased after DJB surgery, which led to enhanced energy production and increased catabolic pathway activity, such as fatty acid oxidation and glucose transport. This study shows that bariatric surgery altered transsulfuration and purine metabolism in the liver. Characterization of these mechanisms increases our understanding of the benefits of bariatric surgery. gastric bypass surgery; metabolomics; proteomics; metabolism DIABETES AFFECTS ALMOST 10% of the general population and is a leading cause of disability, morbidity, and mortality (15). Although glycemic control and risk factor management have improved, the prevalence of diabetes is still increasing (8, 9). Furthermore, current drug-based therapies for diabetes rarely lead to remission. Thus, there is an urgent need for new therapeutic options.Bariatric surgery provides a reliable treatment that results in substantial and sustained weight loss in morbidly obese patients and provides a substantial improvement in cases of type 2 diabetes mellitus (T2DM) (5, 6). Bariatric surgery is significantly better than intensive medical therapy for the glycemic control of T2DM at 1-2 years (10,13,24,38). However, the mechanism by which bariatric surgery results in the remission of T2DM remains unclear. Moreover, given that the initial body mass index and postoperative weight loss values are poor predictors of the efficacy of bariatric surgery in patients with diabetes and metabolic syndrome (27, 41), the improvement in glycemia after bariatric surgery is not simply a consequence of sustained weight loss. Therefore, understanding the underlying mechanism of bariatric surgery with respect to the resolution of T2DM is important for the development of more effective and less invasive T2DM therapeutic strategie...

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Section: Discussioncontrasting

confidence: 54%

Changes in one-carbon metabolism after duodenal-jejunal bypass surgery

Jung

Lee

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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“…Finally, we did not analyze different types of alcoholic beverages. Inconsistent findings may exist because the effect of alcohol depends on the type of alcoholic beverage, as beer is a rich source of folate and vitamin B 6 , whereas red wine and spirits contain negligible amounts of these vitamins. 47 In conclusion, the present study demonstrates a strong interaction between the MTHFR 677TT genotype and lifestyle variables and an increase in the risk of elevated blood Hcy concentrations in young adult males.…”

Section: Discussionmentioning

confidence: 99%

“…Hcy acts as a key intermediate in one-carbon metabolism being metabolized through two vitamin B-dependent pathways, which are controlled by three key enzymes-methylenetetrahydrofolate reductase (MTHFR), methionine synthase and cystathionine beta-synthase 1 A high blood concentration of Hcy has been recognized as an independent risk factor for cardiovascular diseases in observational studies, [2][3][4] and is also associated with several other disorders such as neural tube defects and non-syndromic oral clefts. 5,6 Although the benefits from homocysteine lowering interventions for cardiovascular diseases have not been confirmed, 7 it is plausible that the positive effect is exclusively related to stroke risk. 8 The inconsistency related to hyperhomocysteinemia as a cause of cardiovascular diseases could result from the interactions between nutrients, metabolic and genetic factors.…”

Section: Introductionmentioning

confidence: 99%

Interactions between lifestyle and MTHFR polymorphisms on homocysteine concentrations in young adults belonging to the 1982 Pelotas Birth Cohort

et al. 2016

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BACKGROUND/OBJECTIVES: Homocysteine (Hcy) is a key intermediate in methionine metabolism. A high plasma concentration of Hcy is an independent risk factor for cardiovascular diseases among other determinants. In this study, we aimed to investigate the interactions between methylenetetrahydrofolate reductase enzyme gene (MTHFR) polymorphisms and lifestyle variables (smoking, alcohol intake and physical activity) on Hcy concentrations in a young Brazilian population. SUBJECTS/METHODS: The study population comprised 3803 individuals from the Pelotas Birth Cohort, aged 22-23 years. Allelic discrimination assays and chemiluminescence immunoassays were performed for genotyping and serum Hcy measurements, respectively. Linear regression models were used to explore the effect of gene-lifestyle interactions on Hcy concentrations. RESULTS: Men carrying the MTHFR 677TT genotype, who were also smokers and drinkers (⩾15 g of alcohol per day), had the highest concentration of Hcy (P-value for the interaction o 0.001 for smoking and 0.002 for alcohol intake). In contrast, high folate concentrations attenuated the effects of the MTHFR C677T genotype on serum Hcy concentrations (P-value for interaction o 0.001). Also, among males, blood folate concentration was the only lifestyle variable able to modify the influence of MTHFR A1298C genotypes on Hcy concentrations (P-value for the interaction o 0.001). There was no strong evidence of an interaction between the MTHFR genotypes and the lifestyle variables in women. CONCLUSIONS: In summary, our study demonstrates a sex difference in Hcy concentrations among Brazilian young adults regarding MTHFR C677T-lifestyle interactions that are worsened under conditions of low blood folate. Identification of potentially modifiable factors related to an increase in homocysteine in young adults, especially in those who are genetically susceptible, is important to prevent negative health consequences in the future.

