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At least 19 recordsLinked to original sources
PubMed1994

Identification of oxidized histidine generated at the active site of Cu,Zn-superoxide dismutase exposed to H2O2. Selective generation of 2-oxo-histidine at the histidine 118.

Inactivation of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) by its own reaction product H2O2 is a well-known phenomenon. Generation of the hydroxyl radical has been a matter of great concern, and the target molecule has been regarded as its own active site histidine residues, whose oxidized forms have not yet been identified (Hodgson, E.K., and Fridovich, I. (1975) Biochemistry 14, 5294-5299). Here we report on the identification of oxidized histidines generated at the active site of Cu,Zn-SOD by reaction with H2O2. When bovine erythrocyte Cu,Zn-SOD (0.5 mg/ml) was treated with 5 mM H2O2 in 50 mM sodium phosphate buffer (pH 7.2), histidine was significantly lost; however, except for a significant increase in aspartate and glutamate, nothing new appeared in the amino acid analysis of oxidized Cu,Zn-SOD. On the other hand, the hydrolysates of oxidized Cu,Zn-SOD involved an unknown product that was detectable by reverse-phase high performance liquid chromatography with electrochemical detection. The product was found to be identical to 2-oxo-histidine that had been discovered as the major oxidation product of histidine and its peptides treated with a copper/ascorbate-free radical generating system. The main product present in the hydrolysate of H2O2-treated Cu,Zn-SOD was 2-oxo-histidine. Approximately 0.66 mol/mol subunit was formed when Cu,Zn-SOD was treated with 5 mM H2O2 for 30 min. Both metal chelators and the hydroxyl radical scavengers only slightly inhibited the 2-oxo-histidine formation (10-39%), suggesting that the active species were produced mainly inside the ligands of the Cu2+ in the enzyme. Trypsin digestion of H2O2-treated Cu,Zn-SOD showed selective reactions at the sequences of Gly24-Lys67 and Thr114-Arg126, in that histidine residues locate at the active center. Two new products derived from those peptides appeared in the tryptic map. Amino acid analysis of both products demonstrated the loss of only histidine. One of them derived from Thr114-Arg126 contained an equimolar amount of 2-oxo-histidine, indicating that His-118 was converted selectively to 2-oxo-histidine; however, another product derived from Gly24-Lys67 contained only 0.085 mol of 2-oxo-histidine/mol of peptide, suggesting that the product is a mixture consisting of unidentified forms of oxidized histidine. Taken together, the present study provided direct evidence that 2-oxo-histidine was generated in the Cu,Zn-SOD exposed to H2O2 and that its generation was selective at histidine 118 of the active site of the enzyme.

Amino Acid Sequence↗
PubMed2003

Could the tyrosine-histidine ligand to CuB in cytochrome c oxidase be coordinatively labile? Implications from a quantum chemical model study of histidine substitutional lability and the effects of the covalent tyrosine-histidine cross-link.

Density functional theory calculations have been used to evaluate the effects of inter-ring interactions within a covalently linked histidine-tyrosine cofactor such as that which is a ligand to the Cu(B) centre in cytochrome c oxidases and to investigate the energetics of histidine substitution at the Cu(B) centre. Small, but significant, perturbations of the redox potentials and/or p K(a) values of the histidine imidazole, the tyrosine phenol and the copper ion are found. The Cu(B)-N(cofactor) bond is estimated to be weaker than the Cu(B)-N(histidine coligand) bonds in the Cu(B)(I) state and in the Cu(B) (II) state when the cofactor is oxidized, by approximately 13 kJ/mol and approximately 23 kJ/mol, respectively. The calculations reveal that displacement of a histidine ligand from the Cu(B) centre, as is suggested in proposals of "histidine cycle" mechanisms for proton pumping in cytochrome c oxidases, is only energetically feasible if accompanied by protonation of the histidine imidazole and coupled to an endothermic process. It is proposed that the histidine-tyrosine cofactor ought to be considered as the substitutionally labile ligand to Cu(B) as the covalent crosslink would ensure displacement of the cofactor from Cu(B)-driven helix deformation. It is estimated that this process could store up to approximately 70 kJ/mol, which, based upon thermodynamic considerations, is sufficient for the pumping of two protons in the later steps (reductive phase) of the catalytic cycle. Ramifications of this proposition for the mechanism of proton pumping in cytochrome c oxidases are discussed.

