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1.
A small library of (E) α,β-unsaturated fatty acids was prepared, and 20 different saturated and mono-unsaturated fatty acids differing in chain length were subjected to Ellman’s assays to determine their ability to act as inhibitors for AChE or BChE. While the compounds were only very weak inhibitors of BChE, seven molecules were inhibitors of AChE holding IC50?=?4.3–12.8?M with three of them as significant inhibitors of this enzyme. The results have shown trans 2-mono-unsaturated fatty acids are better inhibitors for AChE than their saturated analogs. Furthermore, the screening results indicate that the chain length is crucial for obtaining an inhibitory efficacy. The best results were obtained for (2E) eicosenoic acid (14) showing inhibition constants Ki?=?1.51?±?0.09?M and Ki′?=?7.15?±?0.55?M. All tested compounds were mixed-type inhibitors with a dominating competitive part. Molecular modelling calculations indicate a different binding mode of active/inactive compounds for the enzymes AChE and BChE.  相似文献   

2.
《Phytochemistry》1987,26(5):1299-1300
The effect ofpH on Km and Vmax values of coconut α-galactosidase indicates the involvement of two ionizing groups with pKa values of 3.5 and 6.5 in catalysis. Chemical modification has indicated the presence of two carboxyl groups, a tryptophan and a tyrosine, at or near the active site of α-galactosidase. Based on these facts a new mechanism of action for α-galactosidase is proposed in which the ionizing group with a pKa of 3.5 is a carboxyl group involved in stabilizing a carbonium ion intermediate and the ionizing group with a pKa of 6.5 is a carboxyl group perturbed due to the presence of a hydrophobic residues in its vicinity which donates a H+ ion in catalysis.  相似文献   

3.
The KI values for inhibition of thermolysin activity by N-β-phenylpropionyl-aliphatic amino acids (Gly, Ala, Val, Leu, Ile) are correlated by π, the hydrophobic substituent parameter for the amino acid side chain (log KI = ?0.73π ?1.80, correlation coefficient = 0.990). By contrast, the KI values for the corresponding benzyloxycarbonyl amino acids are poorly correlated by π, but show a good correlation with the steric parameter Es(log KI = 0.880Es ? 3.086, correlation coefficient = 0.985). Binding of β-phenylpropionyl-l-alanine is associated with an acidic residue of pK 7.3 and a basic residue of pK 8.0 in the E · I complex, and appears to raise the pK of Glu-143 by 2 units. Binding of benzyloxycarbonyl-Ala and -Phe is associated with an acidic residue of pK 8.0 and two basic residues, both with pK 8.3. Three similar pK values are observed with benzyloxycarbonyl-Phe. These results are interpreted in terms of different modes of binding of β-phenylpropionyl and benzyloxycarbonyl inhibitors.  相似文献   

4.
S-Adenosylhomocysteine (SAH), a potent inhibitor of methyltransferases, and several thioethers structurally related to SAH, have been tested as potential inhibitors of tRNA (guanine-7)-methyltransferase from Salmonella typhimurium. The tested compounds are l-, d-, dl-S-adenosylhomocysteine, S-adenosylcysteine, methylthioadenosine, butylthioadenosine, thioethanoladenosine, isobutylthioadenosine, S-inosylhomocysteine, and methylthioinosine. Among them the highest inhibitory activity has been shown by SAH (Ki = 8 μM), whereas butylthioadenosine, isobutylthioadenosine, and thioethanoladenosine are almost inactive as inhibitors. The other compounds inhibit the enzyme with Ki values ranging between 400 and 800 μm. From these data it is possible to evaluate the importance of the -NH2 and -COOH groups of the substrate in the binding to the enzyme molecule, as well as other features such as the chirality at the α-carbon atom and the length of the hydrocarbon chain connecting the -NH2 and -COOH groups to the aromatic ring of adenosine. The aminic group of the adenosine is also critical, because S-inosylhornocysteine and methylthioinosine are poorer inhibitors in comparison with SAH and methylthioadenosine.  相似文献   

