Disease relevance of ASMT

• The fusion protein expressed by phage lysogens was identified on Western blots as a 165 kDA immunoreactive protein (beta-galactosidase, 110 kDa; hydroxyindole O-methyltransferase, 38 kDa) [1].

High impact information on ASMT

• 6-Formylpterin was purified by paper chromatography, and bovine pineal hydroxyindole-O-methyltransferase (S-adenosyl-L-methionine:N-acetylserotonin O-methyl-transferase; EC 2.1.1.4) was purified by flat-bed gel electrofocusing [2].
• Hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final step in melatonin synthesis [3].
• The nucleotide and deduced amino acid sequences of bovine HIOMT have been reported [3].
• Molecular cloning and nucleotide sequence of cDNA encoding hydroxyindole O-methyltransferase of bovine pineal glands [4].
• Messenger RNA for hydroxyindole O-methyltransferase (EC 2.1.1.4) was partially purified from poly(A)+ RNA isolated from bovine pineal glands by sucrose density gradient centrifugation [4].

Biological context of ASMT

• The primary structure of hydroxyindole O-methyltransferase was determined by analyzing the nucleotide sequence of the cDNAs [4].
• The cations presumably bind to HIOMT in the vicinity of the catalytic site and in some way prevent or impair the catalytic process, possibly by interfering with substrate binding to the enzyme, interfering with methyl transfer or product release after catalysis, or a combination of these effects [5].
• A search for sequences homologous to these ORFs found that the former product strongly resembles that of the 6-hydroxylation enzyme for oxytetracycline biosynthesis, and that the latter product has a weak but significant similarity to the hydroxyindole O-methyltransferase of bovine pineal gland [6].

Anatomical context of ASMT

• RNA transfer blot analysis indicated that mRNA encoding hydroxyindole O-methyltransferase was present only in the pineal gland and not in the brain, retina, and liver of cow [4].
• Northern-blot analysis revealed the presence of hydroxyindole O-methyltransferase mRNA transcripts in chicken pineal gland and retina, but not in the telencephalon [1].
• These data suggest that the 11-fold higher enzymatic activity in pineal gland is due to an accumulation of the enzyme protein, not to a high level of the mRNA and also indicate that the cloned cDNA can express an intact hydroxyindole O-methyltransferase enzyme in CHO cells [7].
• No evident HIOMT-immunoreactivity was observed in the retina and intestinal mucosa, where HIOMT has been suggested to occur [8].
• The expression of the HIOMT gene in a cluster of cells in the medial habenular nucleus is lower than that in pinealocytes of the pineal organ proper [9].

Associations of ASMT with chemical compounds

• In contrast to the inhibitory effects of cystamine on the rat enzyme, cystamine does not alter bovine hydroxyindole-O-methyltransferase and increases ovine hydroxyindole-O-methyltransferase activity [10].
• N-acetylserotonin was the best hydroxyindolic substrate for the enzyme, although other hydroxyindoles were methylated, the relative affinities being similar to values previously reported for bovine HIOMT [11].
• Purification of rat pineal hydroxyindole-O-methyltransferase using S-adenosyl-L-homocysteine agarose chromatography [12].
• Regulation of rat pineal hydroxyindole-O-methyltransferase: evidence of S-adenosylmethionine-mediated glucocorticoid control [13].
• A partially purified preparation of hydroxy-indole-O-methyltransferase (HIOMT) from bovine pineal was shown to O-methylate estradiol-17beta (E2) [14].

Other interactions of ASMT

• Likewise, S-2'-DEOXYADENOSYL-L-HOMOCYSTEINE AND S-5'-(9-(arabinofuranosyl)adenyl)-l-homocysteine had little or no effect of COMT, HMT, and HIOMT but were potent inhibtors of PNMT [15].
• Norepinephrine (10 micrometers) increased serotonin N-acetyltransferase (NAT) activity from 2.36+ / -0.23 to 6.98+ / -0.46 pmol product produced/mg protein/min (unit), without influencing tryptophan hydroxylase, 5-hydroxytryptophan decarboxylase, monoamine oxidase, or hydroxyindole-O-methyltransferase [16].
• The immunocytochemical localization for hydroxyindole O-methyltransferase (HIOMT), neuron-specific enolase (NSE) and S-100 protein in the bovine pineal gland is described in this paper [8].

Analytical, diagnostic and therapeutic context of ASMT

• Consequently, we repeated sequence analysis of the original bovine HIOMT cDNA clone, the results of which are reported here [3].
• Hypophysectomy decreases hydroxyindole-O-methyltransferase levels as compared with control animals, while dexamethasone and SAM administration restore enzyme levels toward control values [13].
• Rat pineal hydroxyindole-O-methyltransferase (HIOMT; EC 2.1.1.4) was purified by affinity chromatography using an S-adenosyl-L-homocysteine agarose column [12].
• An analysis using confocal laser microscopy together with in situ hybridization for HIOMT mRNA has shown that the expression of mRNA transcripts in the cortex is more intense than that in the medulla [9].

References