I. Intshayelelo
Iiphospholipids ludidi lweelipids eziyinxalenye ebalulekileyo yenwebu zeseli. Isakhiwo sabo esiyingqayizivele, esinentloko ye-hydrophilic kunye nemisila emibini ye-hydrophobic, ivumela i-phospholipids ukuba yenze isakhiwo se-bilayer, sisebenza njengesithintelo esahlula izinto zangaphakathi zeseli ukusuka kwindawo yangaphandle. Le ndima yesakhiwo ibalulekile ekugcineni ingqibelelo kunye nokusebenza kweeseli kuzo zonke izinto eziphilayo.
Ukubonakaliswa kweeseli kunye nonxibelelwano ziinkqubo ezibalulekileyo ezenza ukuba iiseli zikwazi ukusebenzisana kunye kunye nendawo yazo, zivumela iimpendulo ezilungelelanisiweyo kwiintlobo ezahlukeneyo ze-stimuli. Iiseli zinokulawula ukukhula, ukukhula, kunye nemisebenzi emininzi yefiziyoloji ngezi nkqubo. Iindlela zokubonisa iiseli zibandakanya ukuhanjiswa kweempawu, ezinje ngehomoni okanye i-neurotransmitters, ezichongiwe ngama-receptors kwi-membrane yeseli, ezibangela i-cascade yeziganeko ezikhokelela ekugqibeleni kwimpendulo ethile yeselula.
Ukuqonda indima ye-phospholipids ekubonakalisweni kweeseli kunye nonxibelelwano kubalulekile ekuvezeni ubunzima bendlela iiseli ezinxibelelana ngayo kunye nokulungelelanisa imisebenzi yazo. Oku kuqonda kuneziphumo ezifikelela kude kwiinkalo ezahlukeneyo, kubandakanya i-cell biology, i-pharmacology, kunye nophuhliso lonyango olujoliswe kuyo kwizifo ezininzi kunye nokuphazamiseka. Ngokuphonononga kunxibelelwano oluntsonkothileyo phakathi kwe-phospholipids kunye nokubonakaliswa kweeseli, sinokufumana ukuqonda kwiinkqubo ezisisiseko ezilawula ukuziphatha kunye nomsebenzi weselula.
II. Ubume bePhospholipids
A. Inkcazelo yoLwakhiwo lwePhospholipid:
I-Phospholipids zi-amphipathic molecules, oku kuthetha ukuba zineendawo zombini ze-hydrophilic (ezikhanga amanzi) kunye ne-hydrophobic (i-water-repelling). Isakhiwo esisisiseko se-phospholipid siqukethe i-molecule ye-glycerol eboshwe kwiintambo ezimbini ze-fatty acid kunye neqela lentloko equkethe i-phosphate. Imisila ye-hydrophobic, ehlanganiswe ngamaketanga e-fatty acid, yenza i-interior ye-lipid bilayer, ngelixa amaqela eentloko ze-hydrophilic asebenzisana namanzi kwindawo yangaphakathi nangaphandle ye-membrane. Olu lungiselelo olukhethekileyo luvumela i-phospholipids ukuba ihlangane ngokwayo kwi-bilayer, kunye nemisila ye-hydrophobic ejoliswe ngaphakathi kunye neentloko ze-hydrophilic ezijongene neendawo ezinamanzi ngaphakathi nangaphandle kweseli.
B. Indima yePhospholipid Bilayer kwiCell Membrane:
I-phospholipid bilayer licandelo elibalulekileyo lesakhiwo senwebu yeseli, ibonelela ngomqobo ongemi-permeable olawula ukuhamba kwezinto ukungena nokuphuma kwiseli. Oku kutyunjwa okukhethiweyo kubalulekile ekugcineni indawo yangaphakathi yeseli kwaye kubalulekile kwiinkqubo ezifana nokuthatha izondlo, ukukhutshwa kwenkunkuma, kunye nokukhuselwa kwii-arhente ezinobungozi. Ngaphandle kwendima yayo yolwakhiwo, i-phospholipid bilayer ikwadlala indima ebalulekileyo ekubonakalisweni kweeseli kunye nonxibelelwano.
