I. Isingeniso
Ama-phospholipids ayisigaba sama-lipids ayizingxenye ezibalulekile zolwelwesi lwamaseli. Isakhiwo sabo esiyingqayizivele, esihlanganisa ikhanda le-hydrophilic kanye nemisila emibili ye-hydrophobic, ivumela ama-phospholipids ukuba enze isakhiwo se-bilayer, esisebenza njengesithiyo esihlukanisa okuqukethwe kwangaphakathi kweseli endaweni yangaphandle. Le ndima yesakhiwo ibalulekile ekugcineni ubuqotho nokusebenza kwamaseli kuzo zonke izinto eziphilayo.
Ukusayinda amaseli nokuxhumana kuyizinqubo ezibalulekile ezenza amangqamuzana akwazi ukusebenzisana namanye kanye nendawo yawo, okuvumela izimpendulo ezididiyelwe ezisusa ezihlukahlukene. Amaseli angalawula ukukhula, ukukhula, kanye nemisebenzi eminingi yomzimba ngalezi zinqubo. Izindlela zokubonisa amaseli zihilela ukudluliswa kwamasignali, njengamahomoni noma ama-neurotransmitters, atholwa ama-receptors kulwelwesi lweseli, okucupha uchungechunge lwezenzakalo eziholela ekugcineni ekuphenduleni kweselula okuthile.
Ukuqonda indima ye-phospholipids ekuboniseni amangqamuzana nokuxhumana kubalulekile ekwembuleni ubunzima bendlela amaseli axhumana ngayo futhi axhumanise imisebenzi yawo. Lokhu kuqonda kunemiphumela efinyelela kude emikhakheni eyahlukene, okuhlanganisa i-cell biology, i-pharmacology, kanye nokuthuthukiswa kwezindlela zokwelapha ezihlosiwe zezifo eziningi neziyaluyalu. Ngokuhlolisisa ukuxhumana okuyinkimbinkimbi phakathi kwama-phospholipids nokusayina kwamaseli, singathola imininingwane ngezinqubo ezibalulekile ezilawula ukuziphatha nokusebenza kwamaselula.
II. Isakhiwo se-Phospholipids
A. Incazelo Yesakhiwo Se-Phospholipid:
Ama-phospholipids ama-amphipathic molecules, okusho ukuthi anazo zombili izifunda ze-hydrophilic (eziheha amanzi) kanye ne-hydrophobic (exosha amanzi). Isakhiwo esiyisisekelo se-phospholipid siqukethe i-molecule ye-glycerol eboshwe emaketangeni amabili e-fatty acid kanye neqembu lekhanda eliqukethe i-phosphate. Imisila ye-hydrophobic, eyakhiwe ngamaketanga e-fatty acid, yakha ingaphakathi le-lipid bilayer, kuyilapho amaqembu ekhanda e-hydrophilic ehlangana namanzi kokubili kwendawo yangaphakathi nangaphandle ye-membrane. Lolu hlelo oluyingqayizivele luvumela ama-phospholipids ukuthi azihlanganisele ku-bilayer, enemisila ye-hydrophobic eqondiswe ngaphakathi kanye namakhanda e-hydrophilic abheke endaweni enamanzi ngaphakathi nangaphandle kweseli.
B. Iqhaza Le-Phospholipid Bilayer Ku-Cell Membrane:
I-phospholipid bilayer iyingxenye yesakhiwo esibalulekile yolwelwesi lwamaseli, ehlinzeka ngomgoqo ovumeleke kancane olawula ukugeleza kwezinto ukungena nokuphuma kuseli. Lokhu kungenela okukhethiwe kubalulekile ekugcineni indawo yangaphakathi yengqamuzana futhi kubalulekile ezinqubweni ezinjengokuthatha izakhi, ukuqedwa kukadoti, nokuvikelwa kuma-ejenti ayingozi. Ngaphandle kwendima yayo yesakhiwo, i-phospholipid bilayer nayo idlala indima ebalulekile ekuboniseni amaseli nokuxhumana.