Amino Acid Substitution↗
PubMed1975

Phosphopyridoxal complexes with histamine and histidine. (4) The kinetics of complex formation between histidine and pyridoxal 5' -phosphate in the presence of bacterial histidine decarboxylase.

The dynamics of the complex formation between pyridoxal 5'-phosphate (PLP) and histidine in the presence of bacterial histidine decarboxylase was examined. Since PLP is able to form a cyclic product with histidine and histamine, the possibility of complex formation between PLP and histamine formed during a decarboxylation reaction was examined too. It was found that the cyclization reaction between PLP and histidine is equimolecular and the rate of cyclic product formation is not significantly influenced by the presence of enzyme. In the presence of bacterial histidine decarboxylase both the cyclization reaction and cyclic product formation were observed. Predominance of histamine or cyclic product formation was dependent on pH and substrate concentration. In the presence of histidine and enzymatic protein, histamine formed during the decarboxylation reaction was unable to form a cyclic product with PLP.

Carboxy-Lyases↗
PubMed1993

Site-directed mutagenesis and chemical modification of histidine residues on an alpha-class chick liver glutathione S-transferase CL 3-3. Histidines are not needed for the activity of the enzyme and diethylpyrocarbonate modifies both histidine and lysine residues.

Each chick liver glutathione S-transferase CL 3 subunit contains three histidine residues: His142, His158 and His228. CL 3-3 can be inactivated by treating with diethylpyrocarbonate. The inactivation process is pH dependent and the pKa of the modified residue is 6.4. The second-order inhibition rate constant is 741 M-1min-1 at pH 7.0. Based on difference-spectrum and kinetic analysis, inactivation coincides with the modification of one histidine residue. However, hydroxylamine treatment of the diethylpyrocarbonate-modified enzyme only partially restored the activity (30-50%) of CL 3-3. By tryptic mapping and amino acid sequence analysis, His228 and Lys14 have been identified as the modified residues. Mutants with histidine to serine replacement (H142S and H158S) or C-terminal histidine deletion (des-H228) were constructed and over-expressed in Spodoptera frugiperda cells using a baculovirus system. The mutants are enzymically active. Furthermore, the des-H228 mutant can be inactivated by diethylpyrocarbonate. These results support the conclusion that histidines are not involved in the enzymic mechanism of CL 3-3.

Amino Acid Sequence↗
PubMed1986

High resolution NMR studies of histidine-substituted and histidine-perturbed hemoglobin variants. Histidine assignments, electrostatic interactions at the protein surface, and implications for hemoglobin S polymerization.

The aromatic region of the proton NMR spectrum of human adult hemoglobin (HbA) contains resonances from at least 11 titratable histidine residues. Assignments for five beta chain histidines have previously been proposed. In order to further characterize the aromatic spectra of HbA we studied 11 histidine-substituted and -perturbed hemoglobin variants in oxy and deoxy states and at different pH values by 400 MHz NMR spectroscopy. We propose assignments for the resonances corresponding to the C2 protons of His alpha 20, His alpha 72, His alpha 112, and His beta 77 in oxy and deoxy spectra and of His beta 97 and His beta 117 in deoxy spectra. Our assignments for His beta 2 and His beta 117 in the oxy state agree with those previously reported for the CO form, but in the deoxy state our spectra suggest a different assignment. Studies with Hb variants in which a histidine is perturbed by a neighboring substitution suggest additional assignments for His alpha 50 and His alpha 89 and demonstrate a strong dependence of the imidazole ring pK on hydrogen bond interactions and on the net charge of neighboring residues. Some of the newly proposed assignments of histidine resonances are used to discuss specific intermolecular interactions implicating His alpha 20, His beta 77, and His beta 117 in deoxy HbS polymers.

