Le Fa'afefea o Phospholipids e Saofagā i le Cell Signaling ma Fesootaiga

I. Folasaga
Phospholipids o se vasega o lipids o vaega taua o sela sela. O lo latou fausaga tulaga ese, e aofia ai le ulu o le hydrophilic ma lua siʻusiʻu hydrophobic, e mafai ai e phospholipids ona fausia se fausaga bilayer, e avea o se pa puipui e vavae ese ai mea i totonu o le sela mai le siosiomaga i fafo. O lenei matafaioi faʻavae e taua mo le faʻamautuina o le faʻamaoni ma le faʻatinoga o sela i mea ola uma.
O faʻailoga ma fesoʻotaʻiga o mea taua ia e mafai ai e sela ona fegalegaleai le tasi ma le isi ma lo latou siosiomaga, e mafai ai ona tuʻufaʻatasia tali i faʻamalosi eseese. E mafai e sela ona faʻatonutonu le tuputupu aʻe, atinaʻe, ma le tele o galuega faʻaletino e ala i nei gaioiga. O auala faʻailoga e aofia ai le tuʻuina atu o faʻailoga, e pei o hormones poʻo neurotransmitters, lea e iloa e tali i luga o le sela sela, faʻaosoina se faʻalavelave faʻafuaseʻi e iʻu ai i se tali feaveaʻi.
O le malamalama i le matafaioi a le phospholipids i le faʻailoga ma fesoʻotaʻiga e taua tele mo le faʻamalamalamaina o lavelave o auala e fesoʻotaʻi ai sela ma faʻamaopoopo a latou gaioiga. O lenei malamalamaaga e i ai le tele o aʻafiaga i vaega eseese, e aofia ai le biology cell, pharmacology, ma le atinaʻeina o togafitiga faʻatatau mo le tele o faʻamaʻi ma faʻafitauli. E ala i le suʻesuʻeina o fesoʻotaʻiga lavelave i le va o le phospholipids ma le cell signaling, e mafai ai ona tatou maua ni faʻamatalaga i faiga faʻavae e pulea ai amioga ma galuega.

II. Fa'atulagaga o Phospholipids

A. Fa'amatalaga o le Fosfolipid Structure:
Phospholipids o molelaula amphipathic, o lona uiga o loʻo i ai i latou uma e lua hydrophilic (vai-toso) ma hydrophobic (vai-repelling) itulagi. O le fausaga autu o le phospholipid e aofia ai se mole glycerol o loʻo fusifusia i filifili gaʻo e lua ma se vaega ulu o loʻo i ai le phosphate. O si'usi'u hydrophobic, e aofia ai filifili ga'o ga'o, e fausia ai totonu o le lipid bilayer, ae fegalegaleai vaega ulu hydrophilic ma vai i luga uma o totonu ma fafo o le membrane. O lenei faatulagaga tulaga ese e mafai ai e phospholipids ona faʻapipiʻi i totonu o se lapisi, faʻatasi ai ma siʻusiʻu hydrophobic e faʻatatau i totonu ma ulu hydrophilic faʻasaga i siosiomaga vai i totonu ma fafo o le sela.

B. Matafaioi a Phopholipid Bilayer i Cell Membrane:
O le phospholipid bilayer o se vaega taua tele o le membrane cell, e maua ai se pa puipui semi-permeable e pulea le tafe o mea i totonu ma fafo o le sela. O lenei fa'aogaina fa'apitoa e mana'omia mo le fa'atumauina o le si'osi'omaga i totonu o le sela ma e taua tele mo fa'agasologa e pei o le fa'aogaina o mea'ai, fa'amama otaota, ma le puipuiga mai mea fa'aleagaina. I tua atu o lana matafaioi faʻavae, o le phospholipid bilayer e iai foi sona sao taua i le faʻailoga ma fesoʻotaʻiga.
O le faʻataʻitaʻiga mosaic vai o le membrane cell, na tuʻuina mai e Singer ma Nicolson i le 1972, o loʻo faʻamamafaina ai le malosi ma le heterogeneous natura o le membrane, faʻatasi ai ma phospholipids i taimi uma i le gaioiga ma polotini eseese faʻasalalau i le lipid bilayer. O lenei fausaga malosi e fa'avae i le fa'afaigofieina o fa'ailoga ma feso'ota'iga. Receptors, ion channels, ma isi faailoilo polotini o loʻo faʻapipiʻiina i totonu o le phospholipid bilayer ma e taua mo le iloa o faailo mai fafo ma tuʻuina atu i totonu o le sela.
E le gata i lea, o mea faʻaletino o phospholipids, e pei o lo latou suavai ma le gafatia e fausia ai lipid rafts, faʻamalosia le faʻatulagaina ma le faʻaogaina o palatini membrane e aʻafia i le faʻailoga cell. O le malosi o amioga a phospholipids e aʻafia ai le faʻaogaina ma le gaioiga o faʻamaoniga o polotini, ma faʻapea ona aʻafia ai le faʻapitoa ma le lelei o ala faʻailoga.
O le malamalama i le sootaga i le va o phospholipids ma le fausaga ma le gaioiga o le membrane cell e iai sona aafiaga loloto mo le tele o gaioiga olaola, e aofia ai le cellular homeostasis, atinaʻe, ma faʻamaʻi. O le tu'ufa'atasiga o le phospholipid biology ma su'esu'ega fa'ailoga o lo'o fa'aauau pea ona fa'ailoa mai fa'amatalaga taua i le lavelave o feso'ota'iga ma fa'amauina le folafolaga mo le atina'eina o togafiti fa'afoma'i fou.

