• <tr id="yyy80"></tr>
  • <sup id="yyy80"></sup>
  • <tfoot id="yyy80"><noscript id="yyy80"></noscript></tfoot>
  • 99热精品在线国产_美女午夜性视频免费_国产精品国产高清国产av_av欧美777_自拍偷自拍亚洲精品老妇_亚洲熟女精品中文字幕_www日本黄色视频网_国产精品野战在线观看 ?

    Research progress of metal chelating peptides

    2022-06-05 16:33:29WeiTaoLuChunMingDong
    Food and Health 2022年4期

    Wei-Tao Lu ,Chun-Ming Dong*

    1College of Marine and Environmental Sciences,Tianjin University of Science and Technology,Tianjin 300457,China.

    Abstract Some metal elements,especially trace elements,have obvious nutritional and physiological functions on the human body,which can promote the growth and development of the body,regulate the function of the body and maintain the metabolism of the human body.Compared with the elements in the form of inorganic salts,metal chelating peptides are more easily absorbed by the human body.Metal chelating peptides efficiently provide various trace elements necessary for life activities,have antioxidant,antibacterial and other biological activities,and have broad application prospects in food,medicine,cosmetics and other fields.In this paper,the methods of preparation,separation and purification of metal chelating peptides from animals and plants were reviewed,the structure-activity relationship and antioxidant activity of metal chelating peptides were analyzed,and the development prospect of metal chelating peptides was prospected.

    Keywords: chelation;peptides;metal;structural characterization;separation and purification;bioavailability

    Background

    Some metal elements,especially trace elements,have obvious nutritional and physiological functions to the human body;and are an indispensable part of human life activities.They maintain a certain concentration in human body fluids and various organs,and are not only part of the human body,but also components of enzymes and vitamins;maintain the pH and electrolytic balance of blood;participate in endocrine,affect gonad development,fertility,sexual function and glucose metabolism;closely related to material transport and energy metabolism [1-4].Their content in the body is too low or too high,it will cause disease,and be harmful to health [5].However,at present,the absorption rate of mineral supplements in the market is not high,and there are side effects such as increasing kidney burden[6-8],so people turn their attention to metal chelating peptides using food-derived peptides as dietary metal carriers [9].

    Metal chelating peptides are formed by the coordination of the N-terminal amino group,C-terminal carboxyl group,amino acid side chain and carbonyl and imide groups with metal ions [10].Peptides containing histidine (His),cysteine (Cys),glutamic acid (Glu) and aspartic acid (Asp) usually have strong metal ion chelating activity and are easy to bind to metal ions such as Ca2+,Fe2+and Zn2+through coordination covalent binding or adsorption binding [11].The prepared chelates have the advantages of high biological titer,fast absorption,and strong nutrition,as well as antioxidant,antibacterial,immunomodulatory,hypolipidemic and hypoglycemic activities.Now in the United States,Western Europe and other developed countries,the metal chelating peptide nutritional supplement industry has become more mature;as a more efficient and safer new supplement,peptide metal ion chelate has a better development prospect.This paper reviews the preparation and absorption mechanism of metal chelating peptides from animals and plants at home and abroad,in order to provide a reference for the future application and further research of metal chelating peptides.

    Preparation and optimization of metal chelating peptides

    At present,the preparation of metal chelating peptides is focused on the preparation of peptides and the chelating process of peptides with metal elements.With the extensive and in-depth study on the comprehensive utilization of food resources,more and more animal and plant raw materials from different sources are being used in the preparation of metal chelating peptides,especially the by-products of food processing.Foong [12] and others use supercritical fluid extraction (SFE) to extract active peptides from rice bran (rice processing by-products) to prepare metal chelating peptides.Peptides extracted from processed fish skeletons (such as cod) have the ability to bind calcium and can be used to prepare peptide calcium chelates[13-15].

    Figure 1 depicts the flow chart for the synthesis of metal chelating peptides.Generally speaking,the first step in the preparation of metal chelating peptide is to extract the peptide (to obtain the carrier of metal chelating peptide).The main methods for preparing metal chelated peptide carriers are solvent extraction,enzymatic hydrolysis,chemical synthesis and so on.Because there are some safety problems such as high cost and chemical residue in solvent extraction and chemical synthesis,enzymatic hydrolysis is mainly used at present.Enzymatic hydrolysis has the advantages of mild conditions,high safety and easy to control the hydrolysis process.Still,Due to the differences in protease digestion sites,the chelating effect of the prepared peptides is often different.At present,the research on enzymatic hydrolysis is mainly focused on the screening of suitable enzymes,the optimization of enzymatic hydrolysis conditions and the improvement of the enzymatic hydrolysis process,in order to obtain peptides with high binding metal activity [16].The condition of enzymatic hydrolysis is the key factor affecting the chelation rate[17].The chelating conditions and the conditions of chemical modification of peptides also have significant effects on the chelation rate and chelate yield.Optimizing these conditions can achieve the purpose of fully using raw materials and maximizing economic benefits.