Imodeli ye-mosaic ye-fluid ye-membrane yeseli, ecetywayo nguSinger noNicolson ngo-1972, igxininisa indalo eguquguqukayo kunye ne-heterogeneous ye-membrane, kunye ne-phospholipids eqhubekayo kunye neeprotheni ezahlukeneyo ezithe saa kwi-lipid bilayer. Olu lwakhiwo oluguquguqukayo luyisiseko ekuququzeleleni ukubonakaliswa kweeseli kunye nonxibelelwano. I-receptors, iziteshi ze-ion, kunye nezinye iiprotheyini zokubonisa zifakwe ngaphakathi kwe-phospholipid bilayer kwaye ziyimfuneko ekuqapheliseni iimpawu zangaphandle kunye nokuzithumela ngaphakathi kweseli.
Ngaphezu koko, iipropathi ezibonakalayo ze-phospholipids, ezifana ne-fluidity yazo kunye nokukwazi ukwenza i-lipid rafts, zinefuthe kwintlangano kunye nokusebenza kweeprotheni ze-membrane ezibandakanyekayo ekubonakalisweni kweeseli. Ukuziphatha okuguquguqukayo kwe-phospholipids kuchaphazela indawo kunye nomsebenzi wokubonisa iiprotheni, ngaloo ndlela kuchaphazela ukuchaneka kunye nokusebenza kakuhle kweendlela zokubonisa.
Ukuqonda ubudlelwane phakathi kwe-phospholipids kunye nesakhiwo se-membrane yeseli kunye nomsebenzi kunempembelelo enzulu kwiinkqubo ezininzi zebhayoloji, kubandakanya i-homeostasis yeselula, uphuhliso kunye nesifo. Ukudityaniswa kwe-phospholipid biology kunye nophando lokubonisa iiseli luyaqhubeka nokutyhila ukuqonda okubalulekileyo kwiindlela ezintsonkothileyo zokunxibelelana kweeseli kwaye kubambe isithembiso sokuphuhliswa kwezicwangciso zonyango ezitsha.
III. Indima ye-Phospholipids kwi-Cell Signaling
A. Phospholipids njengeeMolekyu zoMqondiso
Iiphospholipids, njengezona nxalenye zibalaseleyo zeemembrane zeseli, ziye zavela njengeemolekyuli zomqondiso ezibalulekileyo kunxibelelwano lweeseli. Amaqela entloko ye-hydrophilic ye-phospholipids, ngakumbi ezo zine-inositol phosphates, zisebenza njengezithunywa zesibini ezibalulekileyo kwiindlela ezahlukeneyo zokubonisa. Ngokomzekelo, i-phosphatidylinositol 4,5-bisphosphate (PIP2) isebenza njengemolekyuli yokubonisa ngokucandwa kwi-inositol trisphosphate (IP3) kunye ne-diacylglycerol (DAG) ekuphenduleni i-extracellular stimuli. Ezi molekyuli ze-lipid zidlala indima ebalulekileyo ekulawuleni amanqanaba e-intracellular calcium kunye nokusebenza kweprotheyini kinase C, ngaloo ndlela imodareyitha iinkqubo ezahlukeneyo zeselula ezibandakanya ukwanda kweeseli, ukwahlula kunye nokufuduka.
Ngaphezu koko, i-phospholipids efana ne-phosphatidic acid (PA) kunye ne-lysophospholipids ziye zaqatshelwa njengeemolekyuli zokubonisa ezichaphazela ngokuthe ngqo iimpendulo zeselula ngokusebenzisana neethagethi ezithile zeprotheni. Ngokomzekelo, i-PA isebenza njengomlamli oyintloko ekukhuleni kweeseli kunye nokwanda ngokusebenza kweeprotheyini zokubonisa, ngelixa i-lysophosphatidic acid (LPA) ibandakanyeka kulawulo lwe-cytoskeletal dynamics, ukusinda kweeseli kunye nokufuduka. Ezi ndima zahlukeneyo ze-phospholipids zibalaselisa ukubaluleka kwazo kwi-orchestrating entsonkothileyo yokubonisa i-cascades ngaphakathi kweeseli.
