Ho bohlokoa haholo ho utloisisa hore na motsoako oa k'holeseterole ho sebete o hlaha joang. Haeba u hlahloba taba ena ka botlalo, kapele-pele ho tla totobala hore na sebete se amana joang le karolo ena ea lintho tse phelang. Empa pele, u lokela ho hopola hore ntho eo le eona e na le lebitso, leo hape le sebelisoang khafetsa, e leng k'holeseterole.
Joalokaha ho se ho boletsoe ka holimo, ntho ena ke motsoako oa lintho tse phelang 'me e fumanoa linthong tsohle tse phelang. Ke karolo ea bohlokoa ea lipids.
Khatiso e phahameng ka ho fetisisa e bonoa lihlahisoa tsa tlhaho ea liphoofolo. Empa ka lihlahisoa tsa limela ho na le karolo e nyane feela ea komporo ena.
Ho bohlokoa hape ho hlokomela 'nete ea hore, hammoho le lijo ke karolo ea 20 lekholong feela ea kakaretso ea k'holeseterole e kenang, karolo ea 80 lekholong ea' mele e hlahisa ka boithatelo. Ka tsela, ea ntho eohle e kopantsoeng a le mong, 50% e thehoa ka ho toba ka har'a sebete. Sena se etsahala boemong ba sele, 30% e setseng e hlahisoa ka mala le letlalo.
'Mele oa motho o na le mefuta e mengata ea motsoako ona. Ka nako e ts'oanang, ho lokela ho hopoloa hore ke sistimi ea hematopoietic e tletse ntho ena. Cholesterol maling ke karolo ea metsoako e rarahaneng e nang le protheine, mefuta e joalo e bitsoa lipoprotein.
Liphetoho li ka ba tsa mefuta e 'meli:
- HDL - ba le letsoalo le phahameng haholo, ba bitsoa ba batle;
- LDL - ba le letsoalo le tlase, lintho tsena li bitsoa tse mpe.
Ke mofuta oa bobeli o isang batho kotsing. Kamora hore li fokotsehe, tse nang le likristale tsa ntho, li qala ho bokellana ka mokhoa oa li-plaque maboteng a methapo ea mali ea tsamaiso ea potoloho, e nang le boikarabello ba ho tsamaisa mali. Ka lebaka leo, ts'ebetso ena e fetoha sesosa sa nts'etsopele 'meleng oa pathology e joalo ka atherosclerosis.
Tsoelo-pele ea atherosclerosis e lebisa ho nts'etsopele ea maloetse a mangata a tebileng.
Likarolo tsa motheo tsa khokahano
Joalokaha ho boletsoe kaholimo, ntho ena e ka ba molemo ho batho, ehlile, feela ha re bua ka HDL.
Motheong oa sena, ho hlakile hore polelo ea hore cholesterol e kotsi ho batho ke phoso.
Cholesterol ke karolo e sebetsang ea bioloji:
- e nka karolo tlhahisong ea lihormone tsa thobalano;
- e tiisa ts'ebetso e tloaelehileng ea li-receptor tsa serotonin bokong;
- karolo ea mantlha ea bile, hammoho le vithamine D, e ikarabellang bakeng sa ho monya mafura;
- e thibela ts'ebetso ea ts'enyeho ea likarolo tsa intracellular tlasa ts'usumetso ea li-radicals tsa mahala.
Empa hammoho le thepa e ntle, ntho ena e ka ba le kotsi ho bophelo ba motho. Mohlala, LDL e ka baka nts'etsopele ea maloetse a tebileng, haholo kenya letsoho kholisong ea atherosclerosis.
Sebeteng, biocomponent e hlophisitsoe ka tlas'a tšusumetso ea HMG redutase. Ena ke eona enzyme ea mantlha e amehang ho biosynthesis. Ho thibela tlhaho ho etsahala tlasa ts'usumetso ea maikutlo a fosahetseng.
Ts'ebetso ea motsoako oa ntho e teng ka har'a sebete e na le kamano e fapaneng le tekanyetso ea motsoako o kenang 'meleng oa motho ka lijo.
Le e bobebe, ts'ebetso ena e hlalosoa ka tsela ena. Sebete se ikemela se laola maemo a k'holeseterole. Ha motho a qeta ho ja lijo tse nang le motsoako ona, ntho e fokolang e hlahisoa liseleng tsa setho, 'me haeba re ela hloko hore mafura a jeoa hammoho le lihlahisoa tse nang le ona, ebe mohato ona oa taolo o bohlokoa haholo.
Likarolo tsa motsoako oa taba
Batho ba baholo ba phetseng hantle ba hlophisa HDL ka tekanyo e ka bang 1 g / ka letsatsi mme ba nka 0,3 g / ka letsatsi.
Karolo e sa fetoheng ea k'holeseterole maling e na le boleng bo joalo - 150-200 mg / dl. E bolokiloe haholo-holo ka ho laola boemo ba motsoako oa denovo.
Ho bohlokoa ho hlokomela hore motsoako oa HDL le LDL oa tlhaho ea tlhaho o laoloa ka mokhoa o itseng ke lijo.