Imodeli ye-mosaic ewuketshezi yolwelwesi lwamaseli, eyahlongozwa nguSinger noNicolson ngo-1972, igcizelela imvelo eguquguqukayo nehlukahlukene yolwelwesi, olunama-phospholipids ahlala enyakaza kanye namaprotheni ahlukahlukene ahlakazeke kuyo yonke i-lipid bilayer. Lesi sakhiwo esiguquguqukayo siyisisekelo ekusizeni ukusayina kwamaseli nokuxhumana. Izamukeli, iziteshi ze-ion, namanye amaprotheni amasignali ashumekwe ngaphakathi kwe-phospholipid bilayer futhi abalulekile ekuboneni amasignali angaphandle futhi awadlulisele ngaphakathi kweseli.
Ngaphezu kwalokho, izici ezingokomzimba zama-phospholipids, njengokugcwala kwawo kanye nekhono lokwakha ama-lipid rafts, zithonya ukuhlelwa nokusebenza kwamaprotheni olwelwesi oluthintekayo ekuboniseni amaseli. Ukuziphatha okuguquguqukayo kwama-phospholipids kuthinta ukwenziwa kwasendaweni nomsebenzi wamaphrotheni amasignali, ngaleyo ndlela kube nomthelela ekucaceni nasekusebenzeni kahle kwezindlela zokusayina.
Ukuqonda ubudlelwano phakathi kwama-phospholipids kanye nesakhiwo kanye nomsebenzi wolwelwesi lweseli kunemithelela ejulile ezinqubweni eziningi zebhayoloji, okuhlanganisa i-homeostasis yeselula, ukuthuthukiswa, nesifo. Ukuhlanganiswa kwebhayoloji ye-phospholipid nocwaningo lokusayina amaseli kuyaqhubeka nokwembula imininingwane ebucayi eyinkimbinkimbi yokuxhumana kwamaseli futhi kunesithembiso sokuthuthukiswa kwamasu okwelapha amasha.
III. Iqhaza le-Phospholipids Ekuboniseni Iseli
A. Ama-Phospholipids Njengama-Signaling molecule
Ama-phospholipids, njengezakhi ezivelele zolwelwesi lwamangqamuzana, avele njengama-molecule abalulekile okubonisa ekuxhumaneni kwamaseli. Amaqembu ekhanda e-hydrophilic e-phospholipids, ikakhulukazi lawo aqukethe i-inositol phosphates, asebenza njengezithunywa zesibili ezibalulekile emigwaqweni ehlukahlukene yokusayina. Isibonelo, i-phosphatidylinositol 4,5-bisphosphate (PIP2) isebenza njenge-molecule ebonisayo ngokuklebhulwa ku-inositol trisphosphate (IP3) kanye ne-diacylglycerol (DAG) ngokusabela ku-extracellular stimuli. Lawa mamolekyuli okusayina asuselwa ku-lipid adlala indima ebalulekile ekulawuleni amazinga e-calcium ye-intracellular kanye nokwenza kusebenze i-protein kinase C, ngaleyo ndlela alungise izinqubo ezihlukahlukene zamaselula ezihlanganisa ukwanda kwamangqamuzana, ukuhlukaniswa, nokufuduka.
Ngaphezu kwalokho, ama-phospholipids afana ne-phosphatidic acid (PA) kanye ne-lysophospholipids aye aqashelwa njengama-molecule abonisayo athonya ngokuqondile izimpendulo zamaselula ngokusebenzisana nemigomo ethile yamaprotheni. Isibonelo, i-PA isebenza njengomlamuleli oyinhloko ekukhuleni kwamangqamuzana nokwanda ngokuvula amaprotheni okubonisa, kuyilapho i-lysophosphatidic acid (LPA) ihilelekile ekulawuleni amandla e-cytoskeletal, ukusinda kwamaseli, nokufuduka. Lezi zindima ezihlukahlukene ze-phospholipids zigqamisa ukubaluleka kwazo ekuhleleni ama-cascade okusayina okuyinkimbinkimbi ngaphakathi kwamaseli.