B. Ukubandakanywa kwePhospholipids kwiiNdlela zoTshintsho lweSignali
Ukubandakanyeka kwe-phospholipids kwiindlela zokuhambisa umqondiso kubonakaliswa ngendima yabo ebalulekileyo ekumodareyitheni umsebenzi we-membrane-bound receptors, ngakumbi i-G protein-coupled receptors (GPCRs). Kwi-ligand ebopha i-GPCRs, i-phospholipase C (PLC) iyasebenza, ekhokelela kwi-hydrolysis ye-PIP2 kunye nesizukulwana se-IP3 kunye ne-DAG. I-IP3 ibangela ukukhululwa kwe-calcium kwiivenkile ze-intracellular, ngelixa i-DAG ivuselela i-protein kinase C, ekugqibeleni ifikelele ekulawuleni i-gene expression, ukukhula kweeseli kunye nokuhanjiswa kwe-synaptic.
Ngaphezu koko, i-phosphoinositides, iklasi ye-phospholipids, isebenza njengeendawo zokumisa iiprotheyini ezibandakanyekayo kwiindlela ezahlukeneyo, kubandakanywa nezo zilawula ukuthengiswa kwe-membrane kunye ne-actin cytoskeleton dynamics. Ukunxibelelana okuguquguqukayo phakathi kwe-phosphoinositides kunye neeprotheyini zabo ezisebenzisanayo zenza igalelo kulawulo lwendawo kunye nexesha lexesha lokubonisa iziganeko, ngaloo ndlela kubumba iimpendulo zeselula kwi-extracellular stimuli.
Ukubandakanyeka kwezinto ezininzi ze-phospholipids kwi-cell signaling kunye neendlela zokuhambisa umqondiso kugxininisa ukubaluleka kwazo njengabalawuli abaphambili be-homeostasis yeselula kunye nomsebenzi.
IV. Phospholipids kunye noNxibelelwano lwe-Intracellular
A. Phospholipids kwi-Intracellular Signaling
I-Phospholipids, iklasi ye-lipids equkethe iqela le-phosphate, idlala indima ebalulekileyo kwi-intracellular signaling, i-orchestrating iinkqubo ezahlukeneyo zeselula ngokubandakanyeka kwazo ekuboniseni i-cascades. Omnye umzekelo obalaseleyo yi-phosphatidylinositol 4,5-bisphosphate (PIP2), i-phospholipid efumaneka kwi-membrane ye-plasma. Ukuphendula kwi-extracellular stimuli, i-PIP2 ixutywe kwi-inositol trisphosphate (IP3) kunye ne-diacylglycerol (DAG) nge-enzyme phospholipase C (PLC). I-IP3 ibangela ukukhululwa kwe-calcium kwiivenkile ze-intracellular, ngelixa i-DAG ivuselela i-protein kinase C, ekugqibeleni ilawula imisebenzi eyahlukeneyo yeselula efana nokunyuka kweeseli, ukuhlukana, kunye nokuhlelwa kwakhona kwe-cytoskeletal.
Ukongezelela, ezinye i-phospholipids, kuquka i-phosphatidic acid (PA) kunye ne-lysophospholipids, ziye zachongwa njengento ebalulekileyo kwi-intracellular signaling. I-PA inegalelo ekulawuleni ukukhula kweeseli kunye nokwanda ngokusebenza njenge-activator yeeprotheni ezahlukeneyo zokubonisa. I-Lysophosphatidic acid (LPA) iye yaqatshelwa ngokubandakanyeka kwayo ekuguquleni ukusinda kweeseli, ukufuduka, kunye ne-cytoskeletal dynamics. Ezi ziphumo zigxininisa iindima ezahlukeneyo kunye nezibalulekileyo ze-phospholipids njengeemolekyuli zokubonisa ngaphakathi kwiseli.