Electrochemistry↗
PubMed1989

Studies of histidine phosphorylation by a nuclear protein histidine kinase show that histidine-75 in histone H4 is masked in nucleosome core particles and in chromatin.

Histone H4 is a good substrate in vitro for the protein histidine kinase activity found both in Physarum polycephalum nuclear extracts and in Saccharomyces cerevisiae cell extracts. However, histone H4 in nucleosome core particles is not a substrate for these kinases. Isolated chromatin was also not a substrate for the protein histidine kinase. The results significantly limit possible interpretations of histidine phosphorylation on histone H4 in vivo and provide a new, sharper focus for future work. In addition, a polynucleotide kinase activity was identified in the Physarum extracts.

Animals↗
PubMed1983

1H-NMR study on the tautomerism of the imidazole ring of histidine residues. II. Microenvironments of histidine-12 and histidine-119 of bovine pancreatic ribonuclease A.

The NMR titration curves of proton chemical shifts were observed for the C2 protons of histidine residues in intact bovine pancreatic RNAase A (EC 3.1.27.5) and carboxyalkylated RNAase A. By comparing the methyl region of NMR spectra, the 250-340 nm region of circular dichoic spectra, and the NMR titration curves of tyrosine ring protons among intact and modified RNAase A, it was ascertained that the carboxyalkylation of histidine residues at position 12 or 119 did not make any appreciable conformational changes to RNAase A. With the pK values determined for intact and modified RNAase A, the microscopic pK values and molar ratios of tautomers were estimated for His-12 and His-119 by means of the procedure described in the preceding paper. The estimated microscopic pK values of tautomers were 6.2 for the N1-H tautomer of His-12, more than 8 for the N3-H tautomer of His-12, 7.0 for the N1-H tautomer of His-119, and 6.4 for the N3-H tautomer of His-119, respectively. These values were interpreted in terms of the microscopic environments surrounding the histidine residues. The microscopic structure estimated in the present study was discussed, comparing it with those from X-ray crystallography and hydrogen-tritium (or hydrogen-deuterium) exchange technique.

Animals↗
PubMed1987

Further characterization of the interaction of histidine-rich glycoprotein with heparin: evidence for the binding of two molecules of histidine-rich glycoprotein by high molecular weight heparin and for the involvement of histidine residues in heparin binding.

Rabbit histidine-rich glycoprotein (HRG, 94 kDa) binds heparin with high affinity (apparent Kd 60-110 nM). Eosin Y (1 equiv) bound to HRG was used as a reporter group to monitor associations of HRG with heparins of molecular mass 10, 17.5, and 30 kDa. The stoichiometries of the heparin-HRG complexes were determined by fluorescence and absorbance measurements as well as by analytical ultracentrifugation. Two types of complex form: complexes of 1 heparin:1 HRG and of 1 heparin:2 HRG. The 1:2 complex formation requires a minimum heparin chain length since 17.5-kDa but not 10-kDa heparin binds two HRG molecules. The formation of the 1:2 complexes of the larger heparin fractions is enhanced by divalent copper or zinc (1-10 equiv) bound to HRG. However, metal is not required for complex formation since all sizes of heparin examined interact tightly with HRG in the presence of ethylenediaminetetraacetic acid. Between 0.1 and 0.3 M ionic strength, both 1:1 and 1:2 complexes of heparin with HRG are progressively destabilized. No heparin-HRG complex is found at ionic strengths of 0.5 M. Between pH 8.5 and pH 6.5 both 1:2 and 1:1 complexes are found with 17.5-kDa heparin, but at pH 5.5 only 1:1 complexes are formed. The heparin-HRG interaction is progressively decreased by modification of the histidine residues of HRG, whereas modification of 22 of the 33 lysine residues of HRG has little effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Optimum ratio of histidine in the piglet ideal protein model and its effects on the body metabolism. II. Optimum ratio of histidine in 10-20 KG piglet ideal protein and its effects on blood parameters.