5.
Twenty-five analogs of d-glucose were examined as reversible inhibitors of yeast α-glucosidase (EC 3.2.1.20). The Ki values range from 0.38 mM for 6-deoxy-d-glucose (quinovose) to 1.0 M for d-lyxose at pH=6.3 (0.1 M NaCl, 25°). All the monosaccharides and the three disaccharides (maltose, isomaltose and α,α-trehalose) were found to be linear competitive inhibitors with respect to α-p-nitrophenyl glucoside (pNPG) hydrolysis. Multiple inhibition analysis reveals that there are at least three monosaccharide binding sites on the enzyme. One of these can be occupied by glucose [Ki=1.8(±0.1) mM], one by d-galactose [Ki=164(±11) mM] and one by d-mannose [Ki=120(±9) mM]. The pH dependence for glucose binding closely follows that of V/K [pKa1=5.55(±0.15), pKa2=6.79(±0.15)], but the binding of mannose does not. Although the glucose subsite can be occupied simultaneously with the mannose or galactose subsites in the enzyme–product complex, no transglucosylation can be detected between pNPG and either mannose or galactose. This suggests that neither of these nonglucose subsites can be occupied in a productive manner in the covalent glucosyl-enzyme intermediate.  相似文献   

6.
The β-subunit of the voltage-sensitive K+ channels shares 15–30% amino acid identity with the sequences of aldo–keto reductases (AKR) genes. However, the AKR properties of the protein remain unknown. To begin to understand its oxidoreductase properties, we examine the pyridine coenzyme binding activity of the protein in vitro. The cDNA of Kvβ2.1 from rat brain was subcloned into a prokaryotic expression vector and overexpressed in Escherichia coli. The purified protein was tetrameric in solution as determined by size exclusion chromatography. The protein displayed high affinity binding to NADPH as determined by fluorometric titration. The KD values for NADPH of the full-length wild-type protein and the N-terminus deleted protein were 0.1±0.007 and 0.05±0.006 M, respectively — indicating that the cofactor binding domain is restricted to the C-terminus, and is not drastically affected by the absence of the N-terminus amino acids, which form the ball and chain regulating voltage-dependent inactivation of the α-subunit. The protein displayed poor affinity for other coenzymes and the corresponding values of the KD for NADH and NAD were between 1–3 μM whereas the KD for FAD was >10 μM. However, relatively high affinity binding was observed with 3-acetyl pyridine NADP, indicating selective recognition of the 2′ phosphate at the binding site. The selectivity of Kvβ2.1 for NADPH over NADP may be significant in regulating the K+ channels as a function of the cellular redox state.  相似文献   

7.
Uracil phosphoribosyltransferase (UPRT) catalyzes the conversion of uracil and 5-phosphoribosyl-α-1-pyrophosphate (PRPP) to uridine 5′-monophosphate (UMP) and pyrophosphate (PPi). UPRT plays an important role in the pyrimidine salvage pathway since UMP is a common precursor of all pyrimidine nucleotides. Here we describe cloning, expression and purification to homogeneity of upp-encoded UPRT from Mycobacterium tuberculosis (MtUPRT). Mass spectrometry and N-terminal amino acid sequencing unambiguously identified the homogeneous protein as MtUPRT. Analytical ultracentrifugation showed that native MtUPRT follows a monomer-tetramer association model. MtUPRT is specific for uracil. GTP is not a modulator of MtUPRT ativity. MtUPRT was not significantly activated or inhibited by ATP, UTP, and CTP. Initial velocity and isothermal titration calorimetry studies suggest that catalysis follows a sequential ordered mechanism, in which PRPP binding is followed by uracil, and PPi product is released first followed by UMP. The pH-rate profiles indicated that groups with pK values of 5.7 and 8.1 are important for catalysis, and a group with a pK value of 9.5 is involved in PRPP binding. The results here described provide a solid foundation on which to base upp gene knockout aiming at the development of strategies to prevent tuberculosis.  相似文献   

