Drug-induced teratogenesis in vitro: inhibition of calcification by different tetracyclines

Inhibition of calcification in embryonic bone rudiments was studied in the presence of several tetracyclines at three different concentrations. Different criteria for calcification and different concentrations of tetracyclines yielded parallel results and showed significant differences in the inhibitory action of the various compounds. The clear-cut results indicate that the test-system that was developed may be useful for the comparison of various teratogens under simplified controllable conditions.     

Protein digestion in isolated lysosomes inhibited by intralysosomal trypan blue

Control rats and rats treated with subcutaneous trypan blue were injected intravenously with denatured albumin-I(125). Lysosome-rich fractions of their livers, when incubated at 22 degrees C in osmotically protected medium (pH 7.4), retained their capacit to digest albumin-I(125). The rate of digestion was lower in suspensions pre-pared from rats treated with trypan blue than in control suspensions, but rates of lysosome breakage were not different. T'hese results and other experimental evidence suggest that trypanblue concentrated within lysosomes can inhibit intralysosomal digestion, probably by inhibition of lysosomal proteinases.     

Mechanism of enzyme inhibition by phosphate esters

A theory for the rapid specific reaction of certain phosphorous-containing esters with many proteolytic enzymes based on the ability of phosphorous to form one additional bond relative to carbon is presented. A stable tetrahedral phosphate ester is compared with a labile tetrahedral orthocarbonyl ester and a relatively stable pentagonal enzyme-phosphate ester complex is compared with a pentagonal enzyme-carbonyl substrate complex. The latter complex is assumed to be the transition state in the enzyme-catalyzed reaction. If the theory is correct, it opens up the possibility of studying intermediates and transition states from the known structures of chemical inhibitors.     

酶抑制法测定有机磷农药含量

通过测定乙酸-1-萘酯在酯酶(蚕蛹酶、鸡肝酶和面粉酶)催化下水解生成的乙酸被有机磷农药抑制前后pH值的变化,推算出有机磷农药对酯酶的抑制率,从而检测出有机磷农药的含量.以ΔpH值为指标,经由单因素试验得出最佳酶促反应条件:反应时间30 min、反应温度35 ℃、固蓝B盐1 mL、乙酸-1-萘酯3 mL.结果发现蚕蛹酶活性最高,且农药对酶的抑制具有选择性,混合酶液未出现特异性提高.     

Chemical aspects of enzyme inhibition

The use of chemical reagents as enzyme inhibitors has yielded information concerning the mechanism of inhibition and the role in catalysis played by active groups on the protein apoenzyme, the coenzyme, or the metal component. Inhibition analysis has also furnished valuable clues concerning the architecture, chemical properties, and catalytic mechanism of the active site of the enzyme. In many cases, in vivo effects of inhibitors can be closely correlated with in vitro inhibition of purified enzyme systems. The effects of antimicrobial and anticancer agents, insecticides, and drugs can often be explained in terms of enzyme inhibition. The design and synthesis of new inhibitors offers great promise when applied to the control of undesirable organisms and to the prevention and cure of disease in the immediate future.     

Feedback inhibition of glycerol kinase, a catabolic enzyme in Escherichia coli

Fructose-1 ,6-diphosphate is a feedback inhibitor of the catabolic enzyme, glycerol kinase, in Escherichia coli. A mutant was isolated which produced a desensitized enzyme. Glucose was no longer as effective in preventing the utilization of exogenous glycerol by cells which synthesized constitutively such an altered enzyme, even though the usual degree of catabolite repression still operated.     

Maya blue: a clay-organic pigment?

Maya Blue, a pigment used by the Mayas in Yucatan, is remarkably stable: the color is not destroyed by hot concentrated mineral acids or by heating to about 250 degrees C. The principal constituent is the colorless mineral attapulgite. It is proposed that the pigment is an adsorption complex of attapulgite and natural indigo; a synthetic equivalent may be prepared from attapulgite and either indoxylester or indigo, or by applying the vat-dyeing technique, with reduced indigo.The low dye content of the pigment (less than 0.5 percent) indicates that the dye is absorbed only on the external surfaces of the attapulgite particles and not throughout the channels in their structures. The complex as such is not stable to acids, but the stability displayed by Maya Blue is achieved simply by heating the complex to from 75 degrees to 150 degrees C for several days. An analogous stable pigment can be prepared from sepiolite and indigo. No stable pigments could be prepared from clays with platelike structures or from zeolites.     

普鲁士蓝对养殖液中亚甲基蓝的光热催化降解

【目的】探究亚微米普鲁士蓝(Submicron Prussian blue,smPB)的光热转化效果对其光芬顿催化降解亚甲基蓝(Methylene blue, MB)污染物的促进作用。【方法】以亚铁氰化钠和聚乙烯亚胺为主要材料,在酸性条件下,通过水热缓慢结晶法,利用聚乙烯亚胺链上的氨基基团控制普鲁士蓝(Prussian blue, PB)的结晶过程,制备出具有光热及光芬顿催化降解能力的smPB。使用扫描电子显微镜(SEM)、紫外-可见漫反射吸收光谱(UV-Vis)、透射电子显微镜(TEM)、傅里叶红外分光光度计(FTIR)、X射线衍射仪(XRD)等测试仪器对smPB进行结构和形貌表征。利用太阳光模拟器照射的阳光测试了smPB在水溶液中的光热转化效果。在不同的催化条件下,测试了smPB的芬顿、光芬顿以及光热芬顿催化降解效率。【结果】smPB的光热转化率约为90%。太阳光模拟器以1个太阳光功率照射1 h的情况下,含有smPB 20 mg的100 mL水溶液温度上升8.8℃左右。在光热的条件下,使用20 mg的smPB对100 mL的MB溶液(ρ=20 mg/L)进行光热芬顿催化降解,在40...     