Two growth trails were conducted to determine the optimum ratio of histidine in 10-20 kg piglet ideal protein model. Four diets containing 0.23%, 0.31%, 0.39% and 0.47% digestible histidine (0, 0.08%, 0.16%, 0.24% crystalline histidine supplemented into the basal diet) were fed to 96 piglets of mean initial body weight 10.3 +/- 1.08 kg for 18 d in Experiment 1. Average daily gain, average daily feed intake and feed conversion efficiency were inhibited (P < 0.05) with the diet containing 0.23% digestible histidine. Performance was maximized with 0.31% digestible histidine. As the dietary histidine increased, blood urea nitrogen and serum cholesterol concentration were influenced significantly. The concentrations of serum histamine and free histidine did not change with increase in digestible histidine from 0.23 to 0.31%, but higher supplementation resulted in a significant linear increase in both serum parameters. It was concluded that the dietary level of 0.23% digestible histidine does not meet the requirement of 10-20 kg piglets. Based on the results from Experiment 1, Experiment 2 was designed to determine the optimum ratio of lysine:histidine in the ideal protein model of 10-20 kg piglet. Ninety-six Large White x Landrace piglets weighing 10.2 +/- 0.88 kg were divided into 4 groups. They were fed four diets containing 0.26, 0.29, 0.32 or 0.35% digestible histidine, formulated by adding 0.03, 0.06, 0.09 or 0.12% crystalline histidine to the basal diet. The trial lasted for 21 days. Results showed that performance was significantly improved with 0.32 and 0.35% digestible histidine. As dietary histidine increased, blood urea nitrogen tended to decrease but not significant at P < 0.05. Serum cholesterol concentration increased with an increase in dietary histidine level and reached a maximum at 0.35%. Serum histamine increased with increasing dietary histidine. Free serum histidine increased linearly with increased dietary histidine. From both experiments it was concluded that the digestible histidine requirement for 10-20 kg piglets was 0.31% and that the optimum ratio of dietary lysine to histidine should be 100:30. The concentrations of cholesterol, histamine and free histidine in serum were sensitive parameters to measure changes in dietary histidine levels.

Amino Acids↗
PubMed1982

14CO2 expiration after 14C-histidine administration in normal and uremic men ingesting two levels of histidine.

The rates of histidine degradation were investigated in six normal and three chronically uremic men who were not undergoing dialysis therapy. The nine men were studied in the postabsorptive state after they had ingested one or more of the following diets for the indicated periods of time: a 40 g protein diet providing about 1100 mg/day of histidine for 27 +/- 9 SD days (seven studies), an amino acid diet providing only 65 mg/day of histidine (histidine-deficient diet) for 33 +/- 3 days (eight studies), and an amino acid diet providing about 1125 mg/day of histidine (histidine-replete diet) for 32 +/- 7 days (six studies). Diets are listed in the order of administration; five men received all three diets. After fasting overnight, subjects received an intravenous injection of 25 microCi/70 kg body weight of L-[ring-2-14C]-histidine (eight men) or L-carboxyl-14C]-histidine (one man), and expiration of 14CO2 was measured continuously for 2 h. With both tracers, expiration of 14CO2 fell with ingestion of the histidine-deficient diet (p less than 0.005) and then increased with intake of the histidine-replete diet (p less than 0.05). Free histidine in plasma and muscle also decreased with the histidine-deficient diet and rose with the histidine-replete diet. If other tissue free histidine pools changed similarly and protein turnover was not very different with the three diets, then the 14CO2 expiration data and the estimated specific activity of 14C-histidine indicate that histidine degradation fell markedly with the histidine-deficient diet and then increased with the histidine-replete diet. In uremic patients as compared to normal subjects no differences in the magnitude of 14C-histidine degradation or in the pattern of 14CO2 expiration were observed.

Adult↗
PubMed1981

Effect of histidine intake of plasma and urine histidine levels, nitrogen balance and N tau-methylhistidine excretion in normal and chronically uremic men.

