Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel type of N-acetyltransferase, clearly different from the nuclear and cytosolic polyamine N-acetyltransferases of mammals, was recently found in the intestinal nematode Ascaris suum. The occurrence of this putrescine N-acetylating enzyme has also been noted in the filarial parasite Onchocerca volvulus. The enzyme was partially purified from adults of O. volvulus and A. suum by chromatography on DEAE-cellulose and cadaverine-Sepharose. Substrate specificities of the filarial enzyme resemble those of the N-acetyltransferase from A. suum, with respect to its preference for putrescine and other diamines above polyamines and histones. Additionally, both nematode enzymes acetylated histamine, whereas dopamine and serotonin were not accepted as substrates. The activities of the N-acetyltransferase from O. volvulus and A. suum were potently inhibited by the drug berenil; the type of inhibition was competitive with respect to putrescine. The inhibition constants for berenil were determined as 4.2 and 1.2 microM for the enzymes of O. volvulus and A. suum, the Km values for putrescine were found to be 330 microM and 250 microM, respectively. Putrescine N-acetyltransferase is discussed as a regulatory step in the degradation of excessive polyamines via polyamine oxidase to putrescine. At this branching point, putrescine is retained in the cell for de novo synthesis of spermidine and spermine, catabolized via diamine oxidase or acetylated to a suitable transport product for excretion.
Mol Biochem Parasitol 1990 Jan 01
PMID:Putrescine N-acetyltransferase in Onchocerca volvulus and Ascaris suum, an enzyme which is involved in polyamine degradation and release of N-acetylputrescine. 232 51

An inbred mouse model for the human N-acetylation polymorphism has been used to investigate the biochemical basis for the arylamine N-acetylation polymorphism and the relationship between the cytosolic enzymes arylamine N-acetyltransferase (NAT), arylhydroxamic acid N,O-acyltransferase, and N-hydroxyarylamine O-acetyltransferase. Biochemical studies of partially purified NAT from rapid and slow acetylator mice revealed identical molecular weights of 31,500, activation energies of 21,000 cal/mol, equivalent affinities for acetyl coenzyme A, broad pH optima, the presence of an active site sulfhydryl group, and similar behavior during purification with anion exchange, gel filtration, and hydrophobic interaction chromatography. The enzymes differed in inhibition by hydrogen peroxide and dithiobis(2-nitrobenzoic acid). These observations taken in conjunction with previous investigations indicate that the rapid and slow mouse NAT enzymes are isozymes with minimal structural differences. NATs from rapid and slow acetylator mice were purified more than 10,000-fold by the following sequence of methods: homogenization and fractional centrifugation, protamine sulfate precipitation, and chromatography on DEAE-Trisacryl M, Sephadex G-100, Amethopterin-AH-Sepharose 4B, butyl agarose, and Sephacryl S-200, with a 15-25% recovery. NAT from B6 mice was purified to greater than 95% purity, as judged by silver staining of sodium dodecyl sulfate-polyacrylamide gels. Although only NAT appeared to be subject to a genetic polymorphism as evidenced by N-acetylation activities in liver cytosol, the purified NAT protein possessed arylhydroxamic acid N,O-acyltransferase, N-hydroxyarylamine O-acetyltransferase, and NAT activities. Thus, the cytosolic N-acetyltransferase of mouse liver may catalyze N-, O-, and N,O-acetyltransfer reactions through a common acetylated intermediate of a single protein.
Mol Pharmacol 1989 May
PMID:Purification and biochemical characterization of hepatic arylamine N-acetyltransferase from rapid and slow acetylator mice: identity with arylhydroxamic acid N,O-acyltransferase and N-hydroxyarylamine O-acetyltransferase. 272 69

