Abstract:
:In the present study, a screen of adenosine analogs as potential modulators of arylamine-N-acetyltransferase 1 activity identified ATP as an inhibitor within its range of physiological concentrations. Kinetically, ATP was a non-competitive inhibitor with respect to the acetyl acceptor but a competitive inhibitor with respect to the acetyl donor (acetyl-coenzyme A). In silico modelling predicted that ATP bound within the active site cleft arranged with the triphosphate group in close proximity to arginine 127. Since lysine 100 has previously been implicated in the binding of acetyl-coenzyme A to the enzyme, this amino acid was mutated to either an arginine or a glutamine. Both substitutions significantly changed the affinity of ATP for the enzyme, as well as the nature of the interaction to one with a large Hill coefficient (>3). Under these conditions, ATP was a strong allosteric modulator of arylamine-N-acetyltransferase 1 activity. Western blot analysis identified lysine 100 as a site of post-translational modification by acetylation. The results suggest that acetylation of lysine 100 converts arylamine-N-acetyltransferase 1 into a switch modulated by ATP. This observation provides important understanding of the molecular regulation of NAT1 activity and may reveal possible insight into the endogenous role of the enzyme.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Minchin RF,Rosengren KJ,Burow R,Butcher NJdoi
10.1016/j.bcp.2018.10.013subject
Has Abstractpub_date
2018-12-01 00:00:00pages
153-160eissn
0006-2952issn
1873-2968pii
S0006-2952(18)30434-9journal_volume
158pub_type
杂志文章abstract::The in-vivo effect of dehydroepiandrosterone (DHEA) on hepatic enzyme activities of rats, mice, hamsters and guinea pigs was investigated. After DHEA treatment (300 mg/kg body weight, per os, 14 days), the activities of peroxisomal beta-oxidation, catalase, carnitine acetyltransferase, carnitine palmitoyltransferase, ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90502-a
更新日期:1992-03-17 00:00:00
abstract::An imbalance of T helper cell type 1 (Th1) versus type 2 (Th2) polarization in favor of Th1 cell subsets appears to be a key pathogenic mechanism in chronic inflammatory bowel disease (IBD), in particular in Crohn's disease. The interferon gamma-inducing factor interleukin (IL)-18 acts in strong synergism with the Th1...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(02)01064-x
更新日期:2002-07-01 00:00:00
abstract::The effect of natural polyphenols on three isoforms of NO-synthase was investigated. Among the compounds tested, tannin was the most potent, inhibiting endothelial constitutive NO synthase (eNOS) with an IC50 of 2.2 microM. Other NOS isoforms (i.e. neuronal constitutive NOS and smooth muscle inducible NOS) were also i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)00433-m
更新日期:1995-02-14 00:00:00
abstract::The treatment of rats with 10 mumoles/kg (s.c.) of mercuric chloride (Hg2+) caused time-dependent decreases in the activities of the enzymes of the glutathione (GSH) metabolism pathway in the kidney. Twenty-four hours after administration of Hg2+, the activities of gamma-glutamylcysteine synthetase and glutathione dis...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90085-5
更新日期:1982-10-01 00:00:00
abstract::[Carboxyl-14C] labelled 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (I) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (II) were synthesized and their decarboxylation was studied in mouse brain homogenate and buffer. The decarboxylation rates of (I) and (II) in the homogenate were about 6-fol...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90173-5
更新日期:1986-08-15 00:00:00
abstract::Breast cancer is the most prevalent type of tumor and the second leading cause of death due to cancer among women. Although screening methods, diagnosis and therapeutic options have improved in the last decade, chemoresistance remains an important challenge. There is evidence relating breast cancer resistance with sig...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.113959
更新日期:2020-07-01 00:00:00
abstract::Structurally diverse chemotherapeutic and chemopreventive drugs, including camptothecin, doxorubicin, sanguinarine, and others, were found to cause covalent crosslinking of proliferating cell nuclear antigen (PCNA) trimers in mammalian cells exposed to fluorescent light. This PCNA damage was caused by both nuclear and...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.09.003
更新日期:2008-12-15 00:00:00