    The type of protease determines the amino acid sequence of the peptide,which in turn determines the metal ion chelation of the peptide.At present,multi-enzyme combination is often used for simultaneous enzymatic hydrolysis or step-by-step enzymatic hydrolysis,or ultrasonic,microwave-assisted,pulsed electric field and other auxiliary means are used to improve the chelation rate of metal ions.Cui [23] and others use double enzymatic hydrolysis of protein raw materials to prepare bioactive peptides.Compared with single enzymatic hydrolysis,the yield of protein peptides is significantly increased.Ikram [24] studied the effects of ultrasound and heat treatment on the enzymatic hydrolysis of highland barley brewer's spent grain protein hydrolysates (HBSGPH).The results showed that the metal chelating activity of the peptide was enhanced after treatment.Wang et al.[25] used papain,alkaline enzyme and trypsin as raw materials to improve the extraction efficiency of sesame protein by enzymatic reaction of papain (0.5-2 U/mg,pH 7.0,50 ℃),alkaline enzyme (≥2.4 Au/g,pH 8.5,60 ℃) and trypsin (250 U/mg,pH 8.0,55 ℃),respectively.Generally speaking,the degree of protein hydrolysis is greatly affected by raw materials,proteases,enzymatic hydrolysis conditions and other factors,so it is necessary to determine the best protease hydrolysis process for different substrates in order to efficiently prepare bioactive products with the assistance of modern technology.

    Structural characterization and analysis of metal chelating peptide

    The differences in the amino acid sequence and structure of the peptides and the types of metal ions determine the different chelation sites [11].Peptides and metal chelates are two different substances.The common methods to identify chelating groups and analyze the structure and amino acid composition of metal chelating peptides are mass spectrometry (MS),nuclear magnetic resonance (NMR),ultraviolet-visible (UV-vis) absorption spectroscopy,Fourier transform infra-red (FTIR),circular dichroism (CD),X-ray diffraction (XRD) and so on [26].The different structure of metal chelating peptides is bound to affect the function of chelates,so the study of the structure-activity relationship of chelates is of great significance to the development and utilization of metal chelating peptides.

    Molecular size

    It is found that the molecular weight of peptides has a very important effect on the chelation of peptides with metal ions,and some peptides with low molecular weight (<500 Da) have good metal chelating activity [27].The molecular weight first affects its chelating activity,and to a certain extent,the chelating ability is negatively correlated with the molecular weight of peptides.Guo et al.[28] identified the iron chelating peptide from Alaskan cod skin with a molecular weight of only 345 Da;Li et al.[29]found that low molecular weight peptides have higher iron chelating activity than high molecular weight peptides when they study the iron chelating peptides from broad bean protein.Guo et al.[30] extracted small-molecular-weight collagen peptides (CPs) from puffer fish skin,which has higher zinc chelating ability.Xia et al.[31] found that the iron chelating activity of small peptides from barley glutenin whose molecular weight is lower than 1 KDa is stronger.

    Of course,it does not rule out that some polymer peptides also have good metal chelating activity.Miao et al.[32] isolated and identified four iron chelating peptides from casein hydrolysates,named casein hydrolytic peptides CHP-1,CHP-2,CHP-3 and CHP-4 with molecular weights of 830.6120 Da,1012.5280 Da,873.4440 Da and 829.4570 Da,respectively.When Seth and Mahoney [33] studied the binding of iron to chicken protein peptides,they found that most of the iron is bound to macromolecular peptides(>10 kDa),while only about 10%is bound to small peptides and amino acids.

    There are some inconsistencies in these results,partly because of the different sources and structures of peptides,and different binding properties of metal ions,and also because the methods used in different studies are different.Therefore,it is necessary to further explore the effects of different molecular weights on chelating activity.

    Amino acid composition and sequence

    The amino acid composition and sequence of peptides are also important factors affecting their metal chelating activity.Peptides usually containing histidine (His),cysteine (Cys),glutamic acid (Glu)and aspartic acid (Asp) have strong metal ion chelating activity and are easy to bind to metal ions such as Ca2+,Fe2+,Zn2+through coordination covalent binding or adsorption.Some small peptides or special amino acid sequences such as "Asn-Cys-Ser" are considered to have high chelating activity [11].Huang et al.[34] purified from shrimp enzymatic hydrolysate by ion exchange chromatography and Gmur25 dextran gel chromatography,obtained the peptide with the strongest chelating ability to Fe2+,and found that the binding site of Fe2+was glutamic acid (Glu) residue by infrared spectrum analysis.Three novel iron chelating peptides were isolated and purified from Pacific cod skin gelatin by Wu[35].The amino acid sequences provide additional iron binding sites for GPAGPHGPPGKDGR,AGPHGPPGKDGR and AGPAGPAGAR,Lys,His and Asp.Torres-Fuentes et al.[36] found that small peptides containing 20%~30% histidine (His) from chickpea protein had higher copper chelating activity than other components with low histidine.Thus it can be seen that the chelating activity is easier to carry out when the peptide contains cysteine,glycine and histidine.

    Special groups and chelating sites

    By using infrared spectroscopy and nuclear magnetic resonance techniques,it was found that there were some amino acid groups and residues in the chelation process and binding sites between peptides and metal ions,such as carboxyl,carbonyl,sulfhydryl,negative charge and ionic bond can promote metal chelation [37].For example,Wu [34] has isolated and purified three new iron chelating peptide groups from Pacific cod skin gelatin,in which the amino and carboxyl terminal groups and peptide bonds of the peptide skeleton,as well as the amino and imine groups of the arginine side chain are involved in the chelation.The coordination of metal ions with peptides occurs on amino,imino or carboxyl groups and is bonded in the form of monodentate covalent bonds,and it is found that the binding of small peptides to calcium is closely related to the carbonyl groups of peptides [38].The chelating ability of metal chelating peptides containing residues Asp,Glu and His is mainly related to the carboxyl groups on Asp and Glu and imidazolyl groups on His[39].

    When the chelating site was determined,the change of the characteristic absorption peak could reflect the binding of metal ions to the organic coordination groups on the peptide [40].For example,Cui [41] extracted an octapeptide from sea cucumber egg pancreas and spontaneously combined with Ca2+at a stoichiometric ratio of 1:1 to form a peptide calcium chelate.Infrared and Raman spectra show that carboxyl oxygen atoms and amino nitrogen atoms located in Glu and Asp are potential calcium binding sites of sea cucumber polypeptides.

