Kubaluleke kakhulu ukuqonda ukuthi ukwakheka kwe-cholesterol esibindini kwenzeka kanjani. Uma uhlola kabanzi le ndaba, kuzocaca ukuthi isibindi sihlobana kanjani nale nhlanganisela yezinto eziphilayo. Kepha okokuqala udinga ukukhumbula ukuthi into nayo inebizo, elivame ukusetshenziswa, okungukuthi i-cholesterol.
Njengoba sekuphawuliwe ngenhla, lo muthi uyikhompiyutha ebunjiwe futhi uyatholakala kuzo zonke izinto eziphilayo. Kuyingxenye ebalulekile ye-lipids.
Ukuhlushwa okuphakeme kakhulu kuyabonakala emikhiqizweni yezilwane. Kepha emikhiqizweni yezitshalo kunengxenye encane yale khompiyutha.
Kubalulekile futhi ukuqaphela iqiniso lokuthi ngokudla kungamaphesenti angama-20 kuphela e-cholesterol engena, amaphesenti 80 asele umzimba ukhiqiza ngokuzimela. Ngendlela, yawo wonke umuthi owenziwe wedwa, ama-50% akhiwa ngqo esibindini. Lokhu kwenzeka ezingeni lamaselula, ama-30% asele akhiqizwa emathunjini nasesikhunjeni.
Umzimba womuntu uqukethe izinhlobo eziningana zale ngxenye. Ngasikhathi sinye, kufanele kuqashelwe ukuthi yi-hematopoietic system egcwele lokhu. I-cholesterol esegazini iyingxenye yezakhi eziyinkimbinkimbi ezinamaprotheni, izakhi ezinjalo zibizwa ngokuthi ama-lipoprotein.
Izinkimbinkimbi zingaba izinhlobo ezimbili:
- I-HDL - ine-density ephezulu kakhulu, ibizwa ngokuthi ilungile;
- I-LDL - inabantu abaphansi, lezi zinto zibizwa zimbi.
Kuluhlobo lwesibili oluthwala ingozi kubantu. Ngemuva kokuba sebekhethiwe, okubandakanya amakristalu ento leyo, baqala ukuqongelela ngohlobo lwama-plaque odongeni lwemithambo yegazi yesistimu yokujikeleza, inesibopho sokuhambisa igazi. Ngenxa yalokho, le nqubo iba imbangela yokuthuthuka emzimbeni we-pathology efana ne-atherosulinosis.
Ukuthuthuka kwe-atherosclerosis kuholela ekuthuthukisweni kwezifo eziningi ezimbi.
Izici zokuxhuma eziyisisekelo
Njengoba kushiwo ngenhla, lo mbala ungaba usizo kubantu, kusobala, kuphela uma sikhuluma nge-HDL.
Ngokusekelwe kulokhu, kuyacaca ukuthi ukugomela ukuthi i-cholesterol iyingozi ngokuphelele kubantu kuyiphutha.
I-cholesterol ekubeni yingxenye yokusebenza kwezinto eziphilayo:
- ubamba iqhaza ekwakhiweni kwama-hormone ocansi;
- iqinisekisa ukusebenza okujwayelekile kwama-serotonin receptors ebuchosheni;
- isakhi esiyinhloko se-bile, kanye novithamini D, obhekele ukumuncwa kwamafutha;
- ivimbela inqubo yokubhujiswa kwezakhiwo ze-intracellular ngaphansi kwethonya lama-radicals mahhala.
Kodwa ngokuhambisana nezakhiwo ezinhle, into ingayilimaza impilo yomuntu. Isibonelo, i-LDL ingadala ukuthuthukiswa kwezifo ezimbi, ngokuyinhloko inomthelela ekwakhiweni kwe-atherosclerosis.
Esibindini, i-biocomponent yenziwa ngaphansi kwethonya le-HMG redutase. Lesi yisibonakaliso esiyinhloko esibandakanyeka ku-biosynthesis. Ukuvinjwa kokuqamba kwenzeka ngaphansi kwethonya lezimpendulo ezingezinhle.