8.
The cytochrome P-450K containing monooxygenase system of rat kidney cortex microsomes catalyzes the hydroxylation of various saturated fatty acids of medium chain length to the corresponding ω- and (ω-1)-hydroxy derivatives. The hydroxylation activity, as well as the ratio between the two hydroxylated products, vary with the carbon chain length of the fatty acid. Optimal hydroxylation activity is observed with myristic acid which yields the 13- and 14-hydroxylated products at a ratio of about 1. The ω/(ω-1)-hydroxylation ratio decreases with increasing carbon chain length of the fatty acid. On the other hand, with lauric acid as a substrate the ratio between ω- and (ω-1)-hydroxylation does not change significantly with varying time of incubation or substrate concentration, or incubation in a medium containing D2O or after induction of enhanced hydroxylation activity by starvation of the animals. Furthermore, 12-hydroxylauric acid and capric acid—which is almost exclusively ω-hydroxylated by rat kidney cortex microsomes—inhibit both 11- and 12-hydroxylation of lauric acid to a similar extent whereas 11-hydroxylauric acid does not seem to inhibit either 11- or 12-hydroxylation.C10-C16 fatty acids produce the type I spectral change upon addition to rat kidney cortex microsomes and seem to interact with similar amounts of the cytochrome P-450K present in these particles. In agreement with the metabolic studies, 12-hydroxylauric acid interacts with cytochrome P-450K giving rise to a reverse type I spectral change, whereas 11-hydroxylauric acid does not produce an observable spectral change. Finally, results of binding experiments with a series of derivatives of dodecane suggest that type I binding to cytochrome P-450K requires, besides a proper chain length, the presence of a carbonyl group together with an electron pair on a neighboring atom at the end of the carbon chain. A chain length of 14 carbon atoms seems to be optimal and it is suggested that this chain length may correspond to the distance between a possible binding site and the catalytic site of cytochrome P-450K  相似文献   

9.
Binding sites of bile acids on human serum albumin were studied using various probes: dansylsarcosine (site I probe), 7-anilinocoumarin-4-acetic acid (ACAA, site II probe), 5-dimethylaminonaphthelene-1-sulfonamide (DNSA, site III probe), cis-parinaric acid (probe for fatty acid binding site) and bilirubin. Bile acids competitively inhibited the binding of dansylsarcosine to human serum album whereas bile acids enhanced the binding of ACAA, DNSA, cis-parinaric acid and bilirubin. Considering the concentrations of bile acids required to inhibit the binding of dansylsarcosine to human serum albumin, the secondary binding site of bile acids may correspond to site I. Dissociation constants (Kd) of the primary binding sites of lithocholic and chenodeoxycholic acid to human serum albumin were approximately 0.2 and 4 μM, respectively, which was measured by equilibrium dialysis at 37° C. All the bile acids and their sulfates and glucuronides inhibited the binding of chenodeoxycholic acid to human serum albumin. Lithocholic and chenodeoxycholic acid and their sulfates and glucuronides exhibited more inhibition than cholic acid and its conjugates. In conclusion, bile acids may bind to a novel binding site on human serum albumin.  相似文献   

10.
Multi-conformation continuum electrostatics (MCCE) was used to analyze various structures of the NS3 RNA helicase from the hepatitis C virus in order to determine the ionization state of amino acid side chains and their pKas. In MCCE analyses of HCV helicase structures that lacked ligands, several active site residues were identified to have perturbed pKas in both the nucleic acid binding site and in the distant ATP-binding site, which regulates helicase movement. In all HCV helicase structures, Glu493 was unusually basic and His369 was abnormally acidic. Both these residues are part of the HCV helicase nucleic acid binding site, and their roles were analyzed by examining the pH profiles of site-directed mutants. Data support the accuracy of MCCE predicted pKa values, and reveal that Glu493 is critical for low pH enzyme activation. Several key residues, which were previously shown to be involved in helicase-catalyzed ATP hydrolysis, were also identified to have perturbed pKas including Lys210 in the Walker-A motif and the DExD/H-box motif residues Asp290 and His293. When DNA was present in the structure, the calculated pKas shifted for both Lys210 and Asp290, demonstrating how DNA binding might lead to electrostatic changes that stimulate ATP hydrolysis.  相似文献   

11.
The maximal velocity, V, for isocitrate cleavage by isocitrate lysase from Pseudomonas indigofera was dependent on two dissociable groups (pKa's of 6.9 and 8.6). The pH dependence of the pKi for succinate, a product of isocitrate cleavage, implied that a dissociable group (pKa of 6.0) on the enzyme functions in binding succinate. The pKi's for maleate and itaconate (succinate analogs) were similarly pH dependent. The pKi for oxalate, an analog of glyoxylate which is also a product of isocitrate cleavage, was pH independent. In contrast the pKi's of the four-carbon dicarboxylic acid inhibitors, fumarate and meso-tartrate, both of which affect the glyoxylate site, were dependent on a dissociable group on the enzyme-inhibitor complex. Comparison of the pH dependence of the pKm for isocitrate and the pKi for succinate (and succinate analogs) indicated that the binding of isocitrate was dependent on an acidic dissociable group on the enzyme (pKa of 5.8). The pH dependence of the pKi for homoisocitrate was similar. In addition the Ki for succinate and Km for isocitrate were dependent upon Mg2+ concentration. Inhibition by phosphoenolpyruvate, which binds to the succinate site and may regulate isocitrate lyase from P. indigofera, was twice as pH dependent as that for succinate. Two dissociable groups, one on the enzyme (pKa of 5.8) and one on phosphoenolpyruvate (pKa of 6.35), contributed to the pH dependence observed with phosphoenolpyruvate.  相似文献   