This study assessed whether changes in plasma histidine or nitrogen balance could indicate the dietary histidine requirement in short-term feeding studies. Five normal and two chronically uremic men were fed diets varying in histidine content in a metabolic research unit. Subjects received amino acid diets for 71 +/- 12 (SD) days during which time the histidine intake was varied between 60 and 2,800 mg/day at 8.0 +/- 0.5 day intervals. The results indicated that both postabsorptive plasma histidine and urinary histidine correlated with the dietary histidine intake. However, in individual patients the response curve of plasma histidine to the dietary histidine intake did not demonstrate a consistent breakpoint which could be used to indicate the dietary histidine requirement. Rather, the histidine intake above which the plasma levels increased rapidly seemed to be influenced by the previous dietary histidine. Urinary histidine excretion also correlated with plasma histidine. N tau-methylhistidine was increased in plasma and reduced in urine of the uremic patients as compared to normal subjects. Nitrogen balances were less positive with histidine intakes of 2 mg/kg/day or lower. These data support the finding that histidine is an essential amino acid in normal and chronically uremic man. However, clinical and metabolic studies of greater duration may be necessary to determine the daily histidine requirement.

Adult↗
PubMed1989

A peptide histidine isoleucine/peptide histidine methionine-like peptide in the rabbit retina: colocalization with vasoactive intestinal peptide, synaptic relationships and activation of adenylate cyclase activity.

Antisera against peptide histidine isoleucine and peptide histidine methionine were found to label a subpopulation of amacrine and displaced amacrine cells in the rabbit retina with processes ramifying in sublaminas 1, 3 and 5 of the inner plexiform layer. Preadsorption controls demonstrated that this immunoreactivity was specific for a peptide histidine isoleucine- or peptide histidine methionine-like (peptide histidine isoleucine/peptide histidine methionine-like) peptide, and was not caused by cross-reactivity of the peptide histidine isoleucine or peptide histidine methionine antibodies with vasoactive intestinal peptide vasoactive intestinal peptide. In double-label studies, vasoactive intestinal peptide and peptide histidine isoleucine/peptide histidine methionine-like immunoreactivity were colocalized in the same population of retinal neurons. Electron microscopic analysis revealed that the peptide histidine isoleucine/peptide histidine methionine-labelled cells interacted with processes of bipolar cells, amacrine cells and ganglion cells. Peptide histidine methionine and peptide histidine isoleucine were slightly less potent than vasoactive intestinal peptide in stimulating adenylate cyclase activity in the rabbit retina, while the related peptides secretin, glucagon, and the C-terminal vasoactive intestinal peptide fragment, vasoactive intestinal peptide (10-28), showed little or no stimulatory activity. Stimulation of adenylate cyclase by high concentrations of vasoactive intestinal peptide and peptide histidine methionine were non-additive. These results suggest that a peptide histidine isoleucine/peptide histidine methionine-like peptide may function as a neuroactive peptide in the mammalian retina, and that this peptide appears to be cosynthesized and colocalized with vasoactive intestinal peptide and to mimic the activity of vasoactive intestinal peptide through interaction with vasoactive intestinal peptide receptor-adenylate cyclase complexes.

Adenylyl Cyclases↗
PubMed1985

Molecular forms of peptide histidine isoleucine-like immunoreactivity in the gastrointestinal tract. Nonequimolar levels of peptide histidine isoleucine and vasoactive intestinal peptide in the stomach explained by the presence of a big peptide histidine isoleucine-like molecule.

Regional specific antibodies and chromatography were used to analyze the distributions and molecular forms of peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP) in the porcine intestine. Both peptides were present along the entire length of the intestine, the highest concentrations occurring in the colon. Concentrations of PHI immunoreactivity, measured with three different antisera, and VIP immunoreactivity were approximately equal in all parts of the gastrointestinal tract except in the stomach. In the stomach, the concentration of PHI immunoreactivity, measured with the N-terminally directed antibody R8403, although equal to the corresponding VIP concentration, was two to four times higher than the PHI immunoreactivity detected with the two C-terminally directed PHI antisera T33 and T41. Chromatographic analysis on Sephadex G-50 superfine of gastric extracts revealed only one VIP immunoreactive peak that eluted in the same position as the porcine VIP standard, at Kav 0.53. A PHI immunoreactive peak was also detected with the C-terminally directed PHI antisera in the same position as porcine PHI standard. However, with the N-terminally directed PHI antiserum R8403, an additional PHI immunoreactive peak was detected in gastric extracts constituting the predominant form present, and this peak eluted earlier at Kav 0.37. The PHI immunoreactive material that eluted earlier was present in the rest of the intestine in only small amounts. As VIP and PHI are believed to be derived from a common precursor, it is suggested that in the stomach the posttranslational enzymic processing of the precursor is different from that in the other parts of the intestine.