Adenovirus multiplication: inhibition by methisazone

Methisazone (5 to 40 microM) inhibited the multiplication of types 3, 7, 9, 11, 14, 16, 17, 21, and 28 adenovirus; SV15 (a simian adenovirus) was also inhibited. A study of adenovirus 11 under single-cycle conditions showed that multiplication of the virus, was completely inhibited by 30 microM methisazone when addition of the compound was delayed until 13 hours after infection. A survey showed that the structure-activity relations of the action of methisazone against adenoviruses and pox viruses are similar.     

Triggering of allostery in an enzyme by a point mutation: ornithine transcarbamoylase

The origin of allostery is an unanswered question in the evolution of complex regulatory proteins. Anabolic ornithine transcarbamoylase, a trimer of identical subunits, is not an allosteric enzyme per se. However, when the active-site residue arginine-106 of the Escherichia coli enzyme is replaced with a glycine through site-directed mutagenesis, the resultant mutant enzyme manifests substrate cooperativity that is absent in the wild-type enzyme. Both homotropic and heterotropic interactions occur in the mutant enzyme. The initial velocity saturation curves of the substrates, carbamoyl phosphate and L-ornithine, conform to the Hill equation. The observed cooperativity depends on substrate but not enzyme concentration. The finding underscores the possibility that a single mutation of the enzyme in the cell could turn transcarbamoylation into a regulatory junction in the biosynthesis of L-arginine and urea.     

Chloroplast ribosomes: stereospecificity of inhibition by chloramphenicol

Chloroplast ribosomes from tobacco leaves show the same stereospecificity of inhibition by chloramphenicol as bacterial ribosomes do. Cytoplasmic ribosomes from the same leaves are unaffected by chloramphenicol. These results remove doubts raised by nonstereospecific effects of chloramphenicol on higher plant cells and support the concept that chloroplasts have evolved from prokaryotes.     

Desmosine biosynthesis: nature of inhibition by D-penicillamine

Administration of D-penicillamine and lathyrogens such as beta-amino-propionitrile to animals markedly alters connective tissue by preventing the normal cross-linkage of elastin and collagen. It had been shown that beta-aminopropionitrile blocks the cross-linkage of elastin and collagen by preventing the initial step in cross-linkage: the conversion of lysine in peptide linkage to alpha-amino adipic-delta-semialdehyde. We show that penicillamine acts after the initial step, causing the accumulation of an elastin rich in alpha-amino adipic-delta-semialdehyde.     

Neuromuscular transmission: inhibition by manganese ions

Manzganiese ions. are potent blocking argenits of synaptic transmission at the neuromuscular junction in the frog. The main site of action is the presynaptic nerve terminal, where the ions decr-ease the amount of transmitter liberated by a never impulse. The inihibition produced by manganese is reversible.     

Chondroitin sulfate: inhibition of synthesis by puromycin

Puromycin reversibly inhibits synthesis of chondroitin sulfate by vertebral chondrocytes from 10-day-old chick embryos. Treatment of these cells with puromycin for 5 hours does not affect viability or capacity to multiply on subsequent release from their matrix. It is suggested that synthesis of this polysaccharide is coupled with that of protein; there may be a feedback control in its synthesis.     

Electric fields at the active site of an enzyme: direct comparison of experiment with theory

The electric fields produced in folded proteins influence nearly every aspect of protein function. We present a vibrational spectroscopy technique that measures changes in electric field at a specific site of a protein as shifts in frequency (Stark shifts) of a calibrated nitrile vibration. A nitrile-containing inhibitor is used to deliver a unique probe vibration to the active site of human aldose reductase, and the response of the nitrile stretch frequency is measured for a series of mutations in the enzyme active site. These shifts yield quantitative information on electric fields that can be directly compared with electrostatics calculations. We show that extensive molecular dynamics simulations and ensemble averaging are required to reproduce the observed changes in field.     

酶抑制法两种底物优越性比较试验

酶抑制法是根据农药对酯酶的抑制率与样品中有机磷农药浓度的对数成正比关系,来定量分析有机磷农药残留量。酶抑制法常用的底物有2,6-二氯靛酚乙酸酯和固兰B盐,通过对这两种底物的优越性进行比较试验,结果表明:2,6-二氯靛酚乙酸酯较固兰B盐更优越,更适合于有机磷农药的快速现场检测。2,6-二氯靛酚乙酸酯作为底物的优越性主要表现在:与生成物有良好的稳定性;植物酯酶的反应条件较为协调合理;敌敌畏对植物酯酶的抑制率与农药浓度对数值呈良好的线性关系;用添加农药法测定的回收率较高。