12.
The effect of phosphorylation on the basicities of amines in histone H3 peptides and their acetylation kinetics is probed with a mild chemical acetylating agent. Phosphorylation of Ser‐10 lowers the rate of chemical acetylation of Lys‐9, Lys‐14, and Lys‐18 by methyl acetyl phosphate in that order consistent with a higher pKa of these Lys residues induced by phosphorylation; basicities increase up to 3 pKa units as a function of distance from Ser‐10 phosphate. Enzymic acetylation of Lys residues with high pKa values in nucleosomes is also expected to be enhanced by phosphorylation, consistent with the known mechanism involving binding of protonated amines to N‐acetyltransferases; fetal hemoglobin has a related linkage of increased basicity at a specific site, its acetylation, and a resulting decrease in subunit interaction strength. In the absence of a phosphate on Ser‐10, the amines of Lys‐9, Lys‐14, and Lys‐18 have lowered pKa values. Chemical acetylation of glycine and glycinamide have analogous kinetic profiles to the histone peptides but the phosphate inductive effect in histone H3 is more potent since the linkage between phosphorylation and acetylation is propagated with a range extending 9–10 amino acids in either direction from the phosphorylation site enhancing protonation of amino groups. We conclude that lysine amine basicities in histone tails are not static but inducible and variable due to a dynamic and immediate interaction between phosphorylation/acetylation that may contribute to inactive heterochromatin by compaction through such Ser phosphate–Lys amine electrostatic interactions and their relaxation by acetylation in euchromatin.  相似文献   

13.
Subject index     
Heats of fusion and heat capacities have been measured for saturated, unsaturated and hydroxy fatty acids, differing in degree of unsaturation, geometric isomerism, and position of unsaturated and hydroxy groups. Entropies of fusion are used to draw conclusions concerning molecular structure of fatty acid chains and lateral chain-chain interactions. Position of the functional group on the chain does not seem to significantly affect the entropy values for trans and cis single double bonds and single triple bonds, but differences are noted with hydroxy group position. Whereas single acid triglycerides of saturated acids have entropies which are about three times that of the corresponding acid, cis and trans single acid triglycerides do not show the same relationship with their corresponding acids. Comparing entropies of fusion for certain groups of fatty acids, only differing in carbon number, allows the estimation of chain equivalence with saturated fatty acids. Hence, for example it is shown that a 22 to 23-carbon cis mono-unsaturated fatty acid is equivalent to an 18-carbon saturated fatty acid.  相似文献   

14.
Human 20α-hydroxysteroid dehydrogenase (AKR1C1) is an important drug target due to its role in the development of lung and endometrial cancers, premature birth and neuronal disorders. We report the crystal structure of AKR1C1 complexed with the first structure-based designed inhibitor 3-chloro-5-phenylsalicylic acid (Ki = 0.86 nM) bound in the active site. The binding of 3-chloro-5-phenylsalicylic acid to AKR1C1 resulted in a conformational change in the side chain of Phe311 to accommodate the bulky phenyl ring substituent at the 5-position of the inhibitor. The contributions of the nonconserved residues Leu54, Leu306, Leu308 and Phe311 to the binding were further investigated by site-directed mutagenesis, and the effects of the mutations on the Ki value were determined. The Leu54Val and Leu306Ala mutations resulted in 6- and 81-fold increases, respectively, in Ki values compared to the wild-type enzyme, while the remaining mutations had little or no effects.  相似文献   