III. Matafaioi a Phospholipids i Cell Signaling

A. Phospholipids pei o Molecules Fa'ailoga
Phospholipids, i le avea ai ma vaega iloga o sela sela, ua tulaʻi mai o ni molelaʻau faʻailoga taua i fesoʻotaʻiga sela. O vaega ulu hydrophilic o phospholipids, aemaise lava i latou o loʻo i ai inositol phosphates, e avea ma avefeau lona lua taua i ala faʻailoga eseese. Mo se faʻataʻitaʻiga, o le phosphatidylinositol 4,5-bisphosphate (PIP2) o loʻo galue o se mole faʻailoga e ala i le faʻapipiʻiina i totonu o le inositol trisphosphate (IP3) ma le diacylglycerol (DAG) i le tali atu i faʻalavelave faʻapitoa. O nei molelaula faʻailoga e maua mai i le lipid o loʻo i ai se sao taua i le faʻatonutonuina o le maualuga o le calcium intracellular ma le faʻagaoioia o le protein kinase C, ma faʻafefea ai le tele o gaioiga feaveaʻi e aofia ai le faʻalauteleina o le cell, eseesega, ma femalagaiga.
E le gata i lea, o phospholipids e pei o le phosphatidic acid (PA) ma le lysophospholipids ua lauiloa o ni mole faʻailoga e faʻaalia saʻo ai tali feaveaʻi e ala i fegalegaleaiga faʻatasi ma sini faʻapitoa o porotini. Mo se faʻataʻitaʻiga, o le PA o loʻo galue o se puluvaga autu i le tuputupu aʻe o le sela ma le faʻateleina e ala i le faʻagaoioia o polotini faʻailoga, ae o le lysophosphatidic acid (LPA) o loʻo aʻafia i le faʻatonutonuina o le cytoskeletal dynamics, cell survival, ma le femalagaiga. O nei matafaioi eseese a phospholipids e faʻamaonia ai lo latou taua i le faʻatulagaina o faʻailoga lavelave i totonu o sela.

B. A'afia o Phospholipids i Ala Fa'aliliuina Fa'ailoga
O le a'afia o phospholipids i ala fa'aliliuina fa'ailo ua fa'ata'ita'iina e la latou matafaioi taua i le fa'avasegaina o le gaioiga o tali fa'amaufa'atasi, ae maise G protein-coupled receptors (GPCRs). I luga o le ligand fusifusia i GPCRs, phospholipase C (PLC) ua faʻagaoioia, e taʻitaʻia ai le hydrolysis o le PIP2 ma le faʻatupuina o le IP3 ma le DAG. IP3 faʻaosoina le tuʻuina atu o le calcium mai faleoloa intracellular, aʻo faʻagaoioia e le DAG le protein kinase C, mulimuli ane faʻamutaina i le faʻatonutonuina o le faʻaaliga o le kenera, tuputupu aʻe o le cell, ma le faʻasalalauga synaptic.
E le gata i lea, o phosphoinositides, o se vasega o phospholipids, e fai ma nofoaga faʻapipiʻi mo faʻailoga polotini o loʻo aʻafia i auala eseese, e aofia ai ma faʻatonuina o fefaʻatauaʻiga o le membrane ma le actin cytoskeleton dynamics. O le fesoʻotaʻiga faʻamalosi i le va o phosphoinositides ma a latou polotini faʻafesoʻotaʻi e fesoasoani i le faʻaogaina o le vateatea ma le faʻaletino o mea e faʻaalia ai mea, ma faʻapipiʻiina ai tali feaveaʻi i faʻalavelave faʻapitoa.
O le tele o le aʻafia o phospholipids i le faʻailoga o le cell ma le faʻaliliuina o ala o loʻo faʻamamafaina ai lo latou taua o ni faʻatonuga autu o le homeostasis cellular ma galuega.