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“…Considering plasma homocystine concentrations are highly dependent on intracellular homocysteine metabolism in liver (Schalinske and Smazal, 2012), and cystathionine is a sensitive marker of changes in flux through the transsulfuration pathway (Guttormsen et al, 2004), the greater homocystine and cystathionine indicate increased hepatic flux through this pathway in response to MET supplementation. In addition to the involvement of sulfur-containing compounds, the fact that circulating concentrations of α-aminobutyric acid also was greater in MET-supplemented cows indicates increased flux through the transsulfuration pathway (Stabler et al, 2009) Around parturition, the increased demand for nutrients and energy leads to an increase in the production reactive oxygen metabolites (ROM), the accumulation of which could deplete antioxidants and give rise to oxidative stress that may cause substantial tissue damage and render cows more susceptible to various health disorders (Bernabucci et al, 2005, Castillo et al, 2005.…”

Section: Sulfur-containing Compound Pool and Metabolismmentioning

confidence: 99%

049 Physiological and molecular mechanisms associated with performance, immunometabolic status, and liver function in transition dairy cows fed rumen-protected methionine or choline

Zhou

Vailati-Riboni

Bulgari

et al. 2016

Journal of Animal Science

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The onset of lactation in dairy cows is characterized by high output of methylated compounds in milk when sources of methyl group are in short supply. Methionine (MET) and choline (CHOL) are key methyl donors and their availability during this time may be limiting for milk production, hepatic lipid metabolism, and immune function. Supplementing rumenprotected MET and CHOL may improve overall performance and health of transition cows. observed in response to CHOL supplementation, expression of (BHMT) and MTR and BHMT enzyme activity did not change (P > 0.05). Furthermore, overall MTR enzyme activity was lower (23.5 vs. 29.6 nmol product h -1 mg protein -1 ; SEM = 2.9; P = 0.05) in CHOL cows. In terms of AA profile, MET supplementation led to greater (P < 0.01) circulating methionine and proportion of methionine in the essential AA pool, total AA, and total sulfur-containing compounds. Lysine in total AA also tends to be greater (P = 0.08) in these cows, indicating a better overall AA profile. Sulfur-containing compounds (cystathionine, cystine, homocystine, and taurine) also were greater (P < 0.05) in MET-supplemented cows, indicating an enriched sulfur-containing compound pool due to enhanced transsulfuration activity. Circulating essential AA (P = 0.06) and total AA (P = 0.03) concentrations were greater in MET cows due to greater lysine, arginine, tryptophan, threonine, proline, asparagine, alanine, and citrulline. In contrast, tryptophan and cystine were greater. Plasma 3-methylhistidine concentration was lower (P = iv 0.02) in response to CHOL, suggesting less tissue protein mobilization in these cows. Overall, results indicate that MET supplementation improves performance of transition cows through a combination of better immunometabolic status, plasma AA profile, and a reduction in oxidative stress; insufficient regeneration of MET may be one reason for the lack of effect with supplemental CHOL.

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Homocysteine Imbalance: a Pathological Metabolic Marker

Cited by 140 publications

References 98 publications

Changes in one-carbon metabolism after duodenal-jejunal bypass surgery

Changes in one-carbon metabolism after duodenal-jejunal bypass surgery

Interactions between lifestyle and MTHFR polymorphisms on homocysteine concentrations in young adults belonging to the 1982 Pelotas Birth Cohort

049 Physiological and molecular mechanisms associated with performance, immunometabolic status, and liver function in transition dairy cows fed rumen-protected methionine or choline

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