B. Ukubandakanywa kwe-Phospholipids Ezindleleni Zokushintshwa Kwesiginali
Ukubandakanyeka kwama-phospholipids emigwaqweni yokudlulisela isignali kubonakala ngendima yawo ebalulekile ekuhleleni umsebenzi wama-receptor aboshwe ulwelwesi, ikakhulukazi ama-G protein-coupled receptors (GPCRs). Lapho i-ligand ibophezela kuma-GPCRs, i-phospholipase C (PLC) iyasebenza, okuholela ku-hydrolysis ye-PIP2 kanye nokukhiqizwa kwe-IP3 ne-DAG. I-IP3 iqala ukukhishwa kwe-calcium ezitolo ze-intracellular, kuyilapho i-DAG yenza i-protein kinase C isebenze, ekugcineni ifinyelele ekulawuleni isisho sofuzo, ukukhula kwamaseli, kanye nokudluliselwa kwe-synaptic.
Ngaphezu kwalokho, i-phosphoinositides, ikilasi lama-phospholipids, isebenza njengendawo yokumisa ama-protein abandakanyeka ezindleleni ezihlukahlukene, okuhlanganisa lawo alawula ukushushumbiswa kwe-membrane kanye ne-actin cytoskeleton dynamics. Ukusebenzisana okuguquguqukayo phakathi kwe-phosphoinositides kanye namaprotheni awo asebenzisanayo kunomthelela ekulawuleni indawo kanye nesikhashana yezenzakalo zokubonisa, ngaleyo ndlela kubumba izimpendulo zamaselula ekuvuseleleni okungaphandle kwe-extracellular.
Ukubandakanyeka okuhlukahlukene kwe-phospholipids ekuboniseni amaseli kanye nezindlela zokudlulisela isignali kugcizelela ukubaluleka kwazo njengabalawuli ababalulekile be-homeostasis yamaselula kanye nomsebenzi.
IV. Phospholipids kanye ne-Intracellular Communications
A. Phospholipids ku-Intracellular Signaling
Ama-phospholipids, ikilasi lama-lipids aqukethe iqembu le-phosphate, adlala indima ebalulekile ekusayineni kwe-intracellular, ahlele izinqubo ezihlukahlukene zamaselula ngokubandakanyeka kwawo ekuboniseni ama-cascade. Isibonelo esisodwa esivelele i-phosphatidylinositol 4,5-bisphosphate (PIP2), i-phospholipid etholakala kulwelwesi lwe-plasma. Ukusabela ekushukumiseni okungaphandle kwamaseli, i-PIP2 igaywa ibe yi-inositol trisphosphate (IP3) kanye ne-diacylglycerol (DAG) nge-enzyme phospholipase C (PLC). I-IP3 iqala ukukhishwa kwe-calcium ezitolo ze-intracellular, kuyilapho i-DAG yenza i-protein kinase C isebenze, ekugcineni ilawule imisebenzi yamaselula ehlukahlukene njengokwanda kwamaseli, ukuhlukaniswa, nokuhlelwa kabusha kwe-cytoskeletal.
Ukwengeza, amanye ama-phospholipids, okuhlanganisa i-phosphatidic acid (PA) kanye ne-lysophospholipids, ahlonzwe njengabalulekile ekusayineni kwe-intracellular. I-PA ibamba iqhaza ekulawuleni ukukhula kwamangqamuzana nokwanda ngokusebenza njenge-activator yamaprotheni ahlukahlukene okubonisa. I-Lysophosphatidic acid (LPA) yaziwa ngokubamba iqhaza kwayo ekuguquleni ukusinda kwamaseli, ukufuduka, kanye namandla e-cytoskeletal. Lokhu okutholakele kugcizelela izindima ezihlukahlukene nezibalulekile ze-phospholipids njengama-molecule abonisa ngaphakathi kweseli.
