Disease relevance of CH3Ado

• Transport of a nonphosphorylated nucleoside, 5'-deoxyadenosine, by murine leukemia L1210 cells [1].
• Incubation of [3'-3H]2'-chloro-2'-deoxyuridine 5'-triphosphate (CldUTP) with adenosylcobalamin (AdoCbl), reductant, and ribonucleotide reductase from Lactobacillus leichmannii results in the production of 3H2O, uracil, tripolyphosphate, 5'-deoxyadenosine, and cob(II)alamin [2].
• Reaction of 5'-deoxyadenosine and related analogs with the 5'-methylthioadenosine cleaving enzyme of sarcoma 180 cells, a possible chemotherapeutic target enzyme [3].
• The CD spectrum gives no indication, however, of whether a certain torsion angle is the result of a rigid structure (as in AMP) or the average value of a molecule with high rotational freedom (as in 5'-deoxyadenosine) [4].
• Derivatives of 3'- and 5'-deoxyadenosine: their inhibitory activity against DNA viruses [5].

High impact information on CH3Ado

• The dehydratases are subject to reaction inactivation by the substrate glycerol which is caused by a cessation of the catalytic cycle because coenzyme B12 is not regenerated, instead 5'-deoxyadenosine and a catalytically inactive cobalamin are formed [6].
• Only a catalytic amount of S-adenosylmethionine is required for DNA repair, and no irreversible cleavage of S-adenosylmethionine into methionine and 5'-deoxyadenosine is observed during the reaction [7].
• Studying radical synthesis with [2-2H]glycine-labeled PFL, we have now found stoichiometric incorporation of a 2H atom into the 5'-deoxyadenosine (dAdo) co-product via mass and NMR spectroscopic analyses [8].
• The mechanism of action of ethanolamine ammonia-lyase, an adenosylcobalamin-dependent enzyme. The source of the third methyl hydrogen in the 5'-deoxyadenosine generated from the cofactor during catalysis [9].
• Our approach was to investigate whether hematopoietic stem/progenitor cells can be rescued from the cytotoxicity of an AMP synthesis inhibitor, L-alanosine, by 5'-deoxyadenosine, a process that requires MTAP [10].

Chemical compound and disease context of CH3Ado

• 5'-Methylthioadenosine phosphorylase-L. Substrate activity of 5'-deoxyadenosine with the enzyme from Sarcoma 180 cells [11].

Biological context of CH3Ado

• However, rather than simply binding inertly at the active site, 2-thiolglutarate elicits cobalt-carbon bond homolysis and the formation of 5'-deoxyadenosine [12].
• The kinetics of deuterium incorporation into 5'-deoxyadenosine (5'-dA) during the reaction were followed by rapid chemical quench, using HPLC and electrospray mass spectrometry to analyze the 5'-dA formed [13].
• These experiments also suggest that the presence of1in a duplex disrupts base pairing at the 5'-adjacent nucleotide and results in the thermally preferred misincorporation of purines opposite the 5'-deoxyadenosine stacked above 1 at this position [14].

Anatomical context of CH3Ado

• 5'-Deoxyadenosine had the desired ability to rescue hematopoietic progenitor cells without rescuing ATL cell lines [15].

Associations of CH3Ado with other chemical compounds

• The inactivation reaction produces acetaldehyde, the hydrazine cation radical, 5'-deoxyadenosine, and cob(II)alamin (B(12r)) in amounts stoichiometric with active sites [16].
• Adenosine uptake by these kinase-deficient cells was inhibited by adenine and 5'-deoxyadenosine, and was largely abolished in mutants devoid also of adenine phosphoribosyltransferase [17].

Gene context of CH3Ado

• All the compounds except 5'-deoxyadenosine, however, also caused the undesirable rescue of MTAP-negative ATL cell lines [15].
• However, in the presence of 5-10 microM of 5'-deoxyadenosine, colony formation of hematopoietic stem/primitive progenitors was restored [10].
• However, all computed activation enthalpies exceed the experimentally derived activation enthalpy (15 kcal/mol) associated with the rate-determining step, i.e., the hydrogen abstraction from the 5'-deoxyadenosine by the product radical [18].

Analytical, diagnostic and therapeutic context of CH3Ado

• HPLC and electrospray ionization MS analyses showed that SP lyase cleaved S-AdoMet to generate 5'-deoxyadenosine [19].
• These results support the rationale for a chemotherapy regimen of L-alanosine combined with 5'-deoxyadenosine rescue in MTAP-deficient ATL [15].

References