    Phosphorylation is a common chemical modification method,the phosphorylation of peptides will affect the chelation with metal ions,and the chelation rate decreases with the decrease of peptide dephosphorylation level.Phosphorylation treatment can significantly increase the chelation rate when applied to metal chelating peptides[42].Sun [43] and other enzymes hydrolyzed the protein in herring eggs and then phosphorylated with cyclic trisodium phosphate to obtain herring methionine phosphate peptide.Compared with the unphosphorylated peptide,the phosphopeptide had stronger calcium binding ability.It is speculated that the phosphopeptide has more carboxyl and serine phosphate residues that interact with Ca2+.In summary,the chelating sites of peptide calcium chelation reaction are mainly amino group and carboxyl group,and the chelating activity of polypeptide with calcium ion is enhanced after chemical modification.

    19. The woman…began to weep: Nothing about the wife s appearance or demeanor86 suggests that she is monstrous87 herself. On the contrary, her kindness may reflect the loving aspect of the boys own parents, in contrast with their ogre-ish side-the side that would abandon them in the forest.Return to place in story.

    At present,the structural characterization of metal chelates at home and abroad can only determine the chelation between peptides and metal ions,which is limited to the analysis of chelating groups and special amino acids.

    Isolation and purification of metal chelating peptides

    Due to the continuity of the enzymatic hydrolysis process and the non-specificity of protease,the composition of enzymatic hydrolysis products is complex,and the target metal chelating peptides are mixed in the mixture of amino acids and short peptides,which need to be separated and purified.In order to further explore the structure,chelation sites and mechanism of the chelates,Table 1 shows preparation conditions and physiological activity characteristics of metal chelating peptides.Usually ultrafiltration membrane with specific molecular weight interception,immobilized metal ion affinity chromatography (IMAC) and hydroxyapatite chromatography (HAC)were used as the first step to roughly separate the enzymatic hydrolysates,and then further separated by dextran gel chromatography or ion exchange chromatography (IEC).Finally,the components with high purity and activity were obtained by reversed-phase high performance liquid chromatography (RP-HPLC),and their amino acid sequences were identified by mass spectrometry.

    In the first stage of purification of metal chelating peptides,the high selectivity of IMAC makes it a good technology for the purification of proteins and peptides.It can separate peptides with different metal ion chelating abilities and is widely used in peptide separation [53].Wang et al.[51] purified 6 zinc chelating peptides from sesame enzymatic hydrolysate by IMAC and RP-HPLC.Guo et al.[28] successfully isolated and identified iron chelated peptides from the hydrolysate of cod skin by IMAC.

    RP-HPLC is usually used in the final purification stage of metal chelating peptides.The components isolated and purified by RP-HPLC can be used to determine the amino acid composition and peptide structure directly.RP-HPLC is widely used in the separation and purification of metal chelating peptides because of its high separation efficiency,good selectivity and low price of mobile phase [34].Zhang et al.[40] used HAC and RP-HPLC to separate the hydrolysate of cod bone in Taiping Ocean,and obtained Peptide-K,which was identified as KGDPGLSPGK and showed high calcium binding activity.Cai et al.[54] used gel filtration chromatography and RP-HPLC to isolate and purify a new peptide (Phe-Tyr) with specific calcium binding ability from the genus Schizomonas.

    After the enzymatic hydrolysis product was separated and purified to get a single component,the amino acid sequence of the peptide was identified by mass spectrometry.Zhao et al.[55] obtained a calcium binding peptide with molecular weight of 237.99 Da from whey protein hydrolysate by anion exchange chromatography,Sephadex G-25 gel filtration and RP-HPLC.Its amino acid sequence was identified as Gly-Tyr by time-of-flight mass spectrometry (TOF-MS),which was 122% higher than that of the whey protein hydrolysate complex.Jung et al.[56] separated and purified the polypeptide calcium chelate by hydroxyapatite affinity chromatography,and determined its amino acid sequence by electrospray ionization tandem mass spectrometry (ESI-QTOF).It was found that its amino acid sequence was similar to actin.There are many options for the separation and purification of peptides,but there are problems such as too long time,low efficiency,etc.There are many choices for the separation and purification of peptides,but there are some problems such as too long time and low efficiency.From an industrial point of view,it is necessary to develop more efficient technologies and develop and prepare value-added products on a large scale.

    Physiological activity of metal chelating peptides

    Study on bioavailability

    Peptide calcium chelates have good solubility,absorption and stability,and can effectively transport calcium ions through intestinal epithelial cells in a weakly alkaline environment with a pH of 7.2 in the gastrointestinal tract,and are absorbed and utilized by the body.This provides a good basis for application in food production [57].However,when it is put into production as a human mineral supplement,in vitrodigestion experiments,cell experiments and mouse experiments are needed to determine its safety and bioavailability.

    Taking peptide-calcium chelates as an example,the main methods to evaluate the bioavailability of peptide-calcium chelates are cell modelsin vitroand animal experimentsin vivo.Cell experiments can well determine the effect of metal chelates on promoting ion absorption.In vitrocell models include Caco-2 cell model and HT-29 cell model.Caco-2 cells come from human colon cancer cell line,and automatically differentiate into structural characteristics similar to human intestinal epithelial cellsin vitro,and have a similar transport system and functional expression of marker enzymes to small intestinal epithelial cells.HT-29 cell line is often used to study the model of calcium absorptionin vitrobecause of its ability to differentiate into different cell modes.Zhu et al.[58] found that zinc chelate with peptides from wheat germ protein has higher bioavailability of zinc in Caco-2 cells than ZnSO4.Malison A et al.[59]identified a high content of calcium and isolated peptides with strong metal binding ability in the by-products of chicken claw soup.The toxicity and bioavailability of peptide calcium chelates were determined by cell experiments.These results show that peptide calcium chelates play an important role in promoting calcium absorption and transport.