Animals↗
PubMed1985

In vivo synthesis of histidine by a cloned histidine ammonia-lyase in Escherichia coli.

Histidine ammonia-lyase catalyzes the first step in histidine catabolism, the deamination of histidine to urocanate and ammonia. In vitro experiments have shown that histidine ammonia-lyase also can catalyze the reverse (amination) reaction, histidine synthesis, relatively efficiently under extreme reaction conditions (4 M NH4OH, pH 10). An Escherichia coli hisB deletion strain was transformed with a pBR322 derivative plasmid (pCB101) containing the entire Klebsiella aerogenes histidine utilization (hut) operon to determine whether the catabolic histidine ammonia-lyase could function biosynthetically in vivo to satisfy the histidine auxotrophy. Although the initial construct did not grow on media containing urocanate and ammonia as a source of histidine, spontaneous mutants possessing this ability were isolated. Four mutants characterized grew at doubling times of 4 h compared with 1 h when histidine was present, suggesting that histidine synthesis, although unequivocally present, remained growth limiting. Each mutant contained a plasmid-encoded mutation which eliminated urocanase activity, the second enzyme in the Hut catabolic pathway. This genetic block led to the accumulation of high intracellular levels of urocanate, which was subsequently converted to histidine via histidine ammonia-lyase, thus satisfying the histidine auxotrophic requirement.

Ammonia-Lyases↗
PubMed1990

Peptide histidine valine: its haemodynamic actions and pharmacokinetics in man differ from those of vasoactive intestinal peptide and peptide histidine methionine.

1. The effects of intravenous and intra-arterial infusion of the peptides derived from prepro-vasoactive intestinal peptide, vasoactive intestinal peptide, peptide histidine methionine and peptide histidine valine, were examined in six healthy volunteers. 2. Vasoactive intestinal peptide given intravenously caused a significant increase in heart rate and a decrease in diastolic, but not systolic, blood pressure, whereas peptide histidine valine caused an increase in heart rate alone, despite higher achieved circulating peptide concentrations. Peptide histidine methionine did not affect heart rate or blood pressure. Forearm blood flow was increased by vasoactive intestinal peptide and peptide histidine valine when infused locally intra-arterially, although vasoactive intestinal peptide was more potent than peptide histidine valine. 3. Plasma concentrations of cardiodilatin (the N-terminal peptide derived from pro-atrial natriuretic peptide) were increased by intravenous infusion of vasoactive intestinal peptide, but were unaffected by peptide histidine methionine or peptide histidine valine. Circulating plasma concentrations of adrenaline and noradrenaline did not change during infusion of vasoactive intestinal peptide, peptide histidine methionine or peptide histidine valine. 4. Peptide histidine valine had a long half-life when compared with peptide histidine methionine and vasoactive intestinal peptide. 5. We conclude that peptide histidine valine is active in the human cardiovascular system and has a similar, though less potent, vasodilating action to vasoactive intestinal peptide. The higher circulating levels of peptide histidine valine found in man suggest that it may be important in modulating vascular tone.

Adult↗
PubMed1975

Inhibition of histidine, decarboxylation in vivo by 2-hydroxy-5-carbomethoxybenzyloxyamine, a new, potent inhibitor of histidine decarboxylase.

