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AdoHcy

SMM synthesis is mediated by the enzyme methionine S-methyltransferase (MMT) through the essentially irreversible, AdoMet-mediated methylation of methionine.48"5 Both MMT and SMM are unique to plants 48,50 The opposite reaction, in which SMM is used to methylate homocysteine to yield two molecules of methionine, is catalyzed by the enzyme homocysteine S-methyltransferase (HMT).48 Unlike MMT, HMTs also occur in bacteria, yeast, and mammals, enabling them to catabolize SMM of plant origin, and providing an alternative to the methionine synthase reaction as a means to methylate homocysteine. Plant MMT and HMT reactions, together with those catalyzed by AdoMet synthetase and AdoHcy hydrolase, constitute the SMM cycle (Fig. 2.4).4... [Pg.24]

Figure 2.10 Structures of mammalian DNA methylases. (a) Ribbon representation of the structure of the tetrameric complex formed between the C-terminal domain of Dnmt3a2 (orange) and the C-terminal domain of Dnmt3L (green) (PDB code 2qrv). The AdoHcy molecules are colored cyan. Figure 2.10 Structures of mammalian DNA methylases. (a) Ribbon representation of the structure of the tetrameric complex formed between the C-terminal domain of Dnmt3a2 (orange) and the C-terminal domain of Dnmt3L (green) (PDB code 2qrv). The AdoHcy molecules are colored cyan.
CS-cytosine methylation of DNA mechanistic implications of new ystal structures for HhaL methyitransferase-DNA-AdoHcy complexes. Journal of Molecular Biology, 261 (5), 634-645. [Pg.56]

Figure8.5 Mechanism of cytosine methylation. For a description see text. AdoHcy S-Adenosylhomocysteine. Figure8.5 Mechanism of cytosine methylation. For a description see text. AdoHcy S-Adenosylhomocysteine.
AASA a-aminoadipic semialdehyde, AdoHcy S-adenosylhomocysteine, AdoMet S-adenosylmethionine, Ala alanine, Arg arginine, alle alloisoleucine, Apo aminopiperidone, ASA argininosuccinate,... [Pg.81]

The loss of a methyl group from AdoMet in each of the reactions yields S-ad-enosylhomocysteine (AdoHcy) and this is subsequently hydrolysed to adenosine and Hey by AdoHcy-hydrolase. Hey sits at a metabolic branch point and can be remethylated to methionine by way of two reactions. One is the 5-methyltetrahydrofo-late dependent reaction catalysed by methionine synthase, which itself is reductively methylated by cobalamin (vitamin B12) and AdoMet, requiring methionine synthase reductase. 5-Methyltetrahydrofolate is generated from 5,10-methylenetetrahydrofo-late (MTHF) by MTHF reductase. The second remethylation reaction is catalysed by betaine methyltransferase, which is restricted to the liver, kidney and brain, while methionine synthase is widely distributed. [Pg.91]

The metabolic control of methionine metabolism is complex and involves, for example, changes of enzyme levels in particular tissues, mechanisms linked to the kinetic properties of the various enzymes and their interaction with metabolic effectors [6, 7]. A particularly important metabolic effector is AdoMet. This inhibits the low Km isoenzymes of MAT, and MTHF reductase, inactivates betaine methyltransferase, but activates MAT III (the high-Km isoenzyme) and cystathionine /1-synthase. Therefore, high methionine intake and thus higher AdoMet levels favour trans-sulphuration, and when levels are low methionine is conserved. AdoHcy potently inhibits AdoMet-dependent methyltransferases and both Hey remethylating enzymes. Another important control mechanism is the export of Hey from cells into the extracellular space and plasma, which occurs as soon as intracellular levels increase [8]. [Pg.92]

The laboratory measurement of AdoMet and AdoHcy is not routinely performed, but plays an increasing role in studies of pathogenesis of elevated Hey as well as the differential diagnosis of hypermethioninaemia due to deficiency of MAT, glycine methyltransferase or AdoHcy hydrolase. [Pg.93]

Until the middle 1990s, AdoMet and AdoHcy had been studied almost exclusively in tissues or cerebrospinal fluid (CSF). Recent studies have shown that AdoMet and AdoHcy are readily detectable in isolated erythrocytes or whole blood, and reduced levels of AdoMet have been reported in whole blood from patients with coronary artery disease [18]. Application of HPLC with fluorescence detection has allowed the detection of these two compounds in plasma, although levels are in the nanomolar range and clearly much lower than those in tissues [19, 20]. Clear increases were shown in normal subjects following the administration of methionine [20] or AdoMet [21]. Subsequently, several studies have confirmed the ability to measure... [Pg.93]

AdoHcy comprises an adenosyl moiety attached to Hey through the latter s S atom. Its molecular weight is 384.4 and it absorbs ultraviolet light strongly with a maximum absorbance (Amax) at 260 nm at pH 7. [Pg.94]

