Disease relevance of Ahcy

• Neplanocin A. A potent inhibitor of S-adenosylhomocysteine hydrolase and of vaccinia virus multiplication in mouse L929 cells [1].
• Severe T and B cell lymphopenia was accompanied by a pronounced accumulation of 2'-deoxyadenosine and dATP in the thymus and spleen, and a marked inhibition of S-adenosylhomocysteine hydrolase in these organs [2].
• Consistent with its potent inhibition of S-adenosylhomocysteine hydrolase, 3-deazaneplanocin A displayed excellent antiviral activity in cell culture against vesicular stomatitis, parainfluenza type 3, yellow fever, and vaccinia viruses [3].
• A reversible s-adenosyl-L-homocysteine hydrolase inhibitor ameliorates experimental autoimmune encephalomyelitis by inhibiting T cell activation [4].
• S-Adenosyl-L-homocysteine hydrolase inhibitor mediates immunosuppressive effects in vivo: suppression of delayed type hypersensitivity ear swelling and peptidoglycan polysaccharide-induced arthritis [5].

High impact information on Ahcy

• Methylation of Vav1 and IL-2 production were reduced by inhibiting S-adenosyl-L-homocysteine hydrolase, an enzyme that regulates cellular transmethylation [6].
• The protein components of the corresponding human and murine alpha-complexes differ in a complementary manner: the previously described 39 kDa poly(C) binding protein (PCBP) present in the human alpha-complex is replaced in the mouse alpha-complex by a 48 kDa cytoplasmic poly(CU) binding protein (CUBP) [7].
• The mouse lethal nonagouti (a(x)) mutation deletes the S-adenosylhomocysteine hydrolase (Ahcy) gene [8].
• Second, pretreatment of macrophages with periodate-oxidized adenosine (to inhibit S-adenosylhomocysteine hydrolase) prevented the subsequent metabolism of c3Ado to S-3-deazaadenosylhomocysteine but did not diminish the effects of c3Ado on phagocytosis or microfilaments [9].
• First, periodate-oxidized adenosine and 3-deaza(+/-)aristeromycin, two other inhibitors of S-adenosylhomocysteine hydrolase that caused greater increases in macrophage S-adenosylhomocysteine than did c3Ado, had no effect on either phagocytosis or microfilaments [9].

Chemical compound and disease context of Ahcy

• In the present experiments, a mutant clone (Sahn 12) with 11-13% of wild-type S-adenosylhomocysteine hydrolase activity was selected from the murine T lymphoma cell line R 1.1 after mutagenesis and culture in adenosine, deoxycoformycin, uridine and homocysteine thiolactone-supplemented medium [10].

Biological context of Ahcy

• Analysis of 123 progeny of an interspecific backcross between a laboratory stock, AN, and Mus spretus using a rat cDNA probe revealed the presence of at least two other Ahcy-related sequences segregating independently in the mouse genome [11].
• Identification of a major hepatic copper binding protein as S-adenosylhomocysteine hydrolase [12].
• Moreover, human placental SAHH, like mouse liver CuBP, has a single high affinity copper binding site per 48-kDa subunit [12].
• S-adenosylmethionine synthetase is overexpressed in murine neuroblastoma cells resistant to nucleoside analogue inhibitors of S-adenosylhomocysteine hydrolase: a novel mechanism of drug resistance [13].
• Accordingly, poor energy supply by the insufficient SAHH enzymatic activity in the brain postnatally may be responsible for epileptogenesis in this animal model [14].

Anatomical context of Ahcy

• Consistent with the results using whole cytosols, the purified CuBP from the brindled mouse showed decreased copper binding in both the tetramer and monomer fractions from Superose [15].
• Selective inhibition of T cell activation by an inhibitor of S-adenosyl-L-homocysteine hydrolase [16].
• 3-Deazaadenosine. S-adenosylhomocysteine hydrolase-independent mechanism of action in mouse lymphocytes [17].
• This selective suppression was also observed when enriched murine T and B cells were stimulated with mitogens, although S-adenosyl-L-homocysteine (AdoHcy), the substrate of AdoHcyase, was similarly elevated in both populations [16].
• The S-adenosyl-L-homocysteine hydrolase inhibitor 3-deazaadenosine (3-DAA) modulates antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (AD phi) by mouse spleen effector cells and antibody-coated erythrocyte target cells [18].

Associations of Ahcy with chemical compounds

• The changes in the AdoMet/AdoHcy ratio could not be attributed to increases in the activities of methionine adenosyltransferase II or S-adenosylhomocysteine hydrolase in the brain tissue of these mice [19].
• The copper binding activity of SAHH is proposed to play a significant role in the intracellular distribution of copper, and SAHH enzymatic activity may influence copper metabolism through its role in cysteine biosynthesis from methionine [12].
• Effect of 2'-deoxycoformycin infusion on S-adenosylhomocysteine hydrolase and the amount of S-adenosylhomocysteine and related compounds in tissues of mice [20].
• S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase in various tissues of mice given injections of 9-beta-D-arabinofuranosyladenine [21].
• This paper demonstrates that N6-methyladenosine (6-methylaminopurine ribonucleoside) will condense in vitro with homocysteine to form S-N6-methyladenosylhomocysteine in a reaction catalyzed by mouse liver S-adenosylhomocysteine hydrolase [22].

Other interactions of Ahcy

• A comparison of levels of the ADA substrates, adenosine and 2'-deoxyadenosine, as well resulting dATP levels and S-adenosylhomocysteine hydrolase inhibition in bone marrow and spleen suggested that dATP accumulation in ADA-deficient spleens may be responsible for impaired B cell development [23].
• E1 mice epilepsy shows genetic polymorphism for S-Adenosyl-L-homocysteine hydrolase [14].
• Effect of adenosine analogues on protein carboxylmethyltransferase, S-adenosylhomocysteine hydrolase, and ribonucleotide reductase activity in murine neuroblastoma cells [24].
• To decrease plasma Hcy, dietary supplementation with 3-deazaadenosine (DZA), the S-adenosylhomocysteine hydrolase inhibitor, was administered to cystathionine beta-synthase (CBS) knockout (KO) mice [25].

Analytical, diagnostic and therapeutic context of Ahcy

• The potent irreversible inhibitor of S-adenosyl-L-homocysteine hydrolase (Z)-5'-fluoro-4',5'-didehydro-5'-deoxyadenosine (MDL 28,842) was examined for its effect on the development and treatment of collagen-induced arthritis in mice [26].
• Western blots indicated that the liver contains approximately 12 times more SAHH than the kidney, which in turn contains approximately 5 times more SAHH than the brain [27].
• Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 11. Molecular dissections of neplanocin A as potential inhibitors of S-adenosylhomocysteine hydrolase [28].
• Antiviral drug therapy of filovirus infections: S-adenosylhomocysteine hydrolase inhibitors inhibit Ebola virus in vitro and in a lethal mouse model [29].
• Inhibition of S-adenosyl-L-homocysteine hydrolase induces immunosuppression [30].

References