Inqubo yokuqamba kwento esibindini inobudlelwano obuhlukile nethamo lomuthi olungena emzimbeni womuntu ngokudla.
Noma kulula, le nqubo ichazwa ngale ndlela. Isibindi silawula ngokuzimela amazinga e-cholesterol. Lapho umuntu edla ukudla okuqukethe le ngxenye, kukhiqizwa into encane emangqamuzaneni esitho, futhi uma sinaka ukuthi amafutha adliwa kanye nemikhiqizo ekuqukethe, khona-ke le nqubo yokulawula ibaluleke kakhulu.
Izici zokwenziwa kwendaba
Abantu abadala abanempilo enhle bafaka i-HDL ngesilinganiso cishe esingu-1 g / ngosuku futhi badle cishe i-0,3 g / ngosuku.
Izinga le-cholesterol elingaguquki egazini linenani elinjalo - 150-200 mg / dl. Kugcinwe ikakhulukazi ngokulawula izinga lokuhlanganiswa kwe-denovo.
Kubalulekile ukuqaphela ukuthi ukwakheka kwe-HDL ne-LDL yemvelaphi yendabuko kulawulwa ngokwengxenye ngokudla.
I-cholesterol, yokudla nokuhlanganiswa kwesibindi, isetshenziswa ekwakheni ama-membranes, ekwakhiweni kwamahomoni e-steroid nama-bile acid. Ingxenye enkulu kakhulu yento isetshenzisiwe ekwakhekeni kwama-bile acid.
Ukudonswa kwe-HDL ne-LDL ngamaseli kugcinwa kusendaweni eqinile ngezindlela ezintathu ezihlukene:
- Ukulawulwa komsebenzi we-HMGR
- Ukulawulwa kwe-cholesterol yamahhala ye-intracellular ngokusebenzisa umsebenzi we-O-acyltransferase sterol, i-SOAT1 ne-SOAT2 ene-SOAT2, okuyingxenye esebenzayo yesibindi. Ukuqokwa kokuqala kwalezi enzymes kwakuyi-ACAT ye-acyl-CoA: acyltransferase cholesterol. Ama-Enzymes ACAT, ACAT1, ne-ACAT2 angama-acetyl CoA acetyltransferases 1 no-2.
- Ngokulawula amazinga we-cholesterol we-plasma ngokusebenzisa ukuthathwa kwe-receptor ye-LDL-Mediated kanye ne-HDL-mediated reverse transport.
Ukulawulwa komsebenzi we-HMGR kuyindlela eyinhloko yokulawula izinga le-biosynthesis ye-LDL ne-HDL.
I-enzyme ilawulwa ngamasu amane ahlukene:
- ukuvimbela impendulo
- Ukulawulwa kwesakhi sofuzo;
- isilinganiso sokucekelwa phansi kwe-enzyme;
- phosphorylation-dephosphorylation.
Izinqubo zokuqala ezintathu zokulawula zisebenza ngqo kuzinto ngokwazo. I-cholesterol isebenza njenge-inhibitor yempendulo ene-HMGR yangaphambilini ekhona futhi ibangela nokuwohloka okusheshayo kwe-enzyme. Lokhu kokugcina kungumphumela we-polyubiquitilation ye-HMGR kanye nokuwohloka kwayo ku-proteinosome. Leli khono lingumphumela wesizinda esibucayi se-sterol se-HMGR SSD.
Ngaphezu kwalokho, lapho i-cholesterol idlula ngokweqile, inani le-mRNA le-HMGR lehla ngenxa yokuncipha kwesakhi sofuzo.
Enzymes abathintekayo synthesis
Uma isakhi esingaphandle silawulwa ngokuguqulwa okubonakalayo, le nqubo izokwenziwa ngenxa ye-phosphorylation kanye ne-dephosphorylation.
I-enzyme isebenza kakhulu ngefomu elingafakwanga. Iphosphorylation ye-enzyme yehlisa umsebenzi wayo.
