Transmethylation Research Articles

Methionine kinetics and first pass disappearance in healthy adolescents

Methionine, an indispensable amino acid serves as precursor for important substrates. There are no data on methionine first‐pass disappearance (SU) and whole body kinetics in healthy children receiving methionine by the oral or intravenous route. We studied four healthy adolescents, (age 15.0±1.2 y; wt 51.9±6.3 kg) receiving a 2 day dietary period providing adequate energy and protein intakes. On day 3 the subjects received a dual, primed, 8h, continuous tracer infusion of L‐[13C]‐ and L‐[2H3]‐methyl methionine by the intravenous and enteral routes respectively, while consuming small isocaloric and isonitrogenous meals every 30 min. On the next day the route of tracer administration was reversed. HCY/Meth ratios were 0.89 and 0.66 respectively for the oral and IV tracers, while the SU of 13C‐ and 2H3‐methionine labels were 29±0.13% and 31±0.13 % respectively. Methionine transmethylation (TM), remethylation (RM) and transulfuration (TS) were 33±10, 14±5 and 18±6, and 23±3, 11±2 and 11±4 µmol/kg/h respectively, for the oral and IV tracer routes using HCY enrichment as precursor; and 29±19, 13±5 and 16±5 and 15±4, 8±2 and 7±4 µmol/kg/h respectively, for the oral and IV tracer routes when methionine enrichment was used. In this preliminary data, methionine SU in healthy adolescents was between 29‐31% and about 50% of methionine plasma flux was utilized for TM when the tracer was given by the oral route, while 22 and 28% were utilized for TS and RM respectively. Hence, the intestinal tract is a major site of whole body methionine TM. NIH DK‐62363, T32 HD‐007445, Ajinomoto 3‐ARP; USDA/ARS 25337387

Methionine cycle kinetics and arginine supplementation in endothelial dysfunction of ESRD.

To investigate the effect of arginine supplementation on metabolic pathways involved in endothelial dysfunction of end stage renal disease (ESRD), we conducted a study on 11 ESRD patients age 49±16; wt 93±26 kg receiving an adequate protein and energy intake for 1week, followed by a primed, continuous, 9h infusion (4h fast;5h fed) of L-[1-13C] methionine, L-[2H3] methyl methionine, and determination of flow mediated vasodilatation (FMD). After a break period, they received daily arginine supplementation of 21g, for 4weeks, and the studies were repeated. Diets were isonitrogenous. The rates of methionine transmethylation (TM), Transulfuration (TS) and Remethylation RM are shown in Table 1. There was an effect of the metabolic period, fast vs. fed on remethylation rates for the arginine supplemented diet, and on the TS rates for the control and arginine supplemented periods. However, there was no effect of arginine supplementation on the rates of TM, TS, RM or on FMD. Arginine supplementation does not affect methionine cycle metabolism. NIH DK62363, Ajinomoto 3ARP Program. Table 1. Methionine cycle kinetics during control diet and arginine supplementation.

Homocysteine clearance and methylation flux rates in health and end-stage renal disease: association with S-adenosylhomocysteine.

Hyperhomocysteinemia is a risk factor for cardiovascular disease and occurs frequently in end-stage renal disease (ESRD), but its pathogenesis is poorly understood. We aimed to evaluate one-carbon flux rates of methionine and homocysteine (Hcy) in ESRD patients and healthy controls. Transmethylation (TM), remethylation (RM), and transsulfuration (TS), as well as Hcy clearance by TS (i.e., TS/plasma total Hcy concentration) and by RM (i.e., RM/plasma total Hcy concentration) were evaluated in relation to body composition, vitamins, and S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet) levels. After a fixed protein diet for 3 days, primed-continuous infusion of [(2)H(3)-methyl-1-(13)C]methionine was performed in the postabsorptive state in 12 hemodialysis patients and 16 healthy volunteers. Hcy clearance by TS (-80%, P < 0.001) and by RM (-77%, P < 0.001) in ESRD patients was decreased compared with healthy controls. The absolute flux rates of TM (-27%, P < 0.01) and RM (-28%, P = 0.02) were lower in the ESRD patients. After adjustment for age, TS was not significantly reduced. Whole blood AdoHcy was significantly elevated in ESRD and was a significant determinant of TM (standardized beta = -1.24, P = 0.01) and RM (standardized beta = -1.43, P = 0.03). In conclusion, patients with ESRD have impaired Hcy clearance by TS and RM. Elevated whole blood AdoHcy levels are associated with impaired RM and TM flux rates in these patients, and AdoHcy may be a key regulatory compound in one-carbon flux.

Identification of an Original Non-Terpenoid Varnish from the Early 20th Century Oil Painting “The White Horse” (1929), by H. Menzel

Different mass spectrometric approaches were used to identify an original non-terpenoid varnish. Direct temperature-resolved MS and pyrolysis-GC/MS mainly showed the phenolic components, whereas thermally assisted (trans)methylation with tetramethylammonium hydroxide (TMAH) strongly enhanced the evidence for tung oil as part of the varnish. Transethylation studies of the fatty acids confirmed the TMAH data. The degree of hydrolysis of the oil network was found to be low. No evidence was found for a direct link between the drying oil and phenolic resin. On the basis of the MS information, the aged varnish is identified as an open-structure tert-butylphenol-formaldehyde resin which entangles the tung oil polymer.