The activity of arylalkylamine N-acetyltransferase (EC 2.3.1.87), the rate-controlling enzyme in melatonin synthesis is stimulated approximately equal to 100-fold by an adrenergic cyclic AMP mechanism in both neonatal and adult rat pineal glands. This stimulation is blocked in the adult gland by the depolarizing agents ouabain (1 microM) and K+ (80 mM) (Parfitt, A., Weller, J.L., Klein, D.C., Sakai, K.K., and Marks, B.H. (1975) Mol. Pharmacol. 11, 241-255). In the present study pineal glands obtained from prenatal to adult rats were used; it was found that K+ (80 microM) inhibited the adrenergic stimulation of N-acetyltransferase activity at all ages but that ouabain (1 nM to 1 mM) treatment was not inhibitory early in development. In contrast, in the neonate, ouabain (1-100 nM) enhanced adrenergic induction of N-acetyltransferase activity, and ouabain treatment alone (1-1000 nM) stimulated N-acetyltransferase activity. A small stimulation was also seen at one concentration (1 nM) in the adult. Analysis of the development of high affinity ouabain binding sites and Na+,K+-ATPase activity in the intact pineal gland indicated that the developmental pattern of both resemble the development of ouabain inhibition of the adrenergic stimulation of N-acetyltransferase activity. All are low for the first few days of life, gradually increase during the next 3 weeks of life, and then approach adult levels. Similarly, ouabain (1 nM to 1 mM) had no effect on 86Rb uptake in the 2-day-old gland but blocked (IC50 congruent to 20 nM) 86Rb uptake in the adult gland. These findings indicate ouabain probably has little inhibitory effect on the norepinephrine stimulation of N-acetyltransferase activity in the neonatal because a high affinity ouabain binding form of Na+,K+-ATPase activity, similar to the alpha + form identified in rat brain, is at very low levels in the pinealocyte. Accordingly, it appears that an ouabain-insensitive mechanism in the neonatal gland maintains membrane potential and that this mechanism plays a less important role in the adult. The explanation of why ouabain alone stimulates N-acetyltransferase activity and why it enhances the effects of norepinephrine in the neonatal pineal gland might be that ouabain acts on surviving neural elements present in the gland to cause the net release of a transmitter, perhaps norepinephrine, which then stimulates N-acetyltransferase activity.
 ...
PMID:Developmental study of ouabain inhibition of adrenergic induction of rat pineal serotonin N-acetyltransferase (EC 2.3.1.87). 282 93

Ouabain inhibits (IC50 congruent to 200 nM) the congruent to 100-fold adrenergic cyclic AMP stimulation of rat pineal arylalkylamine N-acetyltransferase (EC 2.3.1.87, serotonin N-acetyltransferase, NAT) activity in intact pineal glands. In the present study, ouabain binding sites in pineal membranes were characterized in detail and compared to sites in isolated pinealocytes, which mediate the inhibition of Na+,K+-ATPase, as indicated by 86Rb uptake and norepinephrine (NE) stimulation of NAT activity. High affinity ouabain-binding sites were identified in crude preparations of pineal membranes (Kd congruent to 14 nM; Bmax congruent to 4 pmol/mg of protein) and similar sites were also found in ovine and bovine pineal tissue. The ouabain Kd value for the rat pineal binding sites was similar to the estimated ouabain IC50 values for 86Rb uptake and the NE stimulation of NAT activity in intact rat pinealocytes. In addition, the relative orders of potency of four cardiac glycosides in displacing [3H]ouabain from high affinity binding sites and inhibiting both 86Rb uptake and NE stimulation of NAT activity were the same (acetyldigitoxin greater than ouabain greater than digitoxin greater than strophanthidin). The similarities in the characteristics of the high affinity [3H]ouabain-binding sites and the sites involved in the inhibition of 86Rb uptake and stimulation of NAT activity indicate that an alpha +-like Na+,K+-ATPase mediates the inhibitory effects of ouabain on the adrenergic induction of pineal NAT activity.
Mol Pharmacol 1987 Dec
PMID:Characterization of the alpha +-like Na+,K+-ATPase which mediates ouabain inhibition of adrenergic induction of N-acetyltransferase (EC 2.3.1.87) activity: studies with isolated pinealocytes. 282 93