IV. Phospholipids ma Feso'ota'iga Intracellular

A. Phospholipids i le Intracellular Signaling
Phospholipids, o se vasega o lipids o loʻo i ai se vaega phosphate, e taʻalo taua i le faʻailogaina o le intracellular, faʻapipiʻiina le tele o gaioiga feaveaʻi e ala i lo latou auai i faʻailoga cascades. O se tasi o faʻataʻitaʻiga iloga o le phosphatidylinositol 4,5-bisphosphate (PIP2), o se phospholipid o loʻo i totonu o le membrane plasma. I le tali atu i faʻalavelave faʻapitoa, o le PIP2 ua vaeluaina i le inositol trisphosphate (IP3) ma le diacylglycerol (DAG) e le enzyme phospholipase C (PLC). O le IP3 e faʻaosoina ai le tuʻuina atu o le calcium mai faleoloa intracellular, aʻo faʻagaoioia e le DAG le protein kinase C, e iu ai ina faʻatonutonu galuega faʻaoga eseese e pei o le faʻalauteleina o le cell, faʻavasegaina, ma le toe faʻaleleia o le cytoskeletal.
E le gata i lea, o isi phospholipids, e aofia ai le phosphatidic acid (PA) ma le lysophospholipids, ua faʻamaonia e taua tele i le faʻailoga intracellular. PA fesoasoani i le faʻatonutonuina o le tuputupu aʻe o le sela ma le faʻateleina e ala i le galue o se faʻagaioia o polotini faʻailoga eseese. Lysophosphatidic acid (LPA) ua lauiloa ona o lona aʻafia i le faʻaogaina o le ola o le cell, migration, ma le cytoskeletal dynamics. O nei su'esu'ega o lo'o fa'amamafaina ai le 'ese'ese ma le taua o matafaioi a phospholipids e fai ma fa'ailoga molela'au i totonu o le sela.

B. Fegalegaleaiga o Phospholipids ma Porotini ma Receptors
E fegalegaleai foʻi Phospholipids ma polotini eseese ma tali e faʻafetaui ai ala faʻailoga telefoni. Aemaise lava, phosphoinositides, o se vaega laiti o phospholipids, e avea ma faʻavae mo le faʻafaigaluegaina ma le faʻagaoioia o faʻailoga faʻamaonia. Mo se faʻataʻitaʻiga, o le phosphatidylinositol 3,4,5-trisphosphate (PIP3) o loʻo galue o se faʻatonuga taua o le tuputupu aʻe o sela ma le faʻateleina e ala i le suʻeina o polotini o loʻo i ai le pleckstrin homology (PH) domains i le membrane plasma, ma amata ai faʻailoga faʻailoga. E le gata i lea, o le malosi o le fesoʻotaʻiga o phospholipids faʻatasi ai ma faʻailoga faʻapolopolo ma faʻafeiloaʻi e mafai ai ona faʻatautaia saʻo spatiotemporal o faʻailoga mea i totonu o le sela.

O fesoʻotaʻiga faʻapitoa o phospholipids ma polotini ma talipupuni e faʻamaonia ai la latou matafaioi taua i le faʻaogaina o auala faʻailoga intracellular, e iu ai ina saofagā i le faʻatonutonuina o galuega feaveaʻi.

V. Fa'atonuga o Phospholipids i le Fa'ailoga Cell

A. Enzymes ma Auala e A'afia ile Fofolipid Metabolism
Phospholipids o loʻo faʻatonutonuina malosi e ala i se fesoʻotaʻiga lavelave o enzymes ma auala, faʻaaafiaina lo latou tele ma galuega i le faʻailoga cell. O se tasi o ia auala e aofia ai le tuʻufaʻatasia ma le faʻaliliuina o le phosphatidylinositol (PI) ma ona faʻamaʻi phosphorylated, ua taʻua o le phosphoinositides. Phosphatidylinositol 4-kinases ma phosphatidylinositol 4-phosphate 5-kinases o enzymes ia e faʻamalosia le phosphorylation o le PI i tulaga D4 ma D5, faʻatupuina phosphatidylinositol 4-phosphate (PI4P) ma phosphatidylinositol 4,5-bisphosphate (PIP2), i le faasologa. I le isi itu, phosphatases, e pei o le phosphatase ma le tensin homolog (PTEN), dephosphorylate phosphoinositides, faʻatonutonuina o latou maualuga ma aʻafiaga i luga o le telefoni feaveaʻi.
E le gata i lea, o le de novo synthesis o phospholipids, aemaise phosphatidic acid (PA), e faʻasalalau e enzymes e pei o le phospholipase D ma le diacylglycerol kinase, ae o lo latou faʻaleagaina e faʻamalosia e phospholipases, e aofia ai le phospholipase A2 ma le phospholipase C. bioactive lipid mediators, e a'afia ai fa'agasologa o fa'ailoga sela ma saofagā i le tausiga o le homeostasis feavea'i.

