Ndikofunikira kumvetsetsa momwe kapangidwe ka cholesterol mu chiwindