Hemoglobin hydrolysate is derived from the enzymatic degradation of hemoglobin.This work aimed to evaluate whether hemoglobin hydrolysate promotes the absorption of non-heme iron and the safety of absorbed iron in mic...Hemoglobin hydrolysate is derived from the enzymatic degradation of hemoglobin.This work aimed to evaluate whether hemoglobin hydrolysate promotes the absorption of non-heme iron and the safety of absorbed iron in mice by analyzing the iron binding content,iron circulation,and liver homeostasis.We found that hemoglobin hydrolysate promoted the absorption of non-heme iron with high efficiency in duodenum by spontaneously binding non-heme iron during digestion,and increased hepatic iron content by up-regulating divalent metal transporter 1,zinc transporter 14,but hepatic iron content only increased at 3 weeks.Duodenal iron entered the blood through ferroportin without restriction at 3 weeks,and excessive iron entered the liver and then affected the hepatocyte membranes permeability and lipid synthesis through oxidative stress.With the prolongation of dietary intervention,the up-regulated hepcidin acted on the ferroportin to restrict excess iron from entering the blood,and then the hepatic homeostasis recovered.In addition,hemoglobin hydrolysate enhanced the hepatic antioxidant capacity.Taken together,hemoglobin hydrolysate has a strong ability to promote the absorption of non-heme iron in vivo,and the absorbed iron is relatively safe due to the regulation of hepcidin.展开更多
Many non-heme manganese complexes exhibit high reactivity and enantioselectivity for the activation of C-H bonds.Recently,Mn(PDP)complexes(PDP=N,N'-bis(pyridine-2-ylmethyl)-2,2,-bipyrrolidine)have been reported to...Many non-heme manganese complexes exhibit high reactivity and enantioselectivity for the activation of C-H bonds.Recently,Mn(PDP)complexes(PDP=N,N'-bis(pyridine-2-ylmethyl)-2,2,-bipyrrolidine)have been reported to activate C-H bonds selectively in the presence of carboxylic acids.In this study,we performed density functional theory calculations to investigate the formation and hydroxylation mechanisms of Mn(PDP)complexes.Our calculation results showed that Mn(Ⅲ)(PDP)complexes react with H_(2)O_(2) and carboxylic acid to form Mn(V)-oxo oxidation intermediate.The main oxidation intermediate,[(PDP)Mn(IV)(O…OC(O)CH_(3))^(2-)·]^(2+),was found to have the characteristics of S(Mn)=3/2 manganese(IV)center antiferromagnetically coupled to a σ^(*)_(O-O) radical,where the O-O bond is not completely broken.Furthermore,[(PDP)Mn(IV)(O…OC(O)CH_(3)^(2-)·]^(2+) was shown to have two single electron-accepting orbitals(α Mn-d_(xy) and βσ^(*)_(O-O))that can simultaneously interact with a doubly occupied electron-donating orbital(σ_(C-H))of substrate.Therefore,[(PDP)Mn(IV)(O…OC(O)CH_(3)^(2-)·]^(2+) species can act as a two-electron oxidant for the C-H bond flinctionalization.As a result,the C-H bond hydroxylation by [(PDP)Mn(IV)(O…OC(O)CH_(3)^(2-)·]^(2+) species was a single step.Following the H-abstraction with a low barrier of 4.5 kcal/mol,hydroxyl group would immediately rebound to the radical carbon without barrier.These results provide new insights toward the further development of non-heme manganese catalysts.展开更多