    Animal models are widely used to study bioavailabilityin vivo.Calcium chelated peptides can promote calcium absorption,increase bone mineral density and strength,and reduce the risk of osteoporosis[60].Zhang [40] verified that the calcium binding peptide prepared from Pacific cod bone has anti-osteoporotic activity by establishing the model of osteoporosis in ovariectomized rats.The results show that the chelating peptide can increase the bioavailability of calcium and serum calcium,reduce the bone turnover rate,and improve osteoporosis.

    IDA (iron-deficiency anemia) mouse model was used to study the mechanism of promoting iron absorption in peptide-ferrous ion chelates.Bo et al.[47] prepared peptide-ferrous ion chelates from desalted duck egg albumin peptide.After the application of IDA mouse model,compared with the absorption of ferrous inorganic acid,the chelate significantly increased the body weight of IDA mice and effectively improved the binding ability of transferrin such as hemoglobin (Table 1).

    At present,there has been a more in-depth exploration of the mechanism of metal chelating peptides promoting absorption.It has been found that metal ions must be transformed into organic state with the help of coenzymes after being ingested by the human body.That is,chelates are formed with amino acids or peptides for absorption,transport,storage and utilization [61].Because the body's demand for protein is not a single absorption of free amino acids,small peptides are also a form of absorption and have an independent absorption mechanism with free amino acids in the body [62].After forming organic states with peptides,metal ions have some advantages that inorganic states do not have,such as the stable structure of chelates to avoid the precipitation or adsorption of mineral elements by other nutrients during intestinal absorption.In the chelated state,metal ions are absorbed through the absorption channels of amino acids and peptides rather than metal ions,so as to avoid antagonistic competition with other metal ions absorbed by the same channel and improve the absorption efficiency.Peptide-metal ion chelate is not only the main form of absorbing and transporting metal ions,but also the intermediate in the process of protein synthesis,which can reduce many biochemical processes and save energy consumption [63].

    Generally speaking,metal chelates have higher digestive stability.Compared with inorganic metal element supplements,metal chelates have higher bioavailability and better effect of promoting iron absorption,so they have good application prospects.

    Antioxidant activity

    Metal ions such as copper and iron ionsin vivocontain unpaired electrons.As the main catalyst of Fenton reaction,metal chelating peptides which can bind copper and iron ions can block the production of free radicals and have certain antioxidant activity.By chelating with metal ions,peptides can change the physical position of transition metals and hinder the interaction between metals and lipids and peroxides,thus realizing antioxidation [64].Therefore,metal chelating peptides are also considered to have certain antioxidant activity.As early as 1986,it was found that the copper chelated peptide obtained from chickpea protease hydrolysate had good antioxidant activity and could effectively prevent the oxidation of β-carotene [65].Yuan et al.[66] hydrolyzed Grifola frondosa protein with alkaline protease to obtain hydrolysate,which was chelated with ferrous ions to obtain metal chelate.In vitrostudies showed that peptide iron chelate had good immune enhancement activity on splenocyte proliferation and cytokine secretion,and the iron chelating peptide of Grifola frondosa remained this activity after digestionin vitro.Recently,it has been found that the antioxidant activity of metal chelating peptides is not only related to its ability to chelate metal ions to prevent the formation of free radicals,but also to some of its own active groups.Small peptides that can chelate metals usually contain indolyl,imidazole and sulfhydryl groups derived from tyrosine,histidine and cysteine,which also play an important role in the antioxidation of peptides [67].In a word,the further study on the antioxidant activity of metal chelating peptides will have an important impact on the further development and utilization of metal chelating peptides.

    Antibacterial activity

    Some peptides and metal ions have antibacterial activity themselves.after chelating with metal ions,the antioxidant or antibacterial activity of peptides is generally higher than that of the original peptides,and some peptide calcium chelates and peptide iron chelates have been proved to have antibacterial activity.Studies have confirmed that the antioxidant activity of peptide calcium chelates not precipitated by ethanol is equivalent to 94.43% of tocopherol,while chelates precipitated by 80% ethanol have certain antibacterial activity,such as inhibiting the growth ofBacillus subtilisandStaphylococcus aureus[68].In addition,Ding [69] carried out antimicrobial circle experiments on polypeptide-calcium chelates and found that polypeptide-calcium chelates had certain inhibitory effects onEscherichia coli,Staphylococcus aureus,Pseudomonas fluorescens,Bacillus subtilis,Candida albicans,Saccharomyces cerevisiae,Aspergillus Nigerand so on.

    The antibacterial activity of some metal chelating peptides is close to or even better than some common antimicrobial agents which have been widely used at present,but as one of the raw materials of chelates,peptides come from natural animal and plant proteins,so there is almost no safety problem.Therefore,chelates as antimicrobial agents in food,cosmetics and other industries have great advantages and prospects.

    Discussion and prospect

    For a long time,the bioavailability of inorganic mineral supplements is low,and metal chelating peptides have higher bioavailability and stability than ordinary mineral supplements.At the same time,it has the advantages of fast absorption,and strong nutrition,as well as antioxidant,antibacterial,immunomodulatory,lipid-lowering and hypoglycemic activities.We always think of "the more bioavailable,the more reactive",but metal chelating peptides "protect" metal ions chemically or physically,thus achieving the effect of antioxidation and improving bioavailability;and metal chelating peptides can hinder the interaction between metal ions and dietary components and reduce side effects [70].

