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61.
Lack of a Precursor-Product Relationship Between Histamine and Its Metabolites in Brain After Histidine Loading 总被引:1,自引:1,他引:0
George D. Prell Lindsay B. Hough Jai Khandelwal Jack Peter Green 《Journal of neurochemistry》1996,67(5):1938-1944
Abstract: Levels of histamine and its major metabolites in brain, tele -methylhistamine (t-MH) and tele -methylimidazoleacetic acid (t-MIAA), were measured in rat brains up to 12 h after intraperitoneal administration of l -histidine (His), the precursor of histamine. Compared with saline-treated controls, mean levels of histamine were elevated at 1 h (+ 102%) after a 500 mg/kg dose; levels of t-MH did not increase. Following a 1,000 mg/kg dose; levels mean histamine levels were increased for up to 7 h, peaked at 3 h, and returned to control levels within 12 h. In contrast, levels of t-MH showed a small increase only after 3 h; levels of t-MIAA remained unchanged after either dose. Failure of most newly formed histamine to undergo methylation, its major route of metabolism in brain, suggested that histamine was metabolized by another mechanism possibly following nonspecific decarboxylation. To test this hypothesis, other rats were injected with α-fluoromethylhistidine (α-FMHis; 75 mg/kg, i.p.), an irreversible inhibitor of specific histidine decarboxylase. Six hours after rats received α-FMHis, the mean brain histamine level was reduced 30% compared with saline-treated controls. Rats given His (1,000 mg/kg) 3 h after α-FMHis (75 mg/kg) and examined 3 h later had a higher (+112%) mean level of histamine than rats given α-FMHis, followed by saline. Levels of t-MH and t-MIAA did not increase. These results imply that high doses of His distort the simple precursor-product relationship between histamine and its methylated metabolites in brain. The possibility that some His may undergo nonspecific decarboxylation in brain after His loading is discussed. These findings, and other actions of His independent of histamine, raise questions about the validity of using His loading as a specific probe of brain histaminergic function. 相似文献
62.
Properties and chemical modification of D-amino acid oxidase from Trigonopsis variabilis 总被引:2,自引:0,他引:2
The basic properties of purified d-amino acid oxidase from the yeast Trigonopsis variabilis were investigated. The pH optimum of activity was between pH 8.5 and 9.0, and the native molecular masses of holo- and apo-enzyme
were determined to be 170 kDa; higher aggregates corresponded to molecular masses of 320 and 570 kDa. The apparent V
max and K
m values for different substrates varied between 3.7 to 185 U/mg and 0.2 to 17.3 mM, respectively. The reaction of d-amino acid oxidase with sulfite was followed by the typical spectral modifications of the FAD resembling the reduced enzyme;
a K
d of 30 μM was calculated for the N(5)-adduct. The red anionic flavin radical of the enzyme was stable; benzoate had no influence
on the spectral properties. A complete loss of enzyme activity was observed after chemical modification by the histidine-specific
reagent diethyl pyrocarbonate. The inactivation showed pseudo-first-order kinetics, with a second-order rate constant of 13.6
M–1 min–1 at pH 6.0 and 20°C. The addition of a substrate under anoxic conditions led to a substantial protection from inactivation,
which indicates a localization of the modified residues close to the active site. The pKa of the reacting group was determined to be 7.7, and the rate of inactivation reached a limiting value of 0.031 min–1.
Received: 22 August 1995 / Accepted: 17 October 1995 相似文献
63.
Summary
S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]-3-mercaptopyruvic acid (I) was chemically synthesized in 15% yield by incubating a reaction mixture oftrans-urocanic acid and 3-fold excess of 3-mercaptopyruvic acid at 45°C for 6 days. The synthesized compound was characterized by fast-atom-bombardment mass spectrometry and high-voltage paper electrophoresis. CompoundI was identified with a product of an enzymatic reaction ofS-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-l-cysteine (II) with rat liver homogenate in a phosphate buffer, pH 7.4. CompoundI was degraded toS-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-3-mercaptolactic acid (III), a compound previously found in human urine [Kinuta et al. (1994) Biochem J 297: 475–478], by incubation with rat liver homogenate. From these results, we suggest that compoundI is a metabolic intermediate for the formation of compoundIII from compoundII. The present pathway follows a formation of compoundII fromS-[2-carboxy-1-(1H-imidazol-4-yl)ethyl] gluthathione [Kinuta et al. (1993) Biochim Biophys Acta 1157: 192–198], a proposed metabolite ofl-histidine. 相似文献
64.
65.
通过酒精提取、丙酮浓缩,从天然带毒的赤霉病元麦中制备粗毒素。化学分析表明既含脱氧雪腐镰刀菌烯醇,又含玉米赤霉烯酮。以此粗毒素0,125,250,500,1,000mg/kg体重于孕期7—16天连续灌胃授予Wlstar妊娠大鼠。结果发现:1,000mg/kg有明显的胚胎毒作用;250rag/kg以上有胎儿毒作用和致畸作用。另以不同浓度的粗毒素柱层析纯化物和脱氧雪腐镰刀菌烯醇纯品测试了对鼠伤寒沙门氏菌组氨酸缺陷型菌株的致突变性。结果表明:加与不加S-9混合液均有诱变性,但存在着一定的剂量-反应差异。 相似文献
66.