B. Ukusebenzisana kwe-Phospholipids kunye neeProtheyini kunye ne-Receptors
I-Phospholipids iphinda idibane neeprotheni ezahlukeneyo kunye ne-receptors ukulungelelanisa iindlela zokubonisa iselula. Ngokucacileyo, i-phosphoinositides, i-subgroup ye-phospholipids, isebenza njengamaqonga okugaya kunye nokusebenza kweeprotheni zomqondiso. Ngokomzekelo, i-phosphatidylinositol 3,4,5-trisphosphate (PIP3) isebenza njengomlawuli obalulekileyo wokukhula kweeseli kunye nokwanda ngokugaya iiprotheni eziqulethe i-pleckstrin homology (PH) kwi-membrane ye-plasma, ngaloo ndlela iqalisa iziganeko zokubonisa ezantsi. Ngaphezu koko, umbutho oguquguqukayo we-phospholipids kunye neeprotheyini zokubonisa kunye ne-receptors ivumela ulawulo oluchanekileyo lwe-spatiotemporal yeziganeko zomqondiso ngaphakathi kweseli.
Ukusebenzisana kwezinto ezininzi ze-phospholipids kunye neeprotheni kunye ne-receptors zigxininisa indima yazo ebalulekileyo ekuguqulweni kweendlela ze-intracellular signaling, ekugqibeleni zibe negalelo kulawulo lwemisebenzi yeselula.
V. Ukulawulwa kwe-Phospholipids kwi-Cell Signaling
A. I-Enzymes kunye neendlela ezibandakanyekayo kwi-Phospholipid Metabolism
I-Phospholipids ilawulwa ngamandla ngokusebenzisa inethiwekhi eyinkimbinkimbi ye-enzymes kunye neendlela, ezichaphazela ubuninzi babo kunye nomsebenzi ekubonakalisweni kweeseli. Enye indlela enjalo ibandakanya ukuhlanganiswa kunye nokuguqulwa kwe-phosphatidylinositol (PI) kunye ne-phosphorylated derivatives, eyaziwa ngokuba yi-phosphoinositides. I-Phosphatidylinositol i-4-kinases kunye ne-phosphatidylinositol i-4-phosphate i-5-kinases yi-enzymes eyenza i-phosphorylation ye-PI kwiindawo ze-D4 kunye ne-D5, i-phosphatidylinositol 4-phosphate (PI4P) kunye ne-phosphatidy4linosi-phosphate (i-IP) kunye ne-phosphatidy4linosi-2 (P. Ngakolunye uhlangothi, i-phosphatases, njenge-phosphatase kunye ne-tensin homolog (PTEN), i-dephosphorylate phosphoinositides, ukulawula amanqanaba abo kunye nefuthe kwimpawu zeselula.
Ngaphezu koko, i-de novo synthesis ye-phospholipids, ngokukodwa i-phosphatidic acid (PA), ixutywe ngama-enzymes afana ne-phospholipase D kunye ne-diacylglycerol kinase, ngelixa ukuchithwa kwabo kubangelwa yi-phospholipases, kubandakanywa i-phospholipase A2 kunye ne-phospholipase C. Le misebenzi ye-enzymatic yokulawula ngokuhlangeneyo i-theory. i-bioactive lipid mediators, echaphazela iinkqubo ezahlukeneyo zokubonisa iiseli kunye negalelo ekugcinweni kwe-homeostasis yeselula.