    However,from the perspective of food industry standards,in order to consider the impact of the source of metal chelating peptides,it is necessary to further evaluate the bioavailability.Metal chelates obtained from protein hydrolysates can also be used as food ingredients,but the binding force,structure,mineral release and absorption of these chelates,especially food matrix factor,must be studied.At present,metal chelating peptides are not enough to be effectively applied to the food industry.These chelates can only be used as potential applications of food ingredients,and can only be applied to some special populations (For example,peptide iron chelates applied to anaemia population).At present,it is impossible to replace ordinary mineral supplements in the large-scale market of population consumption.

    Generally speaking,metal chelating peptides still have the following problems: (1) In the process of production,people can not study it qualitatively or quantitatively,which makes it difficult to control the quality of metal chelating peptides;(2) There are few studies on its safety evaluation;(3) The efficient separation and purification of chelates need to be improved by 4.5%.In terms of industrial production,at present,the production cost of metal chelating peptides is high and the amount of synthesis is low.So people still tend to buy inorganic salt elements.Therefore,it is necessary to explore the optimal technological conditions of the chelating process,deeply study the chelating mechanism,develop low-cost,high-performance proteins and metal chelating peptides,and solve the problems in practical applications.

    又粗又硬又长又爽又黄的视频| 欧美精品人与动牲交sv欧美| 纵有疾风起免费观看全集完整版| 国产女主播在线喷水免费视频网站| 国产精品一区二区性色av| 日韩欧美 国产精品| 亚洲精品视频女| 蜜臀久久99精品久久宅男| 亚洲精品日韩在线中文字幕| 久久免费观看电影| av网站免费在线观看视频| 性高湖久久久久久久久免费观看| 亚洲美女黄色视频免费看| 自拍欧美九色日韩亚洲蝌蚪91 | 精品久久久噜噜| 国产欧美亚洲国产| 看非洲黑人一级黄片| 精品一区在线观看国产| 在线免费观看不下载黄p国产| 亚洲第一av免费看| 成年美女黄网站色视频大全免费 | 日日爽夜夜爽网站| 男人爽女人下面视频在线观看| 狠狠精品人妻久久久久久综合| 97超碰精品成人国产| 我的老师免费观看完整版| 桃花免费在线播放| 一二三四中文在线观看免费高清| 国产爽快片一区二区三区| 国产毛片在线视频| 免费人妻精品一区二区三区视频| 七月丁香在线播放| 国产精品国产三级国产av玫瑰| 国产精品嫩草影院av在线观看| 91在线精品国自产拍蜜月| 偷拍熟女少妇极品色| 一边亲一边摸免费视频| 免费观看性生交大片5| 视频中文字幕在线观看| 777米奇影视久久| 精品久久国产蜜桃| 一级毛片久久久久久久久女| 啦啦啦视频在线资源免费观看| 国产免费一区二区三区四区乱码| 人妻少妇偷人精品九色| 超碰97精品在线观看| 亚洲精品一区蜜桃| 国产在线男女| 国产精品一区二区在线观看99| 午夜福利网站1000一区二区三区| 国产亚洲5aaaaa淫片| 