Cytosolic liver acetyl-CoA:arylamine N-acetyltransferase (EC 2.3.1.5) from homozygous rapid acetylator rabbits (strain III/J) was purified to homogeneity as judged by gel filtration sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis and isoelectrofocusing. The isoelectric point was estimated to be 5.2. The molecular weight was determined to be 33,500 by sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis and 33,000 by Sephacryl S-200 gel filtration. The amino acid composition is reported and 16 tryptic peptides were sequenced by Edmann degradation, including a peptide from which a very specific oligonucleotide probe can be synthesized. The enzyme contained neither amino sugars nor cofactors. A broad pH optimum from pH 5.9 to 8.6 was observed. N-Acetyltransferase activity showed a strong dependency on the salt concentration. From the influence of the basicity of the acceptor amine on the maximum velocity, it was concluded that the formation of the covalent acetyl-enzyme intermediate is the rate-limiting step in the N-acetyltransferase-catalyzed acetylation of amines. The covalent intermediate reacts, then, in a fast step with the acceptor amine, when using aniline derivatives with pKa values ranging from 5.65 to 1.74. However, with the weakly basic 4-nitroaniline, the acetyltransfer from the catalytic intermediate to the amine seems to be rate-limiting. A structure-activity study of 30 aniline derivatives that differ in hydrophobicity, position, size, charge, and number of substituents showed that some ortho-substituted derivatives were not acetylated.
Mol Pharmacol 1987 Apr
PMID:Purification, physicochemical, and kinetic properties of liver acetyl-CoA:arylamine N-acetyltransferase from rapid acetylator rabbits. 357 90

The effects of prostaglandins (PGs) on rat pineal metabolism were examined in vitro. PGE2 (0.01-1 microM) increased the activity of serotonin-N-acetyltransferase (SNAT), the stimulation curve exhibiting a maximum at 0.1 microM. PGE1 increased SNAT activity only at the highest dose (1 microM) whereas PGF2 alpha, 15-keto-PGF2 alpha or PGI2 did not affect the enzymic activity. The stimulation of SNAT activity brought about by PGE2 in pineals from ganglionectomized rats was greater than in sham-operated controls at all the doses studied, suggesting that the observed effect is predominantly post-synaptic. Only PGE2 significantly increased pineal cAMP accumulation in vitro at doses between 0.01 and 1 microM, and depressed the unoccupied cAMP-binding sites in pineal 900 g supernatants. The total number of cAMP-binding sites remained unaltered after incubation of PGE2. The present observations together with the previously reported NE-induced release of PGs in incubated pineal glands, the occurrence of pineal PG-binding sites and the indomethacin blockade of the nocturnal rise of pineal SNAT and melatonin content, support a role for PGs in the control of melatonin synthesis.
Mol Cell Endocrinol 1981 Aug
PMID:Prostaglandin E2 increases adenosine 3',5'-monophosphate concentration and binding-site occupancy, and stimulates serotonin-N-acetyltransferase activity in rat pineal glands in vitro. 626 70

Inhibition of pineal monoamine oxidase (MAO) activity either by harmine or pargyline in adult male Sprague-Dawley rats housed in a 12 : 12 LD cycle resulted in increase pineal N-acetyltransferase (NAT) activity. Pineal MAO inhibition also increased pineal melatonin content, presumably as a result of the increased NAT activity. Conjunct treatment with propranolol, a beta-adrenergic receptor antagonist, nullified these effects, regardless of the MAO inhibitor (harmine, pargyline or both) used or the inhibitor dose given. MAO inhibition during continuous light resulted in increased NAT activity greater than that observed following MAO inhibition during a 12 : 12 LD cycle. On the other hand, the increase in melatonin content following MAO inhibition during continuous light was not significantly different from that following MAO inhibition during a 12 : 12 LD cycle. Conjunct propranolol administration negated the effects of MAO inhibition on both the level of NAT activity and melatonin content, regardless of the lighting conditions. The level of pineal NAT activity is apparently regulated by the level of pineal beta-adrenergic receptor stimulation. While melatonin production appears to be dependent on increases in NAT activity, biosynthesis of this methoxyindole may also be regulated, in part, by other factors or processes in metabolic pathway.
Mol Cell Endocrinol 1982 Mar
PMID:Regulation of rat pineal melatonin synthesis: effect of monoamine oxidase inhibition. 627 62