B. Aafiaga ole Phopholipid Tulafono Fa'atonu ile Fa'agasologa ole Fa'ailoga
O le fa'atonutonuina o phospholipids e fa'aolaina ai a'afiaga i fa'agasologa o fa'ailoga sela e ala i le fa'avasegaina o gaioiga a molela'au fa'ailo taua ma ala. Mo se faʻataʻitaʻiga, o le faʻaaogaina o le PIP2 e le phospholipase C e maua ai le inositol trisphosphate (IP3) ma le diacylglycerol (DAG), e taʻitaʻia ai le tuʻuina atu o le calcium intracellular ma le faʻagaioiina o le protein kinase C, i le faasologa. O lenei faʻailoga faʻailoga e aʻafia ai tali feaveaʻi e pei o le neurotransmission, faʻamaʻi maso, ma le faʻaogaina o le cell immune.
E le gata i lea, o suiga i le maualuga o phosphoinositides e aʻafia ai le faʻafaigaluegaina ma le faʻagaoioia o polotini effector o loʻo i ai vaega o le lipid-binding, e aʻafia ai faiga e pei o le endocytosis, cytoskeletal dynamics, ma le femalagaiga o sela. E le gata i lea, o le faatonutonuina o le maualuga o le PA e phospholipases ma phosphatases e aʻafia ai le fefaʻatauaʻiga o membrane, tuputupu aʻe o sela, ma ala faʻailoga lipid.
O le fesoʻotaʻiga i le va o le phospholipid metabolism ma le cell signaling o loʻo faʻamamafaina ai le taua o le phospholipid tulafono faatonutonu i le faʻatumauina o le telefoni feaveaʻi ma le tali atu i mea faʻapitoa.

VI. Fa'ai'uga

A. Aotelega o Matafaioi Autu a Phospholipids i le Cell Signaling ma Fesootaiga

I se aotelega, o phospholipids latou te faia ni matafaioi taua i le faʻatulagaina o faʻailoga ma fesoʻotaʻiga i totonu ole tino olaola. O latou fausaga ma galuega eseese e mafai ai ona latou galulue o ni faʻatonuga faʻapitoa o tali telefoni feaveaʻi, faʻatasi ai ma matafaioi autu e aofia ai:

Fa'alapotopotoga Fa'aMembrane:

Phospholipids o loʻo fausia ai poloka faʻavae autu o paʻu feʻaveaʻi, faʻavaeina le fausaga faʻavae mo le tuʻufaʻatasia o vaega feaveaʻi ma le faʻaogaina o polotini faʻailoga. O lo latou gafatia e gaosia le lipid microdomains, e pei o le lipid rafts, e aʻafia ai le faʻalapotopotoga faʻapitoa o faʻailoga faʻalavelave ma a latou fegalegaleaiga, e aʻafia ai le faʻamaonia ma le lelei.

Fa'aliliuga Fa'ailoga:

Phospholipids galue o ni tagata faufautua autu i le faʻaliliuina o faʻailoga extracellular i tali intracellular. Phosphoinositides o loʻo avea ma mole faʻailoga, faʻavasegaina gaioiga o polotini effector eseese, aʻo gaʻo gaʻo saoloto ma lysophospholipids o loʻo galue o ni avefeʻau lona lua, e aʻafia ai le faʻagaoioia o faailoilo cascades ma faʻamatalaga gene.

Su'ega Fa'ailoga Fa'ailoga:

Phospholipids e saofagā i le faʻatonutonuina o ala faʻailoga eseese, faʻatinoina le pulea o gaioiga e pei o le faʻateleina o le cell, faʻavasegaina, apoptosis, ma tali puipuia. O lo latou aʻafia i le faʻatupuina o faʻasalalauga lipid bioactive, e aofia ai eicosanoids ma sphingolipids, faʻaalia atili ai lo latou aʻafiaga i fesoʻotaʻiga faʻamaʻi, metabolic, ma apoptotic signaling networks.
Feso'ota'iga Intercellular:

E auai foʻi Phospholipids i fesoʻotaʻiga faʻafesoʻotaʻi e ala i le faʻasaʻolotoina o le lipid mediators, e pei o prostaglandins ma leukotrienes, lea e faʻaogaina ai gaioiga a sela tuaoi ma asu, faʻatonutonuina le mumū, lagona o le tiga, ma le gaioiga vascular.
O le tele o sao o phospholipids i le faʻailoga ma fesoʻotaʻiga e faʻamaonia ai lo latou taua i le faatumauina o le homeostasis cellular ma le faʻamaopoopoina o tali o le physiological.