abstract::Novel hydroxynaphthoquinones have been shown to be potent and selective inhibitors of mitochondrial electron transport in the protozoan Eimeria tenella, inhibiting at concentrations of 10(-10) to 10(-11)M. The primary site of electron transport inhibition has been localized to the ubiquinol-cytochrome c reductase span...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90581-1
更新日期:1984-07-01 00:00:00
abstract::The formyl peptide receptor (FPR) gene family has a complex evolutionary history and comprises eight murine members but only three human representatives. To enable translation of results obtained in mouse models of human diseases, more comprehensive knowledge of the pharmacological similarities/differences between the...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.09.004
更新日期:2016-11-01 00:00:00
abstract::During tumor progression, hypoxia-inducible factor 1 (HIF-1) plays a critical role in tumor angiogenesis and tumor growth by regulating the transcription of several genes in response to a hypoxic environment and changes in growth factors. This study was designed to investigate the effects of cinnamic aldehyde (CA) on ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.08.095
更新日期:2015-11-01 00:00:00
abstract::The recognition sites for the 5-hydroxytryptamine (5-HT) uptake inhibitors imipramine and paroxetine may represent receptors for a presently unknown endogenous ligand, whose function would be to modulate 5-HT uptake. Attempts to isolate such a factor from rat brain tissue are described, following a published procedure...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90189-4
更新日期:1987-03-15 00:00:00
abstract::Cyclic guanosine 3'-5'-monophosphate (cGMP) has recently been shown to constitute a second messenger for Xenopus laevis melatonin Mel1c receptors. To verify whether cGMP levels are also modulated by mammalian melatonin receptors, we cloned the genes encoding the human Mel1a and Mel1b receptor subtypes and expressed th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00134-3
更新日期:1999-08-15 00:00:00
abstract::This study was designed to examine the relationship between the extent of Sandimmun (cyclosporin A, SIM) metabolism and SIM-induced hepatotoxicity both in vivo and in primary cultures of rat hepatocytes. Firstly, SIM (50 mg/kg p.o.) was administered daily to male Wistar rats for 10 days with or without co-administrati...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90024-f
更新日期:1990-01-15 00:00:00
abstract::Antagonists of the chemokine receptor, CCR5, may provide important new drugs for the treatment of HIV-1. In this study we have examined the mechanism of action of two functional antagonists of the chemokine receptor CCR5 (UK-396,794, UK-438,235) in signalling and internalisation assays using CHO cells expressing CCR5....
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.06.032
更新日期:2007-09-15 00:00:00
abstract::LCY-2-CHO has anti-inflammatory actions on macrophages. To understand its therapeutic implication in atherosclerosis, we examined its effects on the expressions of anti-inflammatory and inflammatory proteins in cultured rat aortic vascular smooth muscle cells (VSMC). LCY-2-CHO is able to induce heme oxygenase-1 (HO-1)...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.04.008
更新日期:2007-07-15 00:00:00
abstract::Since neurotensin is often co-stored with catecholamines and since it can excite the release of dopamine and norepinephrine, responses to this peptide might depend upon the activity of catecholaminergic systems. In this study, we used prostate cancer PC3 cells, which express neurotensin receptors and 12-adrenergic rec...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00064-7
更新日期:1999-06-15 00:00:00
abstract::The proinflammatory cytokine interleukin (IL)-18 appears to be involved in the pathogenesis of diseases associated with immunoactivation and inflammation. Consequently, blockage of IL-18 bioactivity by use of IL-18 binding protein (IL-18 BP) is likely a promising therapeutic concept. In the present study, we investiga...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00294-6
更新日期:2003-08-01 00:00:00
abstract::Exposure to ultraviolet B (UVB) irradiation induces acute skin inflammation such as erythema (sunburn) and edema, and prostaglandin (PG)E2 in the epidermis plays an important role as its prominent mediator. In the present study, we investigated the effect of nobiletin (5,6,7,8,3',4'-hexamethoxy flavone) from Citrus de...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.04.006
更新日期:2004-08-01 00:00:00
abstract::Inflammation is a multi-staged process whose expansive phase is thought to be driven by acutely released arachidonic acid (AA) and its metabolites. Inhibition of cyclooxygenase (COX), lipoxygenase (LOX), or soluble epoxide hydrolase (sEH) is known to be anti-inflammatory. Inhibition of sEH stabilizes the cytochrome P4...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.10.025