Cholesterol, ka bobeli ho tsoa ho lijo ebile e entsoe ka har'a sebete, e sebelisoa ha ho etsoa litho, ka har'a motsoako oa lihormone tsa steroid le li-acid acid. Karolo e kholo ka ho fetisisa ea ntho ena e sebelisoa ho motsoako oa li-acids tsa bile.
Ho kenella ha HDL le LDL ka lisele ho bolokoa maemong a tsitsitseng ke mekhoa e meraro e fapaneng:
- Taolo ea Ts'ebetso ea HMGR
- Taolo ea cholesterol ea mahala e kenelletseng ka ts'ebetso ea sterol ea O-acyltransferase, SOAT1 le SOAT2 e nang le SOAT2, e leng eona karolo e ka sehloohong e sebetsang seaparong. Khetho ea pele ea li-enzyme tsena e ne e le ACAT bakeng sa acyl-CoA: acyltransferase cholesterol. Li-Enzymes ACAT, ACAT1, le ACAT2 ke acetyl CoA acetyltransferase 1 le 2.
- Ka ho laola maemo a k'holeseterole ea plasma ka ho tsamaisa li-receptor tsa LDL-Mediated receptor le lipalangoang tse fapaneng tsa HDL.
Taolo ea ts'ebetso ea HMGR ke mokhoa oa mantlha oa ho laola boemo ba biosynthesis ea LDL le HDL.
Enzyme e laoloa ke mekhoa e mene e fapaneng:
- Thibelo ea maikutlo
- taolo ea polelo ea tlhaho;
- tekanyo ea ho senya ea enzyme;
- phosphorylation-dephosphorylation
Mehato ea pele e meraro ea taolo e sebetsa ka kotloloho ho ntho ka boeona. Cholesterol e sebetsa e le sebapali sa ho fana ka maikutlo ka HMGR e seng e ntse e le teng ebile e baka tšilafalo ea enzyme kapele. Qetellong ke litholoana tsa polyubiquitilation ea HMGR le ho senyeha ha eona ho protheine. Bokhoni bona ke phello ea sebaka se matla sa HMGR SSD.
Ntle le moo, ha k'holeseterole e le ngata, palo ea mRNA bakeng sa HMGR e fokotseha ka lebaka la polelo ea gene e fokotsehileng.
Lirosa tse amehang moetlong
Haeba karolo ea kantle ho naha e laoloa ka phetoho e kopanetsoeng, ts'ebetso ena e tla etsoa ka lebaka la phosphorylation le dephosphorylation.
Enzyme e sebetsa haholo ka sebopeho se sa ngolisoang. Phosphorylation ea enzyme e fokotsa tšebetso ea eona.
HMGR e phosphorylated ke kinase e hlahisang li-protein tsa AMP, AMPK. AMPK ka boeona e sebetsa ke phosphorylation.
Phosphorylation ea AMPK e tšoaelitsoe ke bonyane li-enzyme tse peli, e leng:
- Kinase ea mantlha e ikarabellang bakeng sa ts'ebetso ea AMPK ke LKB1 (sebete kinase B1). LKB1 e qalile e tsejoa e le mofuta oa liphatsa tsa lefutso ho batho ba nang le phetoho ea methapo ea kutlo e ikhethileng ho lefu la Putz-Jegers, PJS. LKB1 e fumaneha hape e fetoha phetoho ho pulmonary adenocarcinoma.
- Phosphorylating ea enzyme ea bobeli ea phosphorylating ke protheine ea kinase kinase kinase (CaMKKβ) ea "phodphorylating". CaMKKβ e kenya phosphorylation ea AMPK ho arabela keketseho ea intracellular Ca2 + ka lebaka la mokoloto oa mesifa.
Taolo ea HMGR ka liphetoho tse kopanetsoeng e lumella HDL ho hlahisoa. HMGR e sebetsa haholo seterekeng sa dephosphorylated. Phosphorylation (Ser872) e ts'oaroa ke enzyme ea AMP-activated protein kinase (AMPK), ketsahalo eo hape e laoloang ke phosphorylation.
Phosphorylation ea AMPK e ka hlaha ka lebaka la bonyane li-enzyme tse peli:
- LKB1;
- CaMKKβ.
Dephosphorylation ea HMGR, e e khutlisetsang maemong a sebetsang haholoanyane, e etsoa ka ts'ebetso ea liprotheine tsa protheine tsa lelapa la 2A. Tatellano ena eu lumella ho laola tlhahiso ea HDL.
Ke eng e amang mofuta oa cholesterol?
PP2A ea ts'ebetso e fumaneha ka li-isoforms tse peli tse fapaneng tse kentsoeng ke liphatsa tse peli tse khethiloeng e le PPP2CA le PPP2CB. Li-isoforms tse peli tse ka sehloohong tsa PP2A ke enzyme ea mantlha ea heterodimeric le heterotrimeric holoenzyme.