国产精品福利在线免费观看| 午夜免费鲁丝| 如何舔出高潮| 亚洲成人av在线免费| 搡女人真爽免费视频火全软件| 最近中文字幕高清免费大全6| 国产精品一二三区在线看| 人妻 亚洲 视频| 男的添女的下面高潮视频| 一级片'在线观看视频| 国产精品嫩草影院av在线观看| 99热这里只有是精品50| 91午夜精品亚洲一区二区三区| 国产亚洲欧美精品永久| 麻豆乱淫一区二区| 亚洲久久久国产精品| 亚洲精品久久久久久婷婷小说| 又粗又硬又长又爽又黄的视频| 老司机影院成人| 成人美女网站在线观看视频| 亚洲精品乱码久久久久久按摩| 日韩av免费高清视频| 中文乱码字字幕精品一区二区三区| 一个人免费看片子| 欧美精品一区二区大全| 国产精品一区二区在线不卡| 啦啦啦啦在线视频资源| www.av在线官网国产| 日本av免费视频播放| 18禁在线播放成人免费| 欧美3d第一页| 女性生殖器流出的白浆| 亚洲综合色惰| 男人爽女人下面视频在线观看| 国产淫语在线视频| 精品人妻偷拍中文字幕| 青春草亚洲视频在线观看| 精品久久久精品久久久| 天堂俺去俺来也www色官网| 久久国产亚洲av麻豆专区| 边亲边吃奶的免费视频| 国产精品无大码| 搡女人真爽免费视频火全软件| 成人黄色视频免费在线看| 国产伦精品一区二区三区视频9| 又粗又硬又长又爽又黄的视频| 91久久精品国产一区二区三区| 一二三四中文在线观看免费高清| 水蜜桃什么品种好| 美女视频免费永久观看网站| videos熟女内射| 亚洲欧美成人精品一区二区| 国产熟女欧美一区二区| 国产伦理片在线播放av一区| 色5月婷婷丁香| 国产精品偷伦视频观看了| 欧美性感艳星| 久久精品国产鲁丝片午夜精品| 免费观看av网站的网址| 欧美国产精品一级二级三级 | 国产av码专区亚洲av| 一本色道久久久久久精品综合| 日韩免费高清中文字幕av| 午夜影院在线不卡| 成人毛片a级毛片在线播放| 日本猛色少妇xxxxx猛交久久| 简卡轻食公司| 在线精品无人区一区二区三| 精品久久久久久电影网| 欧美精品亚洲一区二区| 国产伦理片在线播放av一区| 菩萨蛮人人尽说江南好唐韦庄| 亚洲综合精品二区| a级一级毛片免费在线观看| 国产极品天堂在线| 久久国产亚洲av麻豆专区| 日日啪夜夜爽| 亚洲激情五月婷婷啪啪| 日本与韩国留学比较| 99九九线精品视频在线观看视频| 国产在线一区二区三区精| 国产精品久久久久久久电影| 极品人妻少妇av视频| 一二三四中文在线观看免费高清| 极品教师在线视频| 色视频在线一区二区三区| 亚洲精品,欧美精品| 精品酒店卫生间| 在线观看一区二区三区激情| 久久99热6这里只有精品| 欧美丝袜亚洲另类| 99热这里只有是精品在线观看| 国产精品伦人一区二区| 乱码一卡2卡4卡精品| 亚洲在久久综合| 日韩,欧美,国产一区二区三区| 久久99一区二区三区| 国产精品偷伦视频观看了| 国产极品粉嫩免费观看在线 | www.av在线官网国产| 三上悠亚av全集在线观看 | 看免费成人av毛片| 国产色爽女视频免费观看| 日韩一区二区三区影片| 人妻人人澡人人爽人人| 国产精品免费大片| 精品久久久久久久久亚洲| 久久人妻熟女aⅴ| 一级毛片黄色毛片免费观看视频| 成年美女黄网站色视频大全免费 | 国产色婷婷99| 日韩欧美一区视频在线观看 | 亚洲欧洲日产国产| 中国国产av一级| 成人国产麻豆网| 美女国产视频在线观看| 久久国产乱子免费精品| 日本色播在线视频| 国产欧美亚洲国产| av黄色大香蕉| 免费观看无遮挡的男女| 久久99一区二区三区| 性高湖久久久久久久久免费观看| 成人亚洲欧美一区二区av| 日韩一本色道免费dvd| 亚洲精品久久久久久婷婷小说| 国产精品成人在线| 国产精品国产三级国产av玫瑰| 天堂8中文在线网| 亚洲精品第二区| 日本欧美视频一区| 伦精品一区二区三区| 大话2 男鬼变身卡| 亚洲欧美成人综合另类久久久| 又粗又硬又长又爽又黄的视频| 亚洲精品国产成人久久av| 高清av免费在线| 国产一区二区在线观看日韩| 99热国产这里只有精品6| 中国三级夫妇交换| 成人国产麻豆网| 天天躁夜夜躁狠狠久久av| 人人妻人人澡人人爽人人夜夜| 在线看a的网站| 国内少妇人妻偷人精品xxx网站| 又大又黄又爽视频免费| 久久人人爽av亚洲精品天堂| 中文字幕av电影在线播放| 亚洲欧美日韩卡通动漫| 男人和女人高潮做爰伦理| 中文字幕亚洲精品专区| 日日摸夜夜添夜夜添av毛片| 天堂中文最新版在线下载| 亚洲精品亚洲一区二区| 18+在线观看网站| 亚洲欧美日韩另类电影网站| 中文字幕亚洲精品专区| 日韩电影二区| 黄色欧美视频在线观看| 久久久久国产网址| 男人舔奶头视频| 精品久久久久久电影网| 狂野欧美激情性xxxx在线观看| 女人精品久久久久毛片| 亚洲av福利一区| 9色porny在线观看| 一级二级三级毛片免费看| 成年av动漫网址| 天堂中文最新版在线下载| 国产高清国产精品国产三级| 涩涩av久久男人的天堂| av播播在线观看一区| 少妇猛男粗大的猛烈进出视频| 99热这里只有是精品50| 国内揄拍国产精品人妻在线| 少妇 在线观看| 国产白丝娇喘喷水9色精品| 午夜激情久久久久久久| 日日啪夜夜爽| 国产一区二区三区av在线| 噜噜噜噜噜久久久久久91| 久久综合国产亚洲精品| 国产免费视频播放在线视频| 久久97久久精品| 日韩免费高清中文字幕av| 校园人妻丝袜中文字幕| 