B. Fa'atonuga i le Lumana'i mo Su'esu'ega ile Phospholipids ile Cellular Signaling

A o faʻaauau pea ona faʻaalia le lavelave o matafaioi a le phospholipids i le cell signaling, o le tele o auala fiafia mo suʻesuʻega i le lumanaʻi ua faʻaalia, e aofia ai:

Fa'asalalauga fa'apitoa:

O le tu'ufa'atasia o metotia su'esu'e fa'apitoa, e pei o le lipidomics, fa'atasi ai ma le biology mole ma le cellular biology o le a fa'aleleia atili ai lo tatou malamalama i le fa'aogaina o le va'ai ma le fa'aletino o phospholipids i fa'agasologa o fa'ailoga. O le su'esu'eina o le felafolafoa'iga i le va o le metabolism o le lipid, fefa'ataua'iga o le membrane, ma le fa'ailoga feavea'i o le a fa'aalia ai faiga fa'atonutonu fou ma fa'amoemoega fa'afoma'i.

Va'aiga Fa'atonu Fa'atonu:

Ole fa'aogaina ole faiga ole biology approach, e aofia ai le fa'ata'ita'iga o le matematika ma au'ili'iliga feso'ota'iga, o le a mafai ai ona fa'amalamalamaina le a'afiaga ole lalolagi ole phospholipids ile feso'ota'iga fa'ailoga telefoni. O le fa'ata'ita'iina o feso'ota'iga i le va o phospholipids, enzymes, ma fa'ai'uga fa'ailo o le a fa'amalamalamaina ai mea fa'atupu fa'apea ma faiga fa'aalia e pulea ai le fa'atonutonuina o ala fa'ailoga.

Aafiaga fa'afoma'i:

O le suʻesuʻeina o le dysregulation o phospholipids i faʻamaʻi, e pei o le kanesa, neurodegenerative disorders, ma metabolic syndromes, e maua ai le avanoa e atiaʻe ai togafitiga faʻatatau. O le malamalama i matafaioi a le phospholipids i le alualu i luma o faʻamaʻi ma le faʻailoaina o taʻiala fou e faʻaleleia ai a latou gaioiga o loʻo i ai se folafolaga mo togafitiga faʻapitoa.

I le faaiuga, o le faʻalauteleina o le malamalama o phospholipids ma lo latou faʻalavelave faʻapitoa i faʻailoga telefoni feaveaʻi ma fesoʻotaʻiga e maua ai se tuaoi mataʻina mo le faʻaauau suʻesuʻega ma aʻafiaga faʻaliliuga i vaega eseese o suʻesuʻega biomedical.
Fa'asinomaga:
Balla, T. (2013). Phosphoinositides: lipine laiti ma le tele o aʻafiaga i le faʻatonutonuina o sela. Fisiological Reviews, 93(3), 1019-1137.
Di Paolo, G., & De Camilli, P. (2006). Phosphoinositides i le faatonutonuina o sela ma le malosi o le membrane. Natura, 443(7112), 651-657.
Kooijman, EE, & Testerink, C. (2010). Phosphatidic acid: ose tagata ta'alo autu i le fa'ailoga sela. Tulaga i La'au Saienisi, 15(6), 213-220.
Hilgemann, DW, & Ball, R. (1996). Faʻatonutonuina o le fatu Na(+), H(+)-fetufaʻi ma K(ATP) alavai pālolo e le PIP2. Saienisi, 273(5277), 956-959.
Kaksonen, M., & Roux, A. (2018). Mechanism of clathrin-mediated endocytosis. Natura Iloiloga Molecular Cell Biology, 19(5), 313-326.
Balla, T. (2013). Phosphoinositides: lipine laiti ma le tele o aʻafiaga i le faʻatonutonuina o sela. Fisiological Reviews, 93(3), 1019-1137.
Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2014). Molecular Biology of the Cell (6th ed.). Saienisi Garland.
Simons, K., & Vaz, WL (2004). Fa'ata'ita'iga faiga, lipid rafts, ma sela sela. Iloiloga Faaletausaga o Biophysics ma Biomolecular Structure, 33, 269-295.


Taimi meli: Tes-29-2023
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