15.
Arylalkylamine N-acyltransferase like 2 (AANATL2) catalyzes the formation of N-acylarylalkylamides from the corresponding acyl-CoA and arylalkylamine. The N-acylation of biogenic amines in Drosophila melanogaster is a critical step for the inactivation of neurotransmitters, cuticle sclerotization, and melatonin biosynthesis. In addition, D. melanogaster has been used as a model system to evaluate the biosynthesis of fatty acid amides: a family of potent cell signaling lipids. We have previously showed that AANATL2 catalyzes the formation of N-acylarylakylamides, including long-chain N-acylserotonins and N-acyldopamines. Herein, we define the kinetic mechanism for AANATL2 as an ordered sequential mechanism with acetyl-CoA binding first followed by tyramine to generate the ternary complex prior to catalysis. Bell shaped kcat,app – acetyl-CoA and (kcat/Km)app – acetyl-CoA pH-rate profiles identified two apparent pKa,app values of ∼7.4 and ∼8.9 that are critical to catalysis, suggesting the AANATL2-catalyzed formation of N-acetyltyramine occurs through an acid/base chemical mechanism. Site-directed mutagenesis of a conserved glutamate that corresponds to the catalytic base for other D. melanogaster AANATL enzymes did not produce a substantial depression in the kcat,app value nor did it abolish the pKa,app value attributed to the general base in catalysis (pKa ∼7.4). These data suggest that AANATL2 catalyzes the formation of N-acylarylalkylamides using either different catalytic residues or a different chemical mechanism relative to other D. melanogaster AANATL enzymes. In addition, we constructed other site-directed mutants of AANATL2 to help define the role of targeted amino acids in substrate binding and/or enzyme catalysis.  相似文献   

16.
Rat intestinal alkaline phosphatase is a dimeric enzyme with identical subunits and thus possesses two presumably identical active sites. Binding studies with Pi and l-phenylalanine and pre-steady-state “burst” titrations confirm the existence of two active sites per molecule of enzyme. The sites appear to be nonequivalent with respect to Pi binding, both at low pH, where an enzyme (E)-Pi covalent complex is formed, and at high Pi, where an E-Pi noncovalent complex predominates. The binding affinity of the first site is 100-fold greater than that of the second, i.e., there is negative cooperativity. The Ki value for competitive inhibition of substrate hydrolysis by Pi corresponds to the higher affinity site. The negative cooperativity appears not to be an artifact resulting from contaminating Pi in the purified enzyme preparation. l-Phenylalanine does not bind to the enzyme unless Pi is present, as expected from the previously proposed mechanism of uncompetitive inhibition by the amino acid. No negative cooperativity is seen in l-phenylalanine binding, but the number of moles of amino acid bound at saturation depends on the degree of saturation by Pi The enzyme is also inhibited uncompetitively by NADH, which can compete with l-phenylalanine for the same site on alkaline phosphatase.  相似文献   

17.
Non-thermal effects of ceramics irradiation on dissociation state of twenty L-amino acids have been investigated. Dissociation constants of the amino acids other than His and Glu varied by a 3-h irradiation under cooling. pK’s of α-carboxyl group of amino acids having longer side chains on the α-carbon were decreased by the irradiation. Although pK’s of α-amino group of Arg, Lys, Asp, and CySH were decreased by the irradiation and pK of Tyr was increased, pK’s of the other fifteen amino acids were not affected. Although the isoelectric points of Lys, Arg, Trp, Asp, and CySH were decreased by the irradiation, those of the other fifteen amino acids were not affected. It was suggested that various changes in pH of amino acids in aqueous solution and dissociation state of the functional groups will be caused from stimulation by the irradiation and stabilization of the hydration layer around amino acids.  相似文献   