An acetyltransferase from rat kidney microsomes that catalyzes the N-acetylation of thioethers of L-cysteine has been solubilized, stabilized, and separated from hydrolytic enzymes active against both the acetylated product, a mercapturic acid, and acetyl coenzyme A. Efficiency of catalysis varies with the lipophilicity of the substituent at sulfur in the order, ethyl less than propyl less than benzyl less than butyl, as predicted by the Hansch pi constants. Although L-tryptophan is acetylated at a very low rate, acetylation is not detectable for L-cysteine, L-methionine, L-serine, L-leucine, L-phenylalanine, or L-glutamic acid. The properties and substrate specificity reported here, along with previous studies on enzyme distribution, suggest that cysteine S-conjugate N-acetyltransferase is responsible for the final step in mercapturic acid biosynthesis.
Mol Pharmacol 1982 Mar
PMID:Cysteine S-conjugate N-acetyltransferase from rat kidney microsomes. 689 78

Kinetic parameters (ki and KI) were determined in vitro for the suicide inactivation of hamster hepatic N-arylhydroxamic acid N,O-acyltransferase by N-hydroxy-2-acetamidofluorene and N-hydroxy-4-acetamidobiphenyl. The inhibition of hamster hepatic N-arylhydroxamic acid N,O-acyltransferase by N-hydroxy-2-acetamidofluorene was not reversed by incubation with cysteine. Partial protection of the enzyme against inactivation was observed with low molecular weight nucleophiles (e.g., cysteine). Hamster hepatic CoASAc-dependent N-acetyltransferases were inactivated irreversibly by incubation with N-hydroxy-2-acetamidofluorene. p-Aminobenzoic acid CoASAc-dependent N-acetyl-transferase activity, but not sulfamethazine CoASAc-dependent N-acetyltransferase activity, was protected against inactivation when cysteine was included in the incubation mixtures. Therefore, although hamster hepatic CoASAc-dependent sulfamethazine N-acetyltransferase may be associated with N-arylhydroxamic acid N,O-acyltransferase, the CoASAc-dependent p-aminobenzoic acid N-acetyltransferase appears to be a different enzyme. The use of N-arylhydroxamic acids as suicide substrates is a promising technique for probing the mechanism of N-arylhydroxamic acid N,O-acyltransferase-mediated reactions, for exploring the relationships between N-arylhydroxamic acid N,O-acyltransferase and CoASAc-dependent N-acetyltransferases, and for selective inactivation in vitro of multiple forms of CoASAc-dependent N-acetyltransferases.
Mol Pharmacol 1982 Jan
PMID:Suicide inactivation of hamster hepatic arylhydroxamic acid N,O-acyltransferase. A selective probe of N-acetyltransferase multiplicity. 713 54

The activity and kinetics of N-acetyltransferase (NAT) in the quail duodenum were studied by radioenzymatic assay. NAT activity was highest when incubated under 37 degrees C, at pH 5.8 for 15 sec. Of the four substrates tested (tryptamine, 5,6-dihydroxytryptamine, serotonin, and N-acetylserotonin at concentrations of 0.08-4 mM), only tryptamine showed the substrate saturation phenomenon when incubated with the duodenal enzyme and acetyl-14C-coenzyme A. The saturation concentration of tryptamine was about 4 mM. Using the double reciprocal plot and regression equation, the Michaelis constant (Km) and maximal rate (Vmax) of NAT activity were found to be 0.204 mM and 0.917 nmol.mg protein-1.min-1, respectively. Diurnal study demonstrated higher NAT activity at middark (3.7 nmol.mg protein-1.min-1) and lower activity at midlight (2.4 nmol.mg protein-1.min-1), suggesting a circadian rhythm of the enzyme activities in the quail duodenum.
Comp Biochem Physiol B Biochem Mol Biol 1995 Oct
PMID:N-acetyltransferase activity in the quail (Coturnix coturnix jap) duodenum. 758 55


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