B. Impembelelo yoLawulo lwePhospholipid kwiiNkqubo zokuSawula iiSeli
Ulawulo lwe-phospholipids luneziphumo ezinzulu kwiinkqubo zokubonisa iiseli ngokumodareyitha imisebenzi yeemolekyuli ezibalulekileyo zokubonisa kunye neendlela. Ngokomzekelo, ukuguqulwa kwe-PIP2 nge-phospholipase C ivelisa i-inositol trisphosphate (IP3) kunye ne-diacylglycerol (DAG), ekhokelela ekukhululweni kwe-intracellular calcium kunye nokusebenza kweprotein kinase C, ngokulandelanayo. Le miqondiso ye-cascade inefuthe kwiimpendulo zeselula ezifana ne-neurotransmission, contraction muscle, kunye nokusebenza kweeseli zomzimba.
Ngaphezu koko, utshintsho kumanqanaba e-phosphoinositides luchaphazela ukufunwa kunye nokusebenza kweeprotheni ezisebenzayo eziqulethe i-lipid-binding domains, iinkqubo ezichaphazelayo ezifana ne-endocytosis, i-cytoskeletal dynamics, kunye nokufuduka kweeseli. Ukongeza, ukulawulwa kwamanqanaba e-PA ngama-phospholipases kunye ne-phosphatases kuchaphazela ukuthengiswa kwe-membrane, ukukhula kweeseli, kunye neendlela zokubonisa i-lipid.
Ukunxibelelana phakathi kwe-phospholipid metabolism kunye nokubonakaliswa kweeseli kugxininisa ukubaluleka kokulawulwa kwe-phospholipid ekugcineni umsebenzi weselula kunye nokuphendula kwi-extracellular stimuli.
VI. Ukuqukumbela
A. Isishwankathelo seendima eziphambili zePhospholipids kwiSibonakaliso seSeli kunye noNxibelelwano
Isishwankathelo, i-phospholipids idlala indima ebalulekileyo kwi-orchestrating cell signaling kunye neenkqubo zonxibelelwano ngaphakathi kweenkqubo zebhayoloji. Ukwahluka kwabo kolwakhiwo kunye nokusebenza kubenza bakwazi ukusebenza njengabalawuli abaguquguqukayo beempendulo zeselula, kunye neendima eziphambili ezibandakanya:
Umbutho weMembrane:
I-phospholipids zenza iibhloko ezisisiseko ze-membrane zeselula, ukuseka isakhelo sesakhiwo sokwahlulwa kwamacandelo eeseli kunye nokufumaneka kweeprotheyini zengingqi. Ukukwazi kwabo ukuvelisa i-lipid microdomains, ezifana ne-lipid rafts, kuchaphazela intlangano yendawo yokubonisa iimpawu kunye nokusebenzisana kwazo, okuchaphazela ukubonakaliswa kweempawu kunye nokusebenza kakuhle.
Uguqulo loMqondiso:
I-Phospholipids isebenza njengabalamli abaphambili ekugqithiseni izibonakaliso ze-extracellular kwiimpendulo ze-intracellular. I-Phosphoinositides isebenza njengeemolekyuli zokubonisa, ukumodareyitha imisebenzi yeeprotheyini ezisebenzayo ezahlukeneyo, ngelixa i-fatty acids yamahhala kunye ne-lysophospholipids isebenza njengezithunywa zesibini, ezichaphazela ukusebenza kwe-cascades kunye ne-gene expression.
UkuModareyithwa koMqondiso weSeli:
I-Phospholipids inegalelo kulawulo lweendlela ezahlukeneyo zokubonisa, ukulawula iinkqubo ezifana nokwanda kweeseli, ukwahlula, i-apoptosis, kunye neempendulo ze-immune. Ukubandakanyeka kwabo ekuveliseni i-bioactive lipid mediators, kubandakanywa i-eicosanoids kunye ne-sphingolipids, ibonisa ngakumbi impembelelo yabo kwi-inflammation, i-metabolic, kunye ne-apoptotic networking signaling networks.
