Disease relevance of Ahcy

• S-Adenosylhomocysteine hydrolase, however, is present in both rat liver and hepatoma tissue [1].
• From studies with inhibitors of membrane 5'-nucleotidase and of S-adenosylhomocysteine hydrolase, it was deduced that adenosine is produced by the latter enzyme and by cytosolic 5'-nucleotidase in normoxia, and by cytosolic and membrane 5'-nucleotidases in anoxia [2].
• The results show that the 36 amino acid sequence of Rhodobacter capsulatus S-adenosylhomocysteine hydrolase does not have a photosynthesis specific function [3].
• From the combined in vitro and perfusion studies, we conclude that S-adenosylhomocysteine hydrolase can contribute significantly to adenosine production in normoxic rat heart, but not during ischemia [4].

High impact information on Ahcy

• Induction by fungal elicitor of S-adenosyl-L-methionine synthetase and S-adenosyl-L-homocysteine hydrolase mRNAs in cultured cells and leaves of Petroselinum crispum [5].
• Amino acid sequence of S-adenosyl-L-homocysteine hydrolase from rat liver as derived from the cDNA sequence [6].
• Rat liver cDNA libraries constructed in lambda gt11 were screened for reactivity with polyclonal antibodies to native S-adenosyl-L-homocysteine (AdoHcy) hydrolase (adenosylhomocysteinase; EC 3.3.1.1) [6].
• Carbocyclic-3-deazaadenosine caused no inactivation of AdoHcyase in liver cells but caused a massive accumulation of AdoHcy, suggesting that this analogue functions as a reversible inhibitor of the enzyme [7].
• Among the analogues tested, 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosyl-3-deazaadenine were the most potent inactivators of intracellular AdoHcyase [7].

Biological context of Ahcy

• S-Adenosylhomocysteine hydrolase (AdoHcyase) catalyzes the hydrolysis of S-adenosylhomocysteine to form adenosine and homocysteine [8].
• By placing DEA into the active site of the open structure, the major forces to stabilize the closed conformation of AdoHcyase are identified as the hydrogen bonds between the backbone of His-352 and the adenine ring, and the C3'-H...C4 interaction [9].
• The polypeptide folding pattern of the catalytic domain suggests that AdoHcy molecules can travel freely to and from AdoHcyase and methyltransferases to properly regulate methyltransferase activities [10].
• The gene and pseudogenes of rat S-adenosyl-L-homocysteine hydrolase [11].
• We conclude that Nepl A inhibits S-adenosylhomocysteine hydrolase, raises cellular S-adenosylhomocysteine, decreases bulk DNA methylation, and increases hormone synthesis in GH4C1 cells [12].

Anatomical context of Ahcy

• Elicitor treatment strongly induced both mRNAs in cultured cells as well as intact leaves and led to marked increases in S-adenosyl-L-homocysteine hydrolase enzyme activity [5].
• No time-dependent leakage of S-adenosylhomocysteine hydrolase from the synaptosomes could be demonstrated [13].
• Protein carboxyl methylation in synaptic membrane of rat brain: the possible presence of adenosine-bound S-adenosyl-L-homocysteine hydrolase in the membrane [14].
• In addition, the expression of annexin VII, S-adenosyl-L-homocysteine hydrolase, elongation factor II fragment (EF-II), and adenosine deaminase was increased by H2O2-exposure in astrocytes from variously aged rats [15].
• In addition to direct in vitro inhibition of SAHH, we show that TEPA decreases protein arginine methyltransferase 1(PRMT1)-specific enzyme activity in PC12 cells and sympathetic neurons [16].

Associations of Ahcy with chemical compounds

• Inhibition of S-adenosylhomocysteine hydrolase by acyclic sugar adenosine analogue D-eritadenine. Crystal structure of S-adenosylhomocysteine hydrolase complexed with D-eritadenine [9].
• These results indicate that the inactivation of S-adenosylhomocysteinase by FSBA is the consequence of formation of a disulfide between two specific cysteine residues on each of the four identical subunits [17].
• Effects of site-directed mutagenesis on structure and function of recombinant rat liver S-adenosylhomocysteine hydrolase. Crystal structure of D244E mutant enzyme [18].
• D-eritadenine (DEA) is a potent inhibitor (IC(50) = 7 nm) of S-adenosyl-l-homocysteine hydrolase (AdoHcyase) [9].
• In contrast to the site-directed mutagenesis study, the crystal structures of human and rat AdoHcyase recently determined have shown that the carboxyl group of Asp-244 points in a direction opposite to the bound NAD molecule and does not participate in any hydrogen bonds with the NAD molecule [18].

Other interactions of Ahcy

• Other proteins that bind to the affinity column have been identified as malate and lactate dehydrogenases, cAMP-binding proteins, adenosine kinase and S-adenosylhomocysteine hydrolase [19].
• The effects of a number of nucleosides related to 5'-methylthioadenosine on the activities of S-adenosylhomocysteine hydrolase, 5'-methylthioadenosine phosphorylase, spermidine synthase and spermine synthase were investigated [20].
• After hypoosmotic treatment of the crude mitochondrial fraction and separation of this fraction on a discontinuous sucrose gradient, S-adenosylhomocysteine hydrolase and DOPA decarboxylase showed the same distribution in the gradient and were recovered in the cytoplasmic fraction [13].
• Dexamethasone administration to hypophysectomized animals does not alter either methionine adenosyltransferase activity or S-adenosylhomocysteine hydrolase activity in the adrenal gland [21].

Analytical, diagnostic and therapeutic context of Ahcy

• Catalytic mechanism of S-adenosylhomocysteine hydrolase. Site-directed mutagenesis of Asp-130, Lys-185, Asp-189, and Asn-190 [8].
• S-Adenosyl-L-homocysteine hydrolase has been purified to apparent homogeneity from rat liver by means of affinity chromatography on 8-(3-aminopropylamino)adenosine linked to Sepharose [22].
• Hypophysectomy simultaneously decreases methionine adenosyltransferase and S-adenosylhomocysteine hydrolase activity in both tissues [21].
• Trypanosoma cruzi: molecular cloning and characterization of the S-adenosylhomocysteine hydrolase [23].
• In addition, the S-adenosylhomocysteine hydrolase (EC 3.3.1.1) activity increased by 45% and 15% in liver and thymus, respectively, in the B6-deficient group compared to the pair-fed control and the control groups [24].

References