Measurements of the rate of expiration of 14CO2 were carried out after the injection into rats of 14C-histidine labeled in the carboxyl group (C-His) or in the imidazole ring (R-His). Intraperitoneal administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, a new potent inhibitor of histidine decarboxylase, reduced the rate of 14CO2 production from C-His and R-His in a dose-dependent manner. The metabolism of C-His was more affected than that of R-His. The inhibitor had no effect on the production of 14CO2 from 14C-urocanic acid, 14C-dopa or 14C-glutamic acid. Rats given 2-hydroxy-5-carbomethoxybenzyloxyamine (100 mg/kg) by the intraperitoneal route had diminished histidine decarboxylase activity of stomach (96 percent decrease), but did not have any change in the activities of histidase, urocanase or histidine-pyruvate aminotransferase of liver. After the administration of histidine (500 mg/kg), the level of this amino acid in serum remained elevated somewhat longer in inhibitor-treated animals than in the controls. The temporary rise in serum histidine relative to controls that were also histidine-loaded is considered to reflect the decreased rate of uptake of histidine into the tissues, and also a decreased rate of decarboxylation of histidine in certain organs. After the administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, the decreased rate of 14CO2 production from injected R-His and the delayed disappearance of histidine from the serum after a histidine load were considered to reflect mainly the decreased rate of histidine uptake into the tissues. The decreased rate of formation of 14CO obtained with C-His appeared to result from inhibition of both uptake and decarboxylation of histidine.

Animals↗
PubMed1983

Coordination modes of histidine. 4. Coordination structures in the copper(II)-L-histidine (1:2) system.

The coordination structures of various species in the copper(II)-L-histidine (1:2) system in aqueous solution have been deduced by investigating the pH dependence of the electronic and circular dichroism spectra. The contribution to the spectra of the glycine-like and histamine-like binding modes of L-histidine has been determined by recording the spectra of the ternary system copper(II)-histamine-L-histidine (1:1:1) and copper(II)-amino acid-L-histidine (1:1:1), respectively, in neutral aqueous solutions. Apical binding to copper(II) by the donor atom on the histidine side chain can contribute significantly to the stabilization of each of the two basic histidine binding modes. It has been concluded that Cu(HL)2+ (L-histidine = HL), the major species below pH approximately 3, contains a glycine-like bound histidine ligand with an unbound imidazolium cation. The species Cu(HL)L+, which is prominent in the pH region near 4.5, contains a glycine-like bound histidine molecule, with protonated imidazole ring, and a histamine-like bound histidine molecule. CuL2, the major species at neutral pH, exists in solution as an equilibrium mixture of a mixed-type chelation structure, with a glycine-like and a histamine-like bound histidine ligand, and a structure containing both histidine ligands bound histamine-like. The species containing deprotonated imidazole nuclei, such as Cu(H-1L2)-, which predominates above pH approximately 11, show an increased contribution by structures containing glycine-like bound histidine compared with CuL2.

Chemical Phenomena↗
PubMed1983

Histidine uptake by isolated rat peritoneal mast cells. Effect of inhibition of histidine decarboxylase by alpha-fluoromethylhistidine.

Preincubation with (S)-alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, was found to markedly reduce, but not eliminate, the uptake of [3H]histidine by rat peritoneal mast cells. The Vmax for histidine transport for cells in which decarboxylation of histidine had been completely inhibited was 11.9 pmoles per min per 10(6) cells, compared to a Vmax of 18.9 pmoles per min per 10(6) cells in the presence of active mast cell histidine decarboxylase. The Km of uptake was 139 microM in the presence of alpha-fluoromethylhistidine, several times higher than the Km of 44.0 microM in the uninhibited cell. alpha-Fluoromethylhistidine did not inhibit mast cell uptake of phenylalanine, a competitive inhibitor of histidine uptake but not a substrate for histidine decarboxylase; nor did it inhibit the uptake of histidine by non-mast cells, which lack histidine decarboxylase. Levels of intracellular [3H]histidine in mast cells were similar in the presence and absence of the decarboxylase inhibitor. Based on these observations, we propose that intracellular decarboxylation of histidine in the mast cell serves to specifically enhance the uptake of histidine by the relatively non-specific amino acid transporter present in the plasma membrane of the cell.

Animals↗