The development of gastrointestinal diseases has been found to be associated with Helicobacter pylori (H. pylori) infection and various biochemical stresses in stomach and intestine. These stresses, such as oxidative,...The development of gastrointestinal diseases has been found to be associated with Helicobacter pylori (H. pylori) infection and various biochemical stresses in stomach and intestine. These stresses, such as oxidative, osmotic and acid stresses, may bring about bi-directional effects on both hosts and H. pylori, leading to changes of protein expression in their proteomes. Therefore, proteins differentially expressed in H. pylori under various stresses not only reflect gastrointestinal environment but also provide useful biomarkers for disease diagnosis and prognosis. In this regard, proteomic technology is an ideal tool to identify potential biomarkers as it can systematically monitor proteins and protein variation on a large scale of cell’s translational landscape, permitting in-depth analyses of host and pathogen interactions. By performing two-dimensional polyacrylamide gel electrophoresis (2-DE) followed by liquid chromatography-nanoESI-mass spectrometry (nanoLC-MS/MS), we have successfully pinpointed alkylhydroperoxide reductase (AhpC), neutrophil-activating protein and non-heme iron-binding ferritin as three prospective biomarkers showing up-regulation in H. pylori under oxidative, osmotic and acid stresses, respectively. Further biochemical characterization reveals that various environmental stresses can induce protein structure change and functional conversion in the identified biomarkers. Especially salient is the antioxidant enzyme AhpC, an abundant antioxidant protein present in H. pylori. It switches from a peroxide reductase of low-molecular-weight (LMW) oligomers to a molecular chaperone of high-molecular-weight (HMW) complexes under oxidative stress. Different seropositivy responses against LMW or HMW AhpC in H. pylori-infected patients faithfully match the disease progression from disease-free healthy persons to patients with gastric ulcer and cancer. These results has established AhpC of H. pylori as a promising diagnostic marker for gastrointestinal maladies, and highlight the utility of clinical proteomics for identifying disease biomarkers that can be uniquely applied to disease-oriented translational medicine.展开更多
采用密度泛函DFT-B3LYP理论对非血红素铁超氧化物活化丙烯分子多态反应机理进行了探讨.研究结果表明氢原子抽取过程遵守单态反应机制,主要在基态高自旋七重态势能面进行,且具有较低活化能(ΔG~≠=65.6 k J·mol^(-1)),非血红素铁超...采用密度泛函DFT-B3LYP理论对非血红素铁超氧化物活化丙烯分子多态反应机理进行了探讨.研究结果表明氢原子抽取过程遵守单态反应机制,主要在基态高自旋七重态势能面进行,且具有较低活化能(ΔG~≠=65.6 k J·mol^(-1)),非血红素铁超氧化物可以作为有效氧化剂抽取氢原子。单态反应机制可能归因于近来建议的交换-加强反应原则(EER,铁中心具有较大交换稳定作用)。对于O-O键的活化,在CASSCF(10,8)/6-31+G(d)//TZVP水平下,势能面交叉区内,高自旋七重态(S1)和五重态(Q0)的自旋-轨道耦合(SOC)常数分别为2.26和2.19 cm^(-1)。轨道分析表明两条发生翻转自旋轨道具有相同空间组成(π*sub),SOC禁阻,因此通过SOC作用反应体系不可能有效地从七重态(S=3)势能面系间穿越到五重态(S=2)势能面,系间穿越可能发生在反应最后的退出阶段。展开更多
基金supported by the National Natural Science Foundation of China(32072211)Jiangsu Province Department of Education(Innovation Group of Meat Nutrition and Biotechnology)。
文摘Hemoglobin hydrolysate is derived from the enzymatic degradation of hemoglobin.This work aimed to evaluate whether hemoglobin hydrolysate promotes the absorption of non-heme iron and the safety of absorbed iron in mice by analyzing the iron binding content,iron circulation,and liver homeostasis.We found that hemoglobin hydrolysate promoted the absorption of non-heme iron with high efficiency in duodenum by spontaneously binding non-heme iron during digestion,and increased hepatic iron content by up-regulating divalent metal transporter 1,zinc transporter 14,but hepatic iron content only increased at 3 weeks.Duodenal iron entered the blood through ferroportin without restriction at 3 weeks,and excessive iron entered the liver and then affected the hepatocyte membranes permeability and lipid synthesis through oxidative stress.With the prolongation of dietary intervention,the up-regulated hepcidin acted on the ferroportin to restrict excess iron from entering the blood,and then the hepatic homeostasis recovered.In addition,hemoglobin hydrolysate enhanced the hepatic antioxidant capacity.Taken together,hemoglobin hydrolysate has a strong ability to promote the absorption of non-heme iron in vivo,and the absorbed iron is relatively safe due to the regulation of hepcidin.