18.
Properties of brain L-glutamate decarboxylase: inhibition studies   总被引:15,自引:12,他引:3  
—l -Glutamate decarboxylase purified from mouse brain was found to be highly sensitive to the sulfhydryl reagents, 5,5-dithiobis (2-nitrobenzoic acid) (DTNB) and p-chloromerburibenzoate (PCMB), which were competitive inhibitors (Ki for DTNB is 1·1 · 10?8m ). Iodoacetamide and iodoacetic acid were less effective inhibitors than DTNB and PCMB. The mercapto acids, 3-mercaptopropionic, 2-mercaptopropionic, and 2-mercaptoacetic acids were potent competitive inhibitors with Ki values of 1·8, 53 and 300 μm , respectively. 2-Mercaptoethanol was less effective. Aminooxyacetic acid was the most potent carbonyl-trapping reagent tested inhibiting the enzyme activity completely at 1·6 μm , followed by hydroxylamine, hydrazine, semicarbazide, and d -penicillamine. Carboxylic acids with a net negative charge were strong competitive inhibitors e.g. d -glutamate (Ki 0·9 mm ), α-ketoglutarate (Ki, l·2mm ), fumarate (Ki,1·8 mm ), dl -β-hydroxyglutamate (Ki, 2·8 mm ), l -aspartate (ki, 3·1 mm ) and glutarate (Ki, 3·5 mm ). 2-Aminophosphonobutyric and 2-aminophosphonopropionic acids, phosphonic analogs of glutamate and aspartate, respectively, had no effect at l0mm . γ-Aminobutyric acid, l -glutamine, l -γ-methylene-glutamine, and α,γ-diaminoglutaric acid, amino acids with no net negative charge at neutral pH, had no effect at 5 mm . Glutaric and α-ketoglutaric acids were the most potent inhibitors among the various dicarboxylic and α-keto-dicarboxylic acids tested (Ki, 3·5 and 1·2 mm , respectively). Compounds with one carbon less, succinic and oxalacetic acids, or with one carbon more, adipic and α-ketoadipic acids, were less inhibitory. The monovalent cations, Li+, Na+, NH4+, and Cs+ had no effect on l -glutamate decarboxylase activity in concentrations up to 10mm . Divalent cations, on the other hand, were very potent inhibitors. Among eleven divalent cations tested, Zn2+ was the most potent inhibitor, inhibiting to the extent of 50 per cent at 10μm . The decreasing order of inhibitory potency was: Zn2+ > Cd2+, Hg2+, Cu2+ > Ni2+ > Mn2+ Co2+ > Ba2+ > Ca2+ > Mg2+ > Sr+2, The anions, I?, Br?, Cl? and F? were only weak inhibitors. The Ki value for Cl? was 17mm . The above findings suggest minimally the presence of aldehyde, sulfhydryl and positively charged groups at or near the active site of the holoenzyme. Intermediates of glycolysis had little effect on l -glutamate decarboxylase activity, but intermediates of the tricarboxylic acid cycle, e.g. α-ketoglutarate (Ki= 1·2 mm ) and fumarate (Ki= 1·8 mm ) were relatively potent inhibitors. The nucleotides, ATP, ADP, AMP, cyclic AMP, GTP, GDP, GMP, and cyclic GMP were weak inhibitors. l -Norepinephrine (Ki= 1·3 mm ) and serotonin were potent inhibitors, while acetylcholine, dopamine and histamine were less effective. Ethanol and dioxane inhibited the enzyme activity to the extent of 20-50 per cent at 10 per cent (v/v), while slight activation was observed at low concentrations (0·1-1 per cent) of both solvents. The possible role of Zn2+ and some metabolites in the regulation of steady-state levels of γ-aminobutyric acid also was discussed.  相似文献   

19.
The active transport of neutral amino acids into Streptomyces hydrogenans is inhibited by external Na+. There is no indication that in these cells amino acid accumulation is driven by an inward gradient of Na+. The extent of transport inhibition by Na+ depends on the nature of the amino acid. It decreases with increasing chain length of the amino acid molecules i.e. with increasing non-polar properties of the side chain. Kinetic studies show that Na+ competes with the amino acid for a binding site at the amino acid carrier. There is a close relation between the Ki values for Na+ and the number of C atoms of the amino acids. Other cations also inhibit neutral amino acid uptake competitively; the effectiveness decreases in the order Li+ > Na+ > K+ > Rb+ > Cs+. Anions do not have a significant effect on the uptake of neutral amino acids. After prolonged incubation of the cells with 150 mM Na+, in addition to the competitive inhibition of transport Na+ induces an increase in membrane permeability for amino acids.  相似文献   

20.
A series of 19 structural analogs of propyl gallate (3,4,5-trihydroxybenzoic acid propyl ester) were tested for their ability to inhibit the cyanide-insensitive, electron transfer pathway in isolated mung bean mitochondria. The results indicate that the trihydroxy substituent, not the ester, of propyl gallate is the structural feature of the molecule required to produce inhibition. Further, only one OH group, if it is located para to the ester moiety, will bring about specific inhibition. Of the compounds which contained the appropriate hydroxyl group, the lower the pKα of the hydroxyl group, the lower the observed inhibition constant (Ki′) for blocking the alternative pathway. Even though the observed Ki′ values varied over two orders of magnitude for the compounds tested, the calculated pH-independent, intrinsic inhibition constants (Ki) were markedly similar for all inhibitory compounds. The results indicate that a simple phenolate anion is the minimum structural feature required to observe specific inhibition of the alternative pathway and the more easily the anion can be formed, the better the observed inhibition. Similarities between the above compounds and the structural features associated with hydroxamic acids were also noted.  相似文献   

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