Measurement of AdoMet and AdoHcy in Plasma and CSF by HPLC with Fluorescence Detection... [Pg.103]

The reaction of AdoMet and AdoHcy with monochloroacetaldehyde produces the etheno derivatives, which are strongly fluorescent (Fig. 2.2.6). These derivatives are separated by isocratic HPLC and detected and quantified by fluorescence. Our methods have been modified from those of Wagner et al. [28]. [Pg.103]

A minimum of 2 ml EDTA blood is placed immediately on ice and centrifuged within 30 min at 2000 xg for 5 min at 4°C. Plasma is immediately deproteinised by adding 1 ml to 0.625 ml of 10% 4 and mixing thoroughly by vortex. The mixture is frozen and stored at -70°C until analysis. 1-ml aliquots of pooled plasma collected from healthy subjects are prepared and stored in the same way and are used to prepare AdoMet and AdoHcy calibration standards to allow for matrix effects and also as an internal quality control. CSF is collected in plain tubes and kept at -70°C until analysis. [Pg.103]

Fig. 2.2.6 Mechanism of the derivatisation of S-adenosylmethionine (AdoMet), S-adenosylho-mocysteine (AdoHcy) and chloroacetaldehyde... Fig. 2.2.6 Mechanism of the derivatisation of S-adenosylmethionine (AdoMet), S-adenosylho-mocysteine (AdoHcy) and chloroacetaldehyde...
Accurately weigh 1.18 mg of S-adenosylmethionine hydrogen sulphonate (Boeh-ringer Mannheim, cat. no. 102 407, MW 496.2 g/mol) or 1.32 mg of S-adenosylhomocysteine (Sigma cat. no. A 9384, MW 384.4 g/mol). These are dissolved in demineralised water (usually approximately 5 ml) to give a concentration for AdoMet of 0.342 mmol/1 (after correction for the purity declared for the particular batch) and for AdoHcy of 0.686 mmol/1. These solutions are immediately diluted ten-fold with 0.4 mol/1 perchloric acid and can be stored in aliquots at -20 C for at least 6 months. [Pg.104]

AdoHcy Phenomenex, Gemini C-18, 3 pm (150x3 mm) with a guard column (4x2 mm) containing the same packing material. [Pg.105]

For both AdoMet and AdoHcy, calibration is performed using three standards 53, 106 and 210 nmol/1 for AdoMet and 40, 80 and 160 nmol/1 for AdoHcy, each added to pooled plasma supernatant fluid, plus a pooled plasma blank. Higher concentrations can be used if sample levels are expected to be high. [Pg.105]

Neither AdoMet nor AdoHcy have so far been included in any external quality control scheme. Control samples are not commercially available. A pooled plasma sample is included in each batch as internal quality control. [Pg.105]

This depends greatly on the sensitivity of the fluorimeter used, but the following levels should be achievable AdoMet and AdoHcy, 2-5 nmol/1 per sample. [Pg.105]

AdoMet and AdoHcy are separated and measured as their etheno derivatives using reverse-phase HPLC with isocratic elution in separate runs, using ion-pairing for AdoMet. In both runs the column is flushed with 100% acetonitrile followed by reequilibration with the mobile phase between sample injections. [Pg.105]

Concentrations of AdoMet or AdoHcy in plasma samples are determined by dividing the peak area in the unknown run by the slope of the calibration line and multiplying by 1.625 to allow for the dilution of plasma. Thus, AdoMet or AdoHcy concentration = Area/slope x 1.625. (see Fig. 2.2.7). [Pg.106]

Chromatography of one or two samples spiked with AdoMet (210 nmol/1) and AdoHcy (160 nmol/1) is performed within each batch to aid in identification of peaks. Typical elution times are 28-34 min for etheno-AdoMet and 8-10 min for etheno-AdoHcy. The separations obtained for AdoMet and AdoHcy obtained with a normal plasma sample are shown in Fig. 2.2.8. [Pg.106]

AdoMet and AdoHcy are unstable in neutral and alkaline solution they must be kept acidified. [Pg.106]

Fig. 2.2.7 a Standard curve of AdoMet in human plasma, b Standard curve of AdoHcy in plasma... [Pg.107]

Care needs to be taken in distinguishing the true AdoMet and AdoHcy peaks from closely eluting substances. [Pg.107]

Measurement of AdoMet and AdoHcy Using Plasma HPLC and Tandem Mass Spectrometry... [Pg.107]


See other pages where AdoHcy is mentioned: [Pg.16]    [Pg.20]    [Pg.21]    [Pg.26]    [Pg.27]    [Pg.36]    [Pg.46]    [Pg.172]    [Pg.345]    [Pg.80]    [Pg.81]    [Pg.94]    [Pg.104]    [Pg.104]    [Pg.104]    [Pg.105]    [Pg.105]    [Pg.105]    [Pg.106]    [Pg.107]    [Pg.107]   
See also in sourсe #XX -- [ Pg.211 ]




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