I-HMGR iphosphorylated yi-AMP-activated protein kinase, AMPK. I-AMPK uqobo icushiwe yi-phosphorylation.
I-phosphorylation ye-AMPK ikhubazeka okungenani ngama-enzyme amabili, okuyi:
- I-kinase eyinhloko ebhekele ukusebenza kwe-AMPK yi-LKB1 (isibindi kinase B1). I-LKB1 yaqala ukukhonjwa njengezakhi zofuzo kubantu eziphethe i-autosomal control mutation in Putz-Jegers syndrome, PJS. I-LKB1 nayo itholakala njenge-mutant ku-adenocarcinoma ye-pulmonary.
- I-AMPK yesibili ye-phosphorylating ye-phosphorylating i-proteinodase -aseaseaseaseaseaseaseasecyase (CaMKKβ). I-CaMKKβ ingenisa i-phosphorylation ye-AMPK ekuphenduleni kokunyuka kwe-Ca2 + ye-intracellular ngenxa yokuqunjelwa kwemisipha.
Ukulawulwa kwe-HMGR ngokuguqulwa okuvumelanayo kuvumela ukuthi i-HDL ikhiqizwe. I-HMGR isebenza kakhulu kusimo se-dephosphorylated. I-Phosphorylation (Ser872) idalwe i-enzyme ye-AMP-activated protein kinase (AMPK), umsebenzi wayo ulawulwa wuphosphorylation.
I-phosphorylation ye-AMPK ingavela okungenani ngama-enzyme amabili:
- I-LKB1;
- I-CaMKKβ.
I-Dephosphorylation ye-HMGR, ukuyibuyisela esimweni esisebenza ngokwengeziwe, kwenziwa ngomsebenzi wama-protein phosphatases womndeni we-2A. Lokhu kulandelana kukuvumela ukuthi ulawule ukukhiqizwa kwe-HDL.
Yini ethinta uhlobo lwe-cholesterol?
I-PP2A yokusebenza isebenza kuma-isoforms amabili ahlukile wokufunda afakwe ezinhlini ezimbili ezikhonjwe njenge-PPP2CA ne-PPP2CB. Ama-isoforms amabili amakhulu we-PP2A yi-heterodimeric core enzyme ne-heterotrimeric holoenzyme.
I-PP2A ephambili ye-enzyme iqukethe i-scaffold substrate (ekuqaleni ebizwa ngokuthi yi-subunit) ne-catalytic subunit (C subunit). I-catunic α subunit ifakiwe uhlobo lwe-PPP2CA, kanti i-catunic β subunit ifakiwe uhlobo lwe-PPP2CB.
Ukufakwa kwesisulu se-α kufakwe kuhlobo lwe-PPP2R1A kanye ne-β subunit nguhlobo lwe-PPP2R1B. I-enzyme enkulu, i-PP2A, ixhumana ne-subunit yokulawula eguqukayo ukuze bahlangane kwi-holoenzyme.
Izitho zokulawula ze-PP2A zibandakanya imindeni emine (ekuqaleni ebizwa ngokuthi yi-B-subunits), ngayinye equkethe ama-isoform amaningana afakwe ezinhlakeni ezihlukile.
Njengamanje, kunezinhlobo ezi-15 ezahlukahlukene zohlobo olungaphansi lwe-PP2A B. Umsebenzi oyinhloko wokuhambisa okungaphansi kwe-PP2A ukuqondisa amaprotheni asezingeni eliphansi emisebenzini ye-phosphatase yezinhlaka ezinkulukazi ze-PP2A.
I-PPP2R ingesinye sezingu-15 zokulawulwa okuhlukile kwe-PP2A. Ama-hormone afana ne-glucagon ne-adrenaline ayithinta kabi i-cholesterol biosynthesis ngokwandisa umsebenzi wokuzithoba okukhethekile komndeni we-enzyme we-PP2A.