国产 精品1| 韩国高清视频一区二区三区| 国产69精品久久久久777片| 热re99久久精品国产66热6| 亚洲av成人精品一区久久| 国产精品99久久久久久久久| 精品国产露脸久久av麻豆| 欧美日韩视频精品一区| 多毛熟女@视频| 青春草国产在线视频| 色网站视频免费| av天堂久久9| 国产乱人偷精品视频| 永久免费av网站大全| 精品国产露脸久久av麻豆| 成人漫画全彩无遮挡| 亚洲精品一区蜜桃| 如日韩欧美国产精品一区二区三区 | 亚洲国产日韩一区二区| 国产精品欧美亚洲77777| 久久久久久人妻| 天天操日日干夜夜撸| 亚洲精品久久午夜乱码| 久久久精品免费免费高清| 日韩伦理黄色片| 欧美日韩av久久| 国产精品一区二区在线观看99| 男女边吃奶边做爰视频| 久久久a久久爽久久v久久| 欧美日韩视频精品一区| 99热全是精品| 成人毛片a级毛片在线播放| 少妇猛男粗大的猛烈进出视频| 欧美变态另类bdsm刘玥| 成人国产av品久久久| 国产日韩欧美亚洲二区| 亚洲精品日韩av片在线观看| 国产精品一二三区在线看| 精品熟女少妇av免费看| 亚洲色图综合在线观看| 亚洲国产精品999| 自拍欧美九色日韩亚洲蝌蚪91 | 亚洲av.av天堂| 中文字幕精品免费在线观看视频 | 在线观看美女被高潮喷水网站| 欧美成人精品欧美一级黄| 麻豆成人av视频| 国产亚洲一区二区精品| 丝袜喷水一区| 男的添女的下面高潮视频| a级毛片免费高清观看在线播放| 国产视频内射| 不卡视频在线观看欧美| 婷婷色麻豆天堂久久| 久久久久人妻精品一区果冻| 纯流量卡能插随身wifi吗| 最近中文字幕2019免费版| 九九久久精品国产亚洲av麻豆| 亚洲情色 制服丝袜| 男人狂女人下面高潮的视频| 不卡视频在线观看欧美| 国产一区二区在线观看av| 免费观看的影片在线观看| 内射极品少妇av片p| 最新中文字幕久久久久| 亚洲成人一二三区av| 尾随美女入室| 插逼视频在线观看| 毛片一级片免费看久久久久| 亚洲国产日韩一区二区| 免费观看性生交大片5| 亚洲人成网站在线观看播放| 免费久久久久久久精品成人欧美视频 | 欧美精品一区二区大全| 亚洲精品日本国产第一区| 在线天堂最新版资源| 美女福利国产在线| 国产成人一区二区在线| 国产极品粉嫩免费观看在线 | 国国产精品蜜臀av免费| 中文精品一卡2卡3卡4更新| 亚洲国产精品成人久久小说| 国产成人一区二区在线| 99久久精品热视频| 色视频在线一区二区三区| 18禁动态无遮挡网站| 久久久久久久久久久免费av| 国产男人的电影天堂91| 日本黄色片子视频| 亚洲成色77777| 在线观看三级黄色| 99热这里只有是精品在线观看| 久久精品国产亚洲av涩爱| 菩萨蛮人人尽说江南好唐韦庄| 秋霞在线观看毛片| 老司机影院毛片| 美女xxoo啪啪120秒动态图| 97在线人人人人妻| 蜜臀久久99精品久久宅男| 春色校园在线视频观看| av视频免费观看在线观看| 欧美精品一区二区免费开放| 91精品伊人久久大香线蕉| 中文字幕久久专区| 国产 一区精品| 日韩欧美精品免费久久| 午夜免费男女啪啪视频观看| 精品一区二区免费观看| 午夜精品国产一区二区电影| 少妇人妻一区二区三区视频| 亚洲av综合色区一区| 亚洲av国产av综合av卡| 国产中年淑女户外野战色| 欧美三级亚洲精品| 在线 av 中文字幕| 日本-黄色视频高清免费观看| 国产成人a∨麻豆精品| 国产在线免费精品| 大片免费播放器 马上看| 三级经典国产精品| 热re99久久国产66热| 内射极品少妇av片p| 亚洲情色 制服丝袜| 中文资源天堂在线| 9色porny在线观看| 在线精品无人区一区二区三| 精品少妇久久久久久888优播| 色5月婷婷丁香| 久久久精品94久久精品| 另类亚洲欧美激情| 精品一区在线观看国产| 少妇的逼水好多| 伦理电影免费视频| 18+在线观看网站| 日韩强制内射视频| 国产又色又爽无遮挡免| 国产综合精华液| 国产探花极品一区二区| 久久青草综合色| 少妇的逼水好多| 亚洲精品国产成人久久av| 欧美变态另类bdsm刘玥| 欧美性感艳星| 伊人久久精品亚洲午夜| 美女福利国产在线| 九九在线视频观看精品| 日韩亚洲欧美综合| 亚洲精品乱码久久久久久按摩| a 毛片基地| a级毛片在线看网站| 丝袜脚勾引网站| 日韩人妻高清精品专区| 建设人人有责人人尽责人人享有的| 欧美精品人与动牲交sv欧美| 日韩一区二区三区影片| 免费观看a级毛片全部| 国产精品伦人一区二区| 日韩不卡一区二区三区视频在线| 国产爽快片一区二区三区| 99久久精品热视频| 国产成人精品一,二区| 亚州av有码| 国产一区有黄有色的免费视频| xxx大片免费视频| 一级爰片在线观看| 欧美国产精品一级二级三级 | 亚洲情色 制服丝袜| 99国产精品免费福利视频| 青青草视频在线视频观看| 亚洲在久久综合| 亚洲色图综合在线观看| 最近中文字幕2019免费版| 美女cb高潮喷水在线观看| av.