Development of a Standardized MRM Method for the Quantification of One Carbon Metabolism Enzymes

Author(s):  
Laura Guerrero ◽  
Alberto Paradela ◽  
Fernando J. Corrales
Author(s):  
Mario Vailati-Riboni ◽  
Fernanda Batistel ◽  
Rainie R C S Yambao ◽  
Claudia Parys ◽  
Yuan-Xiang Pan ◽  
...  

Abstract Background Post-ruminal supply of Met during the periparturient period enhances production efficiency (feed conversion to milk) in dairy cows partly through alleviation of oxidant and inflammatory status. Whether alterations in hepatic one-carbon (major contributor of antioxidants) and/or energy-metabolism contribute to these beneficial effects is unknown. Objectives Investigate alterations in hepatic one-carbon and energy metabolism and associations with plasma amino acids (AA) and production efficiency in response to enhanced post-ruminal supply of Met. Methods Holstein cows (n = 30/group) were fed during the last 28 days of pregnancy a control diet (CON) or the control plus ethyl-cellulose rumen-protected methionine (MET; 0.9 g·kg−1 of dry matter intake). Plasma (n = 15/group) and liver tissue (n = 10/group) were collected throughout the periparturient period to evaluate AA profiles, activity of TCA cycle, and one-carbon metabolism via mRNA abundance, enzyme activity, and targeted metabolomics. Results Cows in MET had greater overall (27%, P = 0.027) plasma Met concentrations, but had similar total plasma AA concentrations. Although mRNA abundance of one-carbon metabolism enzymes did not differ, hepatic activity of cystathionine β-synthase (CBS) (51.2 vs. 44.4 mmol·h−1·mg−1 protein; P = 0.032) and concentration (19%, P = 0.048) of the cellular antioxidant glutathione were greater overall in MET. mRNA abundance of aconitase 2 and fumarate hydratase was greater overall (P = 0.049), and phosphoenolpyruvate carboxykinase 1 tended (P = 0.093) to be greater overall in cows fed MET. There was a tendency (P ≤ 0.093) for greater overall hepatic concentrations of malic acid, α-ketoglutaric acid, and isocitric acid in cows fed MET. Conclusions Greater activity of CBS in response to enhanced post-ruminal supply of Met likely contributes to alleviating oxidant status by increasing concentrations of glutathione. Hence, transsulfuration plays an important role in the observed improvements in production efficiency of dairy cows during the periparturient period.


Author(s):  
Thomas D. Jackson ◽  
Daniella Hock ◽  
Catherine S. Palmer ◽  
Yilin Kang ◽  
Kenji M. Fujihara ◽  
...  

AbstractThe Acylglycerol Kinase (AGK) is a mitochondrial lipid kinase that contributes to protein biogenesis as a subunit of the TIM22 complex at the inner mitochondrial membrane. Mutations in AGK cause Sengers syndrome, an autosomal recessive condition characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy and lactic acidosis. We undertook proteomic profiling of Sengers patient fibroblasts and an AGKKO cell line to map the proteomic changes that ensue upon AGK dysfunction. This uncovered extensive remodelling of mitochondrial one-carbon metabolism enzymes and showed that inner membrane serine transporters, Sideroflexins (SFXNs), are novel substrates of the TIM22 complex. Deletion of SFXN1 recapitulates the remodelling of one-carbon metabolism observed in Sengers patient cells. Proliferation of cells lacking AGK is perturbed in the absence of exogenous serine and rescuable through addition of formate, highlighting the dysregulation of one carbon metabolism as a key molecular feature in the biology of Sengers syndrome.


2010 ◽  
Vol 80 (45) ◽  
pp. 319-329 ◽  
Author(s):  
Allyson A. West ◽  
Marie A. Caudill

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.


Proceedings ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 19
Author(s):  
Nicola Gillies ◽  
Amber M. Milan ◽  
Pankaja Sharma ◽  
Brenan Durainayagam ◽  
Sarah M. Mitchell ◽  
...  

Background: Maintaining optimal status of folate and metabolically [...]


2021 ◽  
Vol 21 (4) ◽  
pp. 206-206
Author(s):  
Felix Clemens Richter ◽  
Alexander J. Clarke

Toxicology ◽  
2021 ◽  
pp. 152803
Author(s):  
Ahlam Abuawad ◽  
Anne K. Bozack ◽  
Roheeni Saxena ◽  
Mary V. Gamble

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