Unxibelelwano lwe-Intercellular:
I-Phospholipids nayo ithatha inxaxheba ekunxibelelaneni kwe-intercellular ngokukhululwa kwe-lipid mediators, njenge-prostaglandins kunye ne-leukotrienes, elawula imisebenzi yeeseli ezikufutshane kunye nezicubu, ukulawula ukuvuvukala, ukuqonda intlungu, kunye nomsebenzi we-vascular.
Amagalelo ahlukeneyo e-phospholipids kwisignali yeeseli kunye nonxibelelwano lugxininisa ukubaluleka kwabo ekugcineni i-homeostasis yeselula kunye nokulungelelaniswa kweempendulo ze-physiological.
B. Izikhokelo zexesha elizayo zoPhando kwi-Phospholipids kwi-Cellular Signaling
Njengoko iindima ezintsonkothileyo ze-phospholipids ekubonakalisweni kweeseli ziqhubeka nokutyhilwa, iindlela ezininzi ezinomdla zophando lwexesha elizayo ziyavela, kubandakanya:
IiNdlela zeNtsebenziswano:
Ukudityaniswa kweendlela eziphambili zokuhlalutya, ezifana ne-lipidomics, kunye nebhayoloji ye-molekyuli kunye neselula kuya kuphucula ukuqonda kwethu kweendawo kunye nexesha lexesha le-phospholipids kwiinkqubo zokubonisa. Ukuphonononga i-crosstalk phakathi kwe-lipid metabolism, ukuthengiswa kwe-membrane, kunye nokubonakaliswa kweselula kuya kutyhila iindlela zokulawula inoveli kunye neethagethi zonyango.
IiNdlela zeBhayoloji yeeNkqubo:
I-Leveraging systems biology approaches, kubandakanywa imodeli yemathematika kunye nohlalutyo lwenethiwekhi, iya kwenza ukuba kucaciswe impembelelo yehlabathi jikelele ye-phospholipids kwiinethiwekhi zesignali zeselula. Ukulinganisa intsebenziswano phakathi kwe-phospholipids, i-enzymes, kunye neziphumo zomqondiso ziya kucacisa iipropati ezivelayo kunye neendlela zempendulo ezilawula ukulawulwa kwendlela yomqondiso.
Iziphumo zonyango:
Ukuphanda ukunyanzeliswa kwe-phospholipids kwizifo, ezinjengomhlaza, ukuphazamiseka kwe-neurodeergenerative, kunye ne-syndromes ye-metabolic, inika ithuba lokuphuhlisa unyango olujoliswe kuyo. Ukuqonda iindima ze-phospholipids ekuqhubekeni kwesifo kunye nokuchonga izicwangciso ezintsha zokumodareyitha imisebenzi yabo kunesithembiso seendlela zonyango ezichanekileyo.
Ukuqukumbela, ulwazi oluhlala lukhula lwe-phospholipids kunye nokubandakanyeka kwabo okuyinkimbinkimbi kwisignali yeselula kunye nonxibelelwano lubonisa umda othakazelisayo wokuhlola okuqhubekayo kunye nefuthe elinokubakho lokuguqulela kwiinkalo ezahlukeneyo zophando lwe-biomedical.
IiReferensi:
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Di Paolo, G., & De Camilli, P. (2006). Phosphoinositides kulawulo lweeseli kunye ne-membrane dynamics. Indalo, 443(7112), 651-657.
Kooijman, EE, & Testerink, C. (2010). I-Phosphatidic acid: umdlali ophambili ovelayo ekubonakalisweni kweeseli. Iimpawu kwiSayensi yeZityalo, i-15 (6), i-213-220.
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Balla, T. (2013). Phosphoinositides: iilipids ezincinci ezinempembelelo enkulu kulawulo lweeseli. Uphononongo lwePhysiological, 93(3), 1019-1137.
Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2014). Ibhayoloji yeMolekyuli yeSeli (6th ed.). Inzululwazi yeGarland.
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Ixesha lokuposa: Dec-29-2023