更新日期:2010-03-15 00:00:00
abstract::Calmodulin can be specifically acylated with a fluorene-containing hydrophobic spin-labeling reagent at just Lys 75 or at Lys 75 and Lys 148. The binding of trifluoperazine to calmodulin and the two adducts was determined using a Hummel-Dreyer procedure, and binding of the phenothiazine was found to be characterized b...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90754-9
更新日期:1986-12-15 00:00:00
abstract::The biotransformation and the hepato- and nephrotoxicity of the mercapturic acids (N-acetyl-1-cysteine S-conjugates) of three structurally related 2,2-difluoroethylenes were investigated in vivo in the rat. All mercapturic acids appeared to cause nephrotoxicity, without any measureable effect on the liver. The mercapt...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90665-x
更新日期:1988-12-01 00:00:00
abstract::The effect of low M(r) heparin fragments (CY222) and fetal calf serum (FCS) on the level of fibronectin and fibrillar collagen mRNAs was investigated in smooth muscle cells (SMC) in culture. In the absence of FCS, addition of CY222 (100 micrograms/10(6) cells) to postconfluent early passage SMC resulted in a decrease ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)00462-u
更新日期:1995-03-01 00:00:00
abstract::The anti-peroxidative activity of eugenol on Fe(2+)-ascorbate- and Fe(2+)-H2O2-induced lipid peroxidation was studied using rat liver mitochondria. Eugenol inhibited thiobarbituric acid reactive substance (TBARS) formation induced by both the systems in addition to oxygen uptake and mitochondrial swelling induced by F...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90318-d
更新日期:1992-06-09 00:00:00
abstract::Cilostamide derivatives are potent inhibitors of human platelet aggregation and selectively inhibit human platelet cyclic adenosine monophosphate (cyclic AMP) phosphodiesterase. N-Cyclohexyl-N-(2-hydroxybutyl)-5-[6-1,2,3,4-tetrahydro-2-oxoquinolyl oxy)] -butyramide (OPC-13135) is one of these derivatives, and the conc...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90103-5
更新日期:1984-11-01 00:00:00
abstract::The cysteine (Cys) precursor 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA) has been shown to protect against acetaminophen (APAP)-induced hepatic GSH, GSSG, and Cys depletion and hepatic necrosis. The aim of this study was to determine the effects of PTCA on the concentrations of sulfhydryl compounds in extra...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00539-1
更新日期:2001-04-01 00:00:00
abstract:BACKGROUND:Flavonoids form a diverse class of naturally occurring polyphenols ascribed various biological activities, including inhibition of amyloid β (Aβ) fibrillisation and neurotoxicity of relevance to Alzheimer's disease. Cannabis contains a unique subset of prenylated flavonoids, the cannflavins. While selected c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.08.011
更新日期:2019-11-01 00:00:00
abstract::The carrier protein for methotrexate and tetrahydrofolate cofactors (GP-MTX) in CCRF-CEM human lymphoblastic leukemia cells in a 117 kDa glycoprotein containing both N- and O-linked oligosaccharides (Matherly et al., J Biol Chem 267: 23253-23260, 1992). Tunicamycin, an inhibitor of N-glycosylation, was used to investi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90423-5
更新日期:1994-03-15 00:00:00
abstract::The cellular distribution of cytochrome P-450 has been studied in the liver and a number of extrahepatic tissues in the rat by immunocytochemistry, using an antibody raised against cytochrome P-450 form c. Immunoreactive cytochrome P-450, most probably form c, was found in the proximal tubules of the kidney, in the Cl...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90777-x
更新日期:1986-12-15 00:00:00
abstract::Tumor necrosis factor (TNF) is a pleiotropic cytokine that mediates different cellular responses including cytotoxicity, cytostasis, proliferation, differentiation and expression of specific genes. Recent studies have demonstrated that chemotherapeutic drugs that inhibit the nuclear enzyme DNA topoisomerase II synergi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90468-c
更新日期:1993-10-05 00:00:00
abstract::After partial hepatectomy (PHx), there are significant changes in the activity of a number of enzymes in the regenerating rat liver. Administration of low doses of recombinant human tumor necrosis factor-alpha (rHu-TNF) to normal rats induces similar changes in some of the enzymes but not in others. Because certain ob...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00265-2
更新日期:1995-10-12 00:00:00