Inhibition of Histamine Synthesis in Brain by α-Fluoromethylhistidine, a New Irreversible Inhibitor: In Vitro and In Vivo Studies 总被引:2,自引:2,他引:0
a-Fluoromethylhistidine (α-FMH), a new potent inhibitor of histidine decarboxylase (HD), has been used for in vitro and in vivo studies of brain HD. Following a preincubation with (+)-α-FMH, brain HD activity was inhibited in a time-dependent and concentration-dependent manner. The enzyme activity was not restored by overnight dialysis against standard buffer. The (–) antimer of α-FMH was ineffective. When injected intraperitoneally in a single dose of 20 mg/kg, (±)-α-FMH induced a complete loss in HD activity in cerebral cortex and hypothalamus as well as in peripheral tissues, such as stomach. At a dosage of 100 mg/kg (±)-α-FMH did not alter histamine-N-methyltransferase, DOPA decarboxylase, and glutamate decarboxylase activities. The maximal decrease of HD activity occurred after 2 h in both cerebral cortex and hypothalamus, but the time course of the recovery of enzyme activity was slower in the cerebral cortex. The enzyme activity reached control value within 3 days in hypothalamus and was not fully restored after 4 days in cerebral cortex. Contrasting with the diminished HD activity, a substantial concentration of histamine remained present in five regions of mouse brain. Thus, α-FMH is a highly specific irreversible inhibitor of brain HD activity and its efficacy makes it useful to study the physiological role of brain histamine. 相似文献
67.
Hydrogen peroxide (H2O2) can diffuse far from the site of production to intracellular locations where biological effects may be greater. The diffusion range is extended by H2O2 carriers formed spontaneously by hydrogen bonding with monomeric and polymeric compounds, including amino and dicarboxylic acids, peptides, proteins, nucleic acid bases, and nucleosides. Hydrogen peroxide adducts (HPAs) are readily synthesized, e.g., crystalline histidine (His)-H2O2 adducts. An equilibrium exists between an adduct-forming compound and H2O2. The detection and relative stabilities of HPAs are measured by the degree of decomposition of H2O2 as influenced by test compounds in buffered solution competing with glucose or fructose for H2O2. The HPAs delay decomposition of H2O2 up to several hundredfold. The overall charge on an HPA, i.e., its ability to penetrate cell membranes, influences the cytotoxic and clastogenic effects of H2O2. Growth inhibition of Salmonella typhimurium LT2 by H2O2 is enhanced by neutral HPAs but decreased by anionic HPAs. Addition of catalase 1, 10, or 30 min after inoculation of S. typhimurium LT2 reduces or nearly eliminates partial growth inhibition by H2O2, but a neutral HPA, expecially his-H2O2, transported H2O2 into the cells within 1 min, and in about 10 min completely inhibited growth. The stability of HPAs decreases with increasing pH or increasing temperature, while added Fe(II) in the presence and absence of EDTA accelerates H2O2 and HPA decomposition. Calculations indicate H2O2 hydrogen bonds with nucleic acid-base pairs with no apparent bond strain and energy stabilization comparable to normal hydrogen bonding. 相似文献
68.
A new form of L-histidine L-aspartate monohydrate crystallizes in space group P22 witha = 5.131(1),b = 6.881(1),c= 18.277(2) Å,β= 97.26(1)° and Z = 2. The structure has been solved by the direct methods and refined to anR value of 0.044 for 1377 observed reflections. Both the amino acid molecules in the complex assume the energetically least favourable allowed conformation with the side chains staggered between the α-amino and α-scarboxylate groups. This results in characteristic distortions in some bond angles. The unlike molecules aggregate into alternating double layers with water molecules sandwiched between the two layers in the aspartate double layer. The molecules in each layer are arranged in a head-to-tail fashion. The aggregation pattern in the complex is fundamentally similar to that in other binary complexes involving commonly occurring L amino acids, although the molecules aggregate into single layers in them. The distribution of crystallographic (and local) symmetry elements in the old form of the complex is very different from that in the new form. So is the conformation of half the histidine molecules. Yet, the basic features of molecular aggregation, particularly the nature and the orientation of head-to-tail sequences, remain the same in both the forms. This supports the thesis that the characteristic aggregation patterns observed in crystal structures represent an intrinsic property of amino acid aggregation. 相似文献
69.
Naohiro Tateda Kiichi Matsuhisa Kiyoshi Hasebe Nagomi Kitajima Toshiaki Miura 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1998,718(2):968
A high-performance liquid chromatographic method was developed for the rapid and sensitive determination of histidine. The method is based on separation by reversed-phase ion-pair chromatography followed by highly selective fluorescence derivatization of histidine with o-phthaldialdehyde. A linear calibration curve was obtained over the range of 0.25–200 pmol per injection (10 μl) with the coefficient of variation of 0.9% at 2 pmol (n=10) and with the detection limit (S/N=8) of 25 fmol. The method was applicable to the assay of histidine in human serum. Serum histidine values obtained by the present method were in good agreement with values obtained with an amino acid analyzer. 相似文献
70.
Identification of Azospirillum strains by restriction fragment length polymorphism of the 16S rDNA and of the histidine operon 总被引:3,自引:0,他引:3
Annamaria Grifoni Marco Bazzicalupo Claudia Di Serio Silvia Fancelli renato Fani 《FEMS microbiology letters》1995,127(1-2):85-91
Abstract DNA fingerprints of several Azospirillum strains, belonging to the five known species A. amazonense, A. brasilense, A. halopraeferens, A. irakense and A. lipoferum , were obtained by restriction analysis of the amplified 16S rDNA and by restriction fragment length polymorphism of the histidine biosynthetic genes. Data obtained showed that amplified rDNA restriction analysis is an easy, fast, reproducible and reliable tool for identification of Azospirillum strains, mainly at the species level, whereas restriction fragment length polymorphism could, in some cases, differentiate strains belonging to the same species. Moreover, both analyses gave congruent results in grouping strains and in the assignment of new strains to a given species. 相似文献