B. Ukusebenzisana Kwe-Phospholipids Namaprotheni Nezamukeli
I-Phospholipids iphinde ihlanganyele namaprotheni ahlukahlukene kanye nama-receptors ukulungisa izindlela zokubonisa amaselula. Ngokuphawulekayo, i-phosphoinositides, i-subgroup of phospholipids, isebenza njengezinkundla zokuqashwa nokusebenza kwamaprotheni okusayina. Isibonelo, i-phosphatidylinositol 3,4,5-trisphosphate (PIP3) isebenza njengesilawuli esibalulekile sokukhula kwamangqamuzana nokwanda ngokuqasha amaprotheni aqukethe izizinda ze-pleckstrin homology (PH) kulwelwesi lwe-plasma, ngaleyo ndlela kuqalwe izehlakalo zokusayina ezansi nomfula. Ngaphezu kwalokho, ukuhlangana okuguquguqukayo kwe-phospholipids namaprotheni okusayina kanye nama-receptors kuvumela ukulawulwa kwe-spatiotemporal okunembile kwemicimbi yokusayina ngaphakathi kweseli.
Ukusebenzisana okuxubile kwama-phospholipids namaprotheni nama-receptors kugqamisa indima yawo ebalulekile ekuhlelweni kwezindlela zokusayina ze-intracellular, ekugcineni kube nomthelela ekulawuleni imisebenzi yamaselula.
V. Ukulawulwa Kwe-Phospholipids Ekuboniseni Iseli
A. Ama-Enzyme kanye Nezindlela Ezibandakanyeka Ku-Phospholipid Metabolism
Ama-phospholipids alawulwa ngokuguquguqukayo ngenethiwekhi eyinkimbinkimbi yama-enzyme nezindlela, ezithonya ukuchichima kwawo nokusebenza ekuboniseni amaseli. Enye indlela enjalo ibandakanya ukuhlanganiswa kanye nokushintshwa kwe-phosphatidylinositol (PI) kanye nokuphuma kwayo kwe-phosphorylated, eyaziwa ngokuthi i-phosphoinositides. I-Phosphatidylinositol 4-kinases kanye ne-phosphatidylinositol 4-phosphate 5-kinases ama-enzyme enza i-phosphorylation ye-PI endaweni ye-D4 ne-D5, ekhiqiza i-phosphatidylinositol 4-phosphate (PI4P) kanye ne-phosphatidys-4, i-IPlyitol-phosphate (Plysitol-phosphate) , i-IPlysitol 2. Ngakolunye uhlangothi, ama-phosphatase, afana ne-phosphatase ne-tensin homolog (PTEN), i-dephosphorylate phosphoinositides, elawula amazinga awo kanye nomthelela ekusayineni kwamaselula.
Ngaphezu kwalokho, i-de novo synthesis ye-phospholipids, ikakhulukazi i-phosphatidic acid (PA), iqondiswa ama-enzyme afana ne-phospholipase D ne-diacylglycerol kinase, kuyilapho ukuwohloka kwawo kubangelwa ama-phospholipases, okuhlanganisa i-phospholipase A2 ne-phospholipase C. Lawa mazinga e-enzymatic alawula ngokuhlanganyela i-theory. i-bioactive lipid mediators, enomthelela ezinqubweni ezihlukahlukene zokubonisa amaseli futhi ibe negalelo ekugcinweni kwe-homeostasis yamaselula.
B. Umthelela Wokulawulwa Kwe-Phospholipid Ezinqubweni Zokusayina Amaseli
Ukulawulwa kwama-phospholipids kunemiphumela ejulile ezinqubweni zokubonisa amaseli ngokumodela imisebenzi yama-molecule abalulekile wokusayina nezindlela. Isibonelo, inzuzo ye-PIP2 nge-phospholipase C ikhiqiza i-inositol trisphosphate (IP3) ne-diacylglycerol (DAG), okuholela ekukhululweni kwe-intracellular calcium nokusebenza kweprotein kinase C, ngokulandelana. Lokhu kugijinywa kwezimpawu kunomthelela ekuphenduleni kwamaselula okufana ne-neurotransmission, ukufinyela kwemisipha, nokusebenza kwamaseli omzimba.