Enzyme ea mantlha ea PP2A e entsoe ka "scaffold substrate" (eo pele e neng e bitsoa A subunit) le catuniti subunit (C subunit). Subunit ea "catalyatic" e thathamisitsoe ke mofuta oa PPP2CA, 'me "catunthi" e kentsoe mofuta oa PPP2CB.
Sebopeho sa aff scaffold se kenyelelitsoe ke mofuta oa PPP2R1A le β subunit ke mofuta oa PPP2R1B. Enzyme ea mantlha, PP2A e sebelisana le subunit e laoloang ea melao hore e bokane ka holoenzyme.
Li-subunits tsa taolo ea PP2A li kenyelletsa malapa a mane (a neng a bitsoa B-subunits), ao e 'ngoe le e' ngoe e nang le li-isoform tse 'maloa tse kentsoeng ke mefuta e fapaneng.
Ha joale, ho na le mefuta e 15 e fapaneng ea "subPitit" ea PP2A ea mantlha ea mantlha.
PPP2R ke e 'ngoe ea li-subunits tsa 15 tse fapaneng tsa taolo ea PP2A. Lihormone tse kang glucagon le adrenaline hampe li ama cholesterol biosynthesis ka ho eketsa tšebetso ea litlatsetso tse ikhethileng tsa lelapa la PP2A la li-enzyme.
PKA-Mediated phosphorylation ea subunit e laolang ea PP2A (PPP2R) e lebisa ho lokolloe ha PP2A ho HMGR, ho thibela dephosphorylation ea eona. Ka ho loantša litlamorao tsa glucagon le adrenaline, insulin e hlohlelletsa ho tlosoa ha phosphates ebe ka tsela eo e eketsa ts'ebetso ea HMGR.
Tekanyetso e eketsehileng ea HMGR e etsahala ka ho thibela maikutlo le k'holeseterole, hammoho le taolo ea motsoako oa eona ka ho eketsa boemo ba k'holeseterole ea intracellular le sterol.
Ketsahalo ena ea morao-rao e amahanngoa le ntho e ngotsoeng ea SREBP.
Ts'ebetso e joang 'meleng oa motho?
Ts'ebetso ea HMGR e boetse e beiloe leihlo ka ho saena le AMP. Keketseho ea cAMP e lebisa ts'ebetsong ea protheine ea cAMP e itšetlehileng ka CAMP. Sebakeng sa taolo ea HMGR, PKA phosphorylates subunit e laolang, e lebisang tokollong e eketsehang ea PP2A ho HMGR. Sena se thibela PP2A ho tlosa phosphates ho HMGR, ho thibela ts'ebetso ea eona hape.
Lelapa le leholo la protheine ea phosphatase e laolehang e laola le / kapa e thibela ts'ebetso ea li-phosphatase tse ngata, ho kenyelletsa le litho tsa malapa a PP1, PP2A, le PP2C. Ntle le phosphatase ea PP2A e ntšang phosphates ho AMPK le HMGR, li-phosphatase tsa lelapa la protheine phosphatase 2C (PP2C) le tsona li tlosa phosphates ho AMPK.
Ha melaoana ena e laola phosphorylate PKA, ts'ebetso ea li-phosphatase tse tlameletsoeng e fokotseha, e fella ka AMPK e setseng naheng ea phosphorylated le e sebetsang, le HMGR maemong a phosphorylated le a sa sebetseng. Ha ts'usumetso e tlosoa, e lebisa keketseho ea tlhahiso ea cAMP, boemo ba phosphorylation bo fokotseha, mme boemo ba dephosphorylation bo eketseha. Sephetho ke ho khutlela boemong bo phahameng ba ts'ebetso ea HMGR. Ka lehlakoreng le leng, insulin e lebisa ho fokotseha ha cAMP, ebe, e kenya ts'ebetso ea motsoako. Sephetho ke ho khutlela boemong bo phahameng ba ts'ebetso ea HMGR.
Ka lehlakoreng le leng, insulin e baka ho fokotseha ha cAMP, ka lehlakoreng le leng, e hlahisang ts'ebetso ea cholesterol. Sephetho ke ho khutlela boemong bo phahameng ba ts'ebetso ea HMGR. Insulin e lebisa ho fokotseha ha cAMP, eo, le eona e ka sebelisoang ho ntlafatsa ts'ebetso ea motsoako.
Bokhoni ba ho tsosa insulin le ho thibela glucagon, ts'ebetso ea HMGR e lumellana le tšusumetso ea lihormone tsena lits'ebetsong tse ling tsa metabolic metabolism. Mosebetsi oa mantlha oa li-hormone tsena tse peli ke ho laola ho fihlella le matla a ho tsamaisa lisele tsohle.
Taolo ea nako e telele ea mosebetsi oa HMGR e etsoa haholo-holo ka ho laola ho kopanngoa le ho senyeha ha enzyme. Ha maemo a cholesterol a phahame, boemo ba mofuta oa HMGR oa liphatsa tsa lefutso boa fokotseha, 'me ka lehlakoreng le leng, maemo a tlase a ts'ebetso ea mofuta oa gene.
Tlhahisoleseling ka k'holeseterole e fanoa ka video videong ena.