在线天堂| 亚洲精品日本国产第一区| av网站免费在线观看视频| 丝袜脚勾引网站| 亚洲精品日韩在线中文字幕| 国产精品国产三级国产专区5o| 国产黄频视频在线观看| 国产精品久久久久久久久免| 日本午夜av视频| 亚洲国产成人一精品久久久| 色吧在线观看| 免费人成在线观看视频色| 少妇的逼好多水| 久久这里有精品视频免费| 国产精品欧美亚洲77777| 97超碰精品成人国产| 国产亚洲最大av| 熟女av电影| 天堂8中文在线网| 免费大片黄手机在线观看| 大片免费播放器 马上看| 精品国产露脸久久av麻豆| 五月天丁香电影| 男女啪啪激烈高潮av片| 天堂俺去俺来也www色官网| 欧美日韩视频精品一区| 亚洲国产精品国产精品| 亚洲精品色激情综合| 午夜免费观看性视频| 97在线视频观看| 欧美人与善性xxx| 啦啦啦中文免费视频观看日本| www.av在线官网国产| 国模一区二区三区四区视频| 交换朋友夫妻互换小说| 日韩一区二区三区影片| 视频区图区小说| 97在线人人人人妻| 有码 亚洲区| 亚洲无线观看免费| 日日摸夜夜添夜夜爱| 国产精品久久久久久久电影| 国产av国产精品国产| 免费人妻精品一区二区三区视频| 久久精品久久精品一区二区三区| 久久久久久久亚洲中文字幕| 国产成人免费观看mmmm| 中文字幕人妻熟人妻熟丝袜美| 国产精品成人在线| 久久精品久久久久久久性| 国产精品福利在线免费观看| av女优亚洲男人天堂| 国产有黄有色有爽视频| 婷婷色综合www| 亚洲成色77777| 嫩草影院新地址| 中国美白少妇内射xxxbb| 99九九线精品视频在线观看视频| av视频免费观看在线观看| 久久久精品94久久精品| 人人妻人人看人人澡| 有码 亚洲区| 一级毛片aaaaaa免费看小| 国产精品秋霞免费鲁丝片| av在线app专区| 国产成人免费观看mmmm| 91成人精品电影| 大码成人一级视频| 少妇精品久久久久久久| 精品久久久久久电影网| 久久精品国产a三级三级三级| 日韩伦理黄色片| 99热全是精品| 两个人的视频大全免费| 高清欧美精品videossex| 成人亚洲欧美一区二区av| 亚洲精品第二区| 亚洲精品自拍成人| 国产淫片久久久久久久久| 色网站视频免费| 美女内射精品一级片tv| 成人免费观看视频高清| 一二三四中文在线观看免费高清| 日韩精品免费视频一区二区三区 | 一区在线观看完整版| 久久97久久精品| 一级毛片aaaaaa免费看小| 七月丁香在线播放| 久热久热在线精品观看| 久久99蜜桃精品久久| 国产一级毛片在线| 亚洲欧洲国产日韩| 国内精品宾馆在线| 日本黄大片高清| 亚洲精品国产av成人精品| 欧美日韩一区二区视频在线观看视频在线| 一级毛片我不卡| 黄色日韩在线| 最后的刺客免费高清国语| 亚洲av二区三区四区| 亚洲精品国产色婷婷电影| 另类亚洲欧美激情| 精品午夜福利在线看| 亚洲av成人精品一区久久| 我的女老师完整版在线观看| 国产日韩欧美亚洲二区| 一级毛片 在线播放| 欧美成人午夜免费资源| 日韩中字成人| 女的被弄到高潮叫床怎么办| 免费观看a级毛片全部| 亚洲精品456在线播放app| 如日韩欧美国产精品一区二区三区 | av网站免费在线观看视频| 亚洲国产色片| 在线观看一区二区三区激情| 男女边摸边吃奶| 精品人妻熟女av久视频| 久久人妻熟女aⅴ| 精品少妇内射三级| 一个人看视频在线观看www免费| 人人妻人人添人人爽欧美一区卜| 色5月婷婷丁香| 国产综合精华液| 亚洲欧美日韩东京热| 日韩成人av中文字幕在线观看| a级片在线免费高清观看视频| √禁漫天堂资源中文www| 亚洲三级黄色毛片| 黑人猛操日本美女一级片| 亚洲精华国产精华液的使用体验| 久久ye,这里只有精品| 久久毛片免费看一区二区三区| a级毛片免费高清观看在线播放| 少妇的逼水好多| 亚洲av电影在线观看一区二区三区| 亚洲欧美成人精品一区二区| 国产精品一区二区在线不卡| 在线播放无遮挡| 久久6这里有精品| 色网站视频免费| 女性被躁到高潮视频| 亚洲精品视频女| 亚洲av在线观看美女高潮| 有码 亚洲区| 大香蕉久久网| 午夜激情福利司机影院| 欧美bdsm另类| 免费人成在线观看视频色| 91精品国产国语对白视频| 91久久精品电影网| 99久久人妻综合| 男女国产视频网站| h日本视频在线播放| 最近2019中文字幕mv第一页| 亚洲欧美成人综合另类久久久| 另类亚洲欧美激情| 最近手机中文字幕大全| 中文欧美无线码| 男人添女人高潮全过程视频| 91精品伊人久久大香线蕉| 亚洲精品久久久久久婷婷小说| 97在线人人人人妻| 少妇裸体淫交视频免费看高清| 久久人妻熟女aⅴ| 久久久久久久大尺度免费视频| 一级片'在线观看视频| 国产白丝娇喘喷水9色精品| 少妇熟女欧美另类| 我的女老师完整版在线观看| 不卡视频在线观看欧美| 国产精品99久久99久久久不卡 | 久久久久人妻精品一区果冻| 免费观看av网站的网址| 中文字幕亚洲精品专区| 91久久精品国产一区二区三区| 亚洲成人av在线免费| 久久99热6这里只有精品| 中文精品一卡2卡3卡4更新| 国产黄片美女视频| 久久久久精品性色| 欧美日韩在线观看h| 久热久热在线精品观看| 国产成人免费观看mmmm| 国产欧美日韩精品一区二区| 伦理电影免费视频| 99re6热这里在线精品视频| 精品国产国语对白av| 高清黄色对白视频在线免费看 | 亚洲精品久久久久久婷婷小说| 中文字幕制服av| 爱豆传媒免费全集在线观看| 久久婷婷青草| 最近中文字幕高清免费大全6| 色94色欧美一区二区| 日韩亚洲欧美综合| 一区二区三区精品91| 久久精品国产a三级三级三级| 国产伦精品一区二区三区视频9| 国产日韩欧美在线精品| 一级二级三级毛片免费看| av福利片在线观看| av女优亚洲男人天堂| 欧美日韩在线观看h| 乱码一卡2卡4卡精品|