Ngaphezu kwalokho, izinguquko emazingeni e-phosphoinositides zithinta ukuqashwa nokusebenza kwamaprotheni asebenzayo aqukethe izizinda ezibopha i-lipid, ezithinta izinqubo ezifana ne-endocytosis, i-cytoskeletal dynamics, kanye nokufuduka kwamaseli. Ukwengeza, ukulawulwa kwamazinga e-PA ngama-phospholipases nama-phosphatase kuthonya ukushushumbiswa kwe-membrane, ukukhula kwamaseli, nezindlela zokubonisa i-lipid.
Ukuxhumana phakathi kwe-phospholipid metabolism kanye nokusayina kwamaseli kugcizelela ukubaluleka kokulawulwa kwe-phospholipid ekugcineni ukusebenza kwamaselula nokusabela ekushukumiseni okungaphandle kwamaseli.
VI. Isiphetho
A. Isifinyezo Sezindima Eziyinhloko Ze-Phospholipids Ekuboniseni Amaseli Nokuxhumana
Kafushane, ama-phospholipids adlala indima ebalulekile ekuhleleni ukusayinda kwamaseli kanye nezinqubo zokuxhumana ngaphakathi kwezinhlelo zebhayoloji. Ukuhlukahluka kwabo kwesakhiwo nokusebenza kubenza bakwazi ukusebenza njengabalawuli abaguquguqukayo bezimpendulo zamaselula, ngezindima ezibalulekile ezihlanganisa:
Inhlangano ye-Membrane:
Ama-phospholipids akha izakhi zokwakha eziyisisekelo zolwelwesi lwamangqamuzana, esungula uhlaka lwesakhiwo sokuhlukaniswa kwezingxenye zamangqamuzana kanye nokwenza kwasendaweni kwamaprotheni amasignali. Amandla abo okukhiqiza ama-microdomain e-lipid, njengama-lipid rafts, athonya inhlangano yendawo yezindawo zokusayina nokusebenzisana kwazo, kube nomthelela wokucaciswa kokusayina nokusebenza kahle.
Ukuguqulwa Kwesiginali:
Ama-phospholipids asebenza njengabalamuli ababalulekile ekudluliseleni amasiginali angaphandle kweseli ezimpendulweni ze-intracellular. Ama-Phosphoinositides asebenza njengama-molecule abonisa izimpawu, ashintsha imisebenzi yamaprotheni anemiphumela ehlukahlukene, kuyilapho ama-fatty acids amahhala kanye nama-lysophospholipids esebenza njengezithunywa zesibili, ezithonya ukwenziwa kusebenze kokubonisa ama-cascade kanye ne-gene expression.
Ukuguquguquka Kokusayina Kweseli:
Ama-phospholipids afaka isandla ekulawulweni kwezindlela zokusayina ezahlukahlukene, alawula izinqubo ezinjengokwanda kwamaseli, ukuhlukaniswa, i-apoptosis, kanye nezimpendulo zokuzivikela komzimba. Ukuzibandakanya kwabo ekukhiqizeni abaxhumanisi be-lipid be-bioactive, okuhlanganisa i-eicosanoids nama-sphingolipids, kukhombisa ngokuqhubekayo umthelela wabo kumanethiwekhi okubonisa ukuvuvukala, umzimba, kanye ne-apoptotic.
Ukuxhumana Kwamaselula:
I-Phospholipids iphinde ibambe iqhaza ekukhulumisaneni kwe-intercellular ngokukhululwa kwabaxhumanisi be-lipid, njenge-prostaglandin ne-leukotrienes, ehlela imisebenzi yamangqamuzana angomakhelwane nezicubu, ukulawula ukuvuvukala, ukubona ubuhlungu, nokusebenza kwe-vascular.
Iminikelo ehlukahlukene ye-phospholipids ekuboniseni amaseli kanye nokuxhumana igcizelela ukubaluleka kwayo ekugcineni i-homeostasis yeselula kanye nokuxhumanisa izimpendulo zomzimba.
