Disease relevance of N-Methylsarcosine

• The overall fold of T-protein is similar to that of the C-terminal tetrahydrofolate-binding region (residues 421-830) of Arthrobacter globiformis dimethylglycine oxidase [1].
• The effect of short-term dimethylglycine treatment on oxygen consumption in cytochrome oxidase deficiency: a double-blind randomized crossover clinical trial [2].
• Evidence of choline depletion and reduced betaine and dimethylglycine with increased homocysteine in plasma of children with cystic fibrosis [3].
• We studied the pharmacokinetics of betaine and its metabolite dimethylglycine (DMG) in healthy subjects and in three patients with homocystinuria [4].
• Seven pre-dialysis chronic renal failure patients consumed 400 mg of dimethylglycine or placebo daily for 28 days [5].

Psychiatry related information on N-Methylsarcosine

• A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder [6].

High impact information on N-Methylsarcosine

• N,N-dimethylglycine for epilepsy [7].
• Identification of folate binding protein of mitochondria as dimethylglycine dehydrogenase [8].
• Rat dimethylglycine dehydrogenase (Me2GlyDH) was used as model protein to study the biogenesis of a covalently flavinylated mitochondrial enzyme [9].
• We analyzed the folding, covalent flavinylation, and mitochondrial import of the rabbit reticulocyte lysate-translated bacterial 6-hydroxy-D-nicotine oxidase (6-HDNO) fused to the mitochondrial targeting sequence of rat liver dimethylglycine dehydrogenase [10].
• The amino acid sequences of the flavin-peptides of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver mitochondria [11].

Chemical compound and disease context of N-Methylsarcosine

• Mechanism of FAD Reduction and Role of Active Site Residues His-225 and Tyr-259 in Arthrobacter globiformis Dimethylglycine Oxidase: Analysis of Mutant Structure and Catalytic Function [12].
• When Arthrobacter P1 is grown on choline, betaine, dimethylglycine or sarcosine, an NAD(+)-dependent formaldehyde dehydrogenase is induced [13].
• Pseudomonas aeruginosa phosphorylcholine phosphatase (PChP), the product of the PA5292 gene, is synthesized when the bacteria are grown with choline, betaine, dimethylglycine, or carnitine [14].

Biological context of N-Methylsarcosine

• To increase water solubility and oral bioavailability, the N,N-dimethylglycine ester 40 was prepared [15].
• A new class of potent vascular endothelial growth factor receptor tyrosine kinase inhibitors: structure-activity relationships for a series of 9-alkoxymethyl-12-(3-hydroxypropyl)indeno[2,1-a]pyrrolo[3,4-c]carbazole-5-ones and the identification of CEP-5214 and its dimethylglycine ester prodrug clinical candidate CEP-7055 [15].
• Stepwise growth of oligo(p-phenylene oxide)s and cyclization via the Ullmann coupling reaction by using CuI/N,N-dimethylglycine afforded cyclic oligo(p-phenylene oxide)s, (n = 6-10) [16].
• Rabbit aorta and rat fundus do not display tachyphylaxis to angiotensin II (Asp1)angiotensin II) at 37 degrees C. These tissues do, however, display tachyphylaxis to [Sar1]angiotensin II (N-methylglycine 1 angiotensin II) and [dimethylglycine angiotensin II, respectively, at this temperature [17].
• The effect of dimethylglycine concentration upon the rate of the dimethylglycine dehydrogenase reaction under aerobic conditions showed nonsaturable kinetics suggesting a second low-affinity site for the substrate which increases the enzymatic rate [18].

Anatomical context of N-Methylsarcosine

• Identification of the folate-binding proteins of rat liver mitochondria as dimethylglycine dehydrogenase and sarcosine dehydrogenase. Flavoprotein nature and enzymatic properties of the purified proteins [19].
• Betaine and dimethylglycine concentrations were also significantly higher in umbilical cord than in maternal plasma [20].
• Among the compounds failing to provide adjuvant activity for ribosomes were poly(A:U), muramyl dipeptide, mycobacterial extract, dimethylglycine, methylated bovine serum albumin, sodium diethylthiocarbamate, and cetyltrimethylammonium bromide [21].
• The results suggest that the gastroprotective effect of dimethylglycine could be mediated by its free radical scavenging activity and cytoprotection of gastric mucosa [22].

Associations of N-Methylsarcosine with other chemical compounds

• Automated sequence analysis showed that the flavin-peptide from dimethylglycine dehydrogenase contained 25 amino acid residues in the following sequence: Ser-Glu-Leu-Thr-Ala-Gly-Ser- Thr-Trp-His(flavin)-Ala-Ala-Gly-Leu-Thr-Thr-Tyr-Phe-His-Pro-Gly-Ile-A sn-Leu-Lys [11].
• The flavoenzymes dimethylglycine dehydrogenase (EC 1.5.99.2) and sarcosine dehydrogenase (EC 1.5.99.1) contain covalently bound FAD linked via the 8 alpha-position of the isoalloxazine ring to the imidazole N(3) of a histidine residue (Cook, R. J., Misono, K. S., and Wagner, C. (1984) J. Biol. Chem. 259, 12475-12480) [11].
• Differential scanning calorimetric (DSC) experiments were performed on ribonuclease A and hen egg white lysozyme in the presence of varying concentrations of the osmolytes glycine, sarcosine, N,N-dimethylglycine, and betaine [23].
• Compound 21 demonstrated significant in vivo antitumor activity in numerous tumor models and was advanced into phase I clinical trials as the water-soluble N,N-dimethylglycine ester prodrug 40 (CEP-7055) [15].
• Betaine-homocysteine S-methyltransferase (BHMT) is a zinc-dependent enzyme that catalyzes the transfer of a methyl group from glycine betaine (Bet) to homocysteine (Hcy) to form dimethylglycine (DMG) and methionine (Met) [24].

Gene context of N-Methylsarcosine

• CEP-7055, a fully synthetic, orally active N,N-dimethylglycine ester of CEP-5214, a C3-(isopropylmethoxy)-fused pyrrolocarbazole with potent pan-vascular endothelial growth factor receptor (VEGFR) kinase inhibitory activity, has recently completed phase I clinical trials in cancer patients [25].
• Enzymatic properties of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver [18].
• OBJECTIVE: To study the effectiveness of dimethylglycine (DMG) on oxygen consumption (VO(2)) in children with Saguenay-Lac-Saint-Jean cytochrome-c oxidase (SLSJ-COX) deficiency (OMIM 220111) [2].
• In these studies we used normal phase HPLC with tandem mass spectrometry to determine plasma choline, betaine, and dimethylglycine in children with CF (n = 34) and healthy control children without CF (n = 15) [3].
• The cation-exchange chromatography separates dimethylglycine from other compounds which can serve as substrates for dimethylglycine dehydrogenase [26].

Analytical, diagnostic and therapeutic context of N-Methylsarcosine

• The method of quantitating N,N-dimethylglycine involves cation-exchange high-performance liquid chromatography and detection of dimethylglycine with dimethylglycine dehydrogenase [26].
• In a crossover study, either a placebo paste or N,N-dimethylglycine was administered orally at a dose rate of 1.2 mg/kg twice daily for five days to six thoroughbred horses, with bodyweights ranging from 424 to 492 kg [27].

References