Preparation and assignment of configuration of 1-benzoyl- (2 S)- tert-butyl-3-methyl-perhydropyrimidin-4-one. Useful starting material for the enantioselective synthesis of α-substituted β-amino acids

(S)-Asparagine, an inexpensive β-amino acid was converted into the title heterocycle (+)- 1 in very good overall yield. The highly selective trans methylation of (+)- 1-Li, and the hydrolysis of the resulting adduct afforded ( R)-α-methyl-β-alanine, allowing the assignment of the ( S) configuration in (+)- 1.

More on transmethylation and the liver

More on transmethylation and the liver

1-13C; methyl-2H3]methionine kinetics in humans: methionine conservation and cystine sparing

Methionine (Met) conservation in healthy young adult men (4/diet group) was explored by supplying one of the following three L-amino acid based diets: 1) adequate Met but no cystine; 2) neither Met nor cystine; or 3) no Met but cystine supplementation. After 5 days, subjects received a continuous intravenous infusion of L-[1-13C; methyl-2H3]Met for 5 h while the diet was given as small isocaloric isonitrogenous meals. Estimates were made of rates of Met incorporation into protein synthesis (S) and release from body proteins (B), transmethylation (TM), remethylation of homocysteine (RM), and transsulfuration (TS). For the adequate Met diet, the rates were S = 24 +/- 2, B = 18 +/- 1, TM = 12.4 +/- 1.7, RM = 4.7 +/- 1.1, and TS = 7.6 +/- 0.6 (SE) mumol.kg-1.h-1. The sulfur amino acid-devoid diet significantly (P less than 0.05) reduced S, TM, RM, and TS. Supplementation of this diet with cystine reduced Met oxidation (P = 0.05). Therefore, two loci are quantitatively important regulatory points in Met conservation in vivo: 1) the distribution of Met between the pathways of protein anabolism and TM (Met locus) and 2) the distribution of homocysteine between RM and TS (homocysteine locus).

Quantitative study in vivo of methionine cycle in humans using [methyl-2H3]- and [1-13C]methionine.

Kinetic aspects of body methionine (MET) metabolism were examined in healthy young men during the fed and postabsorptive (PA) states. Rates of MET incorporation (S) into and release (B) from body proteins; transmethylation (TM); and remethylation (RM) and transsulfuration (TS) of homocysteine (HCY) were estimated with the aid of a 5-h constant intravenous infusion of [methyl-2H3]- and [1-13C]methionine. The isotopic data (plasma methionine labeling and 13C enrichment of expired air) were submitted to a stochastic model of amino acid metabolism. During the fed state, the subjects (n = 4) received, at 20-min intervals, small isonitrogenous isocaloric meals containing a complete L-amino acid mixture supplying MET at a rate equivalent to 198 mumol.kg body wt-1.day-1. The PA subjects (n = 4) received the isotope after a 10-h overnight fast. For the PA group, the components of MET metabolism were as follows: S, 20 +/- 0.5; B, 24 +/- 0.5; TM, 5.8 +/- 0.6; RM, 1.8 +/- 0.4; and TS, 4.0 +/- 0.4 (+/-SE) mumol.kg-1.h-1. During the fed state the values were S, 26 +/- 2.5; B, 18 +/- 2; TM, 14 +/- 1.3; RM, 5.7 +/- 0.9; and TS 8.3 +/- 0.6 mumol.kg-1.h-1. The meal-induced changes in B, TM, RM, and TS were significant (P less than 0.05). Comparison of the partitioning of MET between S and TM (these two pathways of MET disposal constitute the "methionine locus") in the PA and in the fed states indicates that the MET locus is of regulatory importance in MET homeostasis. A twofold increase in the partitioning of MET to TM was observed in the fed state. The increase in HCY recycling, relative to TS (these two pathways of HCY disposal constitute the "HCY locus"), in the fed state did not reach statistical significance when compared with the PA state. Total daily TM are estimated to be 238 +/- 22 mumol/kg. This is similar to the estimate generated by the methyl balance model of Mudd and Poole (Metabolism 24: 721, 1975) which approximated 241 mumol/kg.

Über eine thermische Transmethylierungsreaktion bei Flavon-5-methylethern / On a Thermal Transmethylation Reaction with Flavon-5-methylethers

Upon heating to 300 °C partial luteolinemethylethers undergo transmethylation. A reaction mechanisme is put foreward.

THE EFFECT OF THE DIETARY LEVEL OF METHIONINE ON THE RATE OF TRANSMETHYLATION REACTIONS IN VIVO

THE EFFECT OF THE DIETARY LEVEL OF METHIONINE ON THE RATE OF TRANSMETHYLATION REACTIONS IN VIVO

THE RELATION OF TRANSMETHYLATION TO ANSERINE

THE RELATION OF TRANSMETHYLATION TO ANSERINE