B. Izikhombisi-ndlela Zesikhathi esizayo Zokucwaninga Nge-Phospholipids Ekuboniseni Amaselula
Njengoba izindima eziyinkimbinkimbi ze-phospholipids ekusayineni kwamaseli ziqhubeka nokwembulwa, izindlela ezimbalwa ezijabulisayo zocwaningo oluzayo ziyavela, okuhlanganisa:
Izindlela ze-Interdisciplinary:
Ukuhlanganiswa kwamasu athuthukisiwe okuhlaziya, afana ne-lipidomics, ne-molecular and cellular biology kuzothuthukisa ukuqonda kwethu ukuguquguquka kwendawo kanye nesikhashana kwe-phospholipids ezinqubweni zokusayina. Ukuhlola i-crosstalk phakathi kwe-lipid metabolism, ukushushumbiswa kwe-membrane, nokusayina kwamaselula kuzoveza izindlela ezintsha zokulawula kanye nezinhloso zokwelapha.
Imibono Yebhayoloji Yesistimu:
Izindlela zebhayoloji yokusizakala, okuhlanganisa ukumodela kwezibalo kanye nokuhlaziywa kwenethiwekhi, kuzovumela ukucaciswa komthelela womhlaba wonke wama-phospholipids kumanethiwekhi okubonisa amaselula. Ukumodela ukusebenzisana phakathi kwama-phospholipids, ama-enzyme, kanye nemiphumela yokusayina kuzocacisa izakhiwo ezivelayo kanye nezindlela zempendulo ezilawula ukulawulwa kwendlela yokusayina.
Imithelela yokwelapha:
Ukuphenya ukungasebenzi kahle kwe-phospholipids ezifweni, ezinjengomdlavuza, ukuphazamiseka kwe-neurodeergenerative, kanye ne-metabolic syndromes, kunikeza ithuba lokuthuthukisa izindlela zokwelapha ezihlosiwe. Ukuqonda izindima zama-phospholipids ekuqhubekeleni phambili kwesifo kanye nokuhlonza amasu amasha okushintsha imisebenzi yawo kunesithembiso sezindlela zokwelashwa ezinembayo.
Sengiphetha, ulwazi olukhula njalo lwama-phospholipid kanye nokubandakanyeka kwawo okuyinkimbinkimbi ekuboniseni amaselula nokuxhumana kuveza umngcele othakazelisayo wokuhlola okuqhubekayo kanye nomthelela wokuhumusha ongaba khona emikhakheni ehlukahlukene yocwaningo lwe-biomedical.
Izithenjwa:
U-Balla, T. (2013). I-Phosphoinositides: ama-lipids amancane anomthelela omkhulu ekulawuleni amaseli. Ukubuyekezwa Komzimba, 93(3), 1019-1137.
U-Di Paolo, G., & De Camilli, P. (2006). I-Phosphoinositides ku-cell regulation kanye ne-membrane dynamics. Imvelo, 443(7112), 651-657.
Kooijman, EE, & Testerink, C. (2010). I-Phosphatidic acid: umdlali oyinhloko ovelayo ekusayineni kweseli. Amathrendi kuSayensi Yezitshalo, 15(6), 213-220.
U-Hilgemann, DW, & Ball, R. (1996). Ukulawulwa kwe-cardiac Na(+), H(+)-exchange kanye neziteshi ze-potassium ze-K(ATP) nge-PIP2. Isayensi, 273(5277), 956-959.
Kaksonen, M., & Roux, A. (2018). Izindlela ze-endocytosis ye-clathrin-mediated. Ukubuyekezwa Kwemvelo I-Molecular Cell Biology, 19(5), 313-326.
U-Balla, T. (2013). I-Phosphoinositides: ama-lipids amancane anomthelela omkhulu ekulawuleni amaseli. Ukubuyekezwa Komzimba, 93(3), 1019-1137.
Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2014). I-Molecular Biology yeseli (6th ed.). Isayensi yeGarland.
Simons, K., & Vaz, WL (2004). Amamodeli wezinhlelo, ama-lipid raft, nama-membrane weseli. Ukubuyekezwa Konyaka kwe-Biophysics kanye ne-Biomolecular Structure, 33, 269-295.
Isikhathi sokuthumela: Dec-29-2023