I-phosphorylation ye-PKA-Mediated ye-subunit yokulawula ye-PP2A (PPP2R) iholela ekukhishweni kwe-PP2A kusuka ku-HMGR, ukuvimbela ukwehla kwayo. Ngokulwa nemiphumela ye-glucagon ne-adrenaline, i-insulin ivuselela ukususwa kwama-phosphates futhi ngaleyo ndlela yandise umsebenzi we-HMGR.
Ukulawulwa okwengeziwe kwe-HMGR kwenzeka ngokuvimbela impendulo nge-cholesterol, kanye nokulawulwa kokuhlanganiswa kwayo ngokwandisa izinga le-cholesterol ye-intracellular ne-sterol.
Le nto yakamuva ihlotshaniswa ne-transcript factor SREBP.
Inqubo injani emzimbeni womuntu?
Umsebenzi we-HMGR ubhekwa ngokwengeziwe ngokuvunyelwa nge-AMP. Ukwanda kwe-cAMP kuholela ekusebenzeni kwe-cAMP-protein proteinaseasease, PKA. Ngokwesimo somthethonqubo we-HMGR, i-PKA phosphorylates subunit yokulawula, okuholela ekukhulisweni okwandisiwe kwe-PP2A ku-HMGR. Lokhu kuvimbela i-PP2A ekususeni ama-phosphates ku-HMGR, kuvimbela ukwenziwa kwayo kabusha.
Umndeni omkhulu we-phosphatase olandelwayo ophathekayo ulawula futhi / noma uvimbela umsebenzi wama-phosphatases amaningi, kufaka phakathi amalungu emindeni ye-PP1, PP2A, ne-PP2C. Ngaphezu kwama-phosphatases we-PP2A, asusa ama-phosphates e-AMPK kanye ne-HMGR, ama-phosphatases omndeni we-protein we-phosphatase 2C (PP2C) nawo asusa ama-phosphates ku-AMPK.
Lapho lokhu okulawula kufaka i-phosphorylate PKA, umsebenzi wama-phosphatases aboshiwe uyancipha, okuphumela ku-AMPK okusele esifundeni se-phosphorylated futhi esisebenzayo, kanye ne-HMGR esifundeni se-phosphorylated nesingasebenzi. Lapho isikhuthazo sisuswa, okuholela ekukhuleni kokukhiqizwa kwe-cAMP, izinga le-phosphorylation lehla, futhi izinga le-dephosphorylation liyakhuphuka. Umphumela wokuphela ukubuyela ezingeni eliphakeme lomsebenzi we-HMGR. Ngakolunye uhlangothi, i-insulin iholela ekunciphiseni kwe-cAMP, okuthi, futhi kusebenze ukucubungula. Umphumela wokuphela ukubuyela ezingeni eliphakeme lomsebenzi we-HMGR.
Ngakolunye uhlangothi, i-insulin iholela ekunciphiseni kwe-cAMP, yona, futhi, isebenze synthesis cholesterol. Umphumela wokuphela ukubuyela ezingeni eliphakeme lomsebenzi we-HMGR. I-insulin iholela ekunciphiseni kwe-cAMP, yona, engasetshenziswa ukuthuthukisa inqubo yokuqamba.
Amandla okuvuselela i-insulin nokuvimbela i-glucagon, umsebenzi we-HMGR uhambisana nethonya lalawa ma-hormone kwezinye izinqubo ze-metabolic metabolic. Umsebenzi ophambili walawa ma-hormone amabili ukulawula ukufinyeleleka namandla okuhambisa kuwo wonke amaseli.
Ukulawulwa kwesikhathi eside komsebenzi we-HMGR kwenziwa ikakhulu ngokulawula ukwakheka nokudilizwa kwe-enzyme. Lapho amazinga e-cholesterol ephezulu, izinga le-HMGR gene expression lincipha, futhi, ngaphendle, amazinga aphansi kusebenze ukuveza uhlobo.
Imininingwane nge-cholesterol inikezwe kuvidiyo ekulesi sihloko.