文摘Many non-heme manganese complexes exhibit high reactivity and enantioselectivity for the activation of C-H bonds.Recently,Mn(PDP)complexes(PDP=N,N'-bis(pyridine-2-ylmethyl)-2,2,-bipyrrolidine)have been reported to activate C-H bonds selectively in the presence of carboxylic acids.In this study,we performed density functional theory calculations to investigate the formation and hydroxylation mechanisms of Mn(PDP)complexes.Our calculation results showed that Mn(Ⅲ)(PDP)complexes react with H_(2)O_(2) and carboxylic acid to form Mn(V)-oxo oxidation intermediate.The main oxidation intermediate,[(PDP)Mn(IV)(O…OC(O)CH_(3))^(2-)·]^(2+),was found to have the characteristics of S(Mn)=3/2 manganese(IV)center antiferromagnetically coupled to a σ^(*)_(O-O) radical,where the O-O bond is not completely broken.Furthermore,[(PDP)Mn(IV)(O…OC(O)CH_(3)^(2-)·]^(2+) was shown to have two single electron-accepting orbitals(α Mn-d_(xy) and βσ^(*)_(O-O))that can simultaneously interact with a doubly occupied electron-donating orbital(σ_(C-H))of substrate.Therefore,[(PDP)Mn(IV)(O…OC(O)CH_(3)^(2-)·]^(2+) species can act as a two-electron oxidant for the C-H bond flinctionalization.As a result,the C-H bond hydroxylation by [(PDP)Mn(IV)(O…OC(O)CH_(3)^(2-)·]^(2+) species was a single step.Following the H-abstraction with a low barrier of 4.5 kcal/mol,hydroxyl group would immediately rebound to the radical carbon without barrier.These results provide new insights toward the further development of non-heme manganese catalysts.
基金Supported by(in part) Kaohsiung Medical University,Academia Sinica,and the National Science Council,Taipei,Taiwan,No.96-2311-B-037-005-MY3,No.99-2314-B-037-042,and No.99-2745-B-037-005 to Chiou SH
文摘The development of gastrointestinal diseases has been found to be associated with Helicobacter pylori (H. pylori) infection and various biochemical stresses in stomach and intestine. These stresses, such as oxidative, osmotic and acid stresses, may bring about bi-directional effects on both hosts and H. pylori, leading to changes of protein expression in their proteomes. Therefore, proteins differentially expressed in H. pylori under various stresses not only reflect gastrointestinal environment but also provide useful biomarkers for disease diagnosis and prognosis. In this regard, proteomic technology is an ideal tool to identify potential biomarkers as it can systematically monitor proteins and protein variation on a large scale of cell’s translational landscape, permitting in-depth analyses of host and pathogen interactions. By performing two-dimensional polyacrylamide gel electrophoresis (2-DE) followed by liquid chromatography-nanoESI-mass spectrometry (nanoLC-MS/MS), we have successfully pinpointed alkylhydroperoxide reductase (AhpC), neutrophil-activating protein and non-heme iron-binding ferritin as three prospective biomarkers showing up-regulation in H. pylori under oxidative, osmotic and acid stresses, respectively. Further biochemical characterization reveals that various environmental stresses can induce protein structure change and functional conversion in the identified biomarkers. Especially salient is the antioxidant enzyme AhpC, an abundant antioxidant protein present in H. pylori. It switches from a peroxide reductase of low-molecular-weight (LMW) oligomers to a molecular chaperone of high-molecular-weight (HMW) complexes under oxidative stress. Different seropositivy responses against LMW or HMW AhpC in H. pylori-infected patients faithfully match the disease progression from disease-free healthy persons to patients with gastric ulcer and cancer. These results has established AhpC of H. pylori as a promising diagnostic marker for gastrointestinal maladies, and highlight the utility of clinical proteomics for identifying disease biomarkers that can be uniquely applied to disease-oriented translational medicine.
文摘采用密度泛函DFT-B3LYP理论对非血红素铁超氧化物活化丙烯分子多态反应机理进行了探讨.研究结果表明氢原子抽取过程遵守单态反应机制,主要在基态高自旋七重态势能面进行,且具有较低活化能(ΔG~≠=65.6 k J·mol^(-1)),非血红素铁超氧化物可以作为有效氧化剂抽取氢原子。单态反应机制可能归因于近来建议的交换-加强反应原则(EER,铁中心具有较大交换稳定作用)。对于O-O键的活化,在CASSCF(10,8)/6-31+G(d)//TZVP水平下,势能面交叉区内,高自旋七重态(S1)和五重态(Q0)的自旋-轨道耦合(SOC)常数分别为2.26和2.19 cm^(-1)。轨道分析表明两条发生翻转自旋轨道具有相同空间组成(π*sub),SOC禁阻,因此通过SOC作用反应体系不可能有效地从七重态(S=3)势能面系间穿越到五重态(S=2)势能面,系间穿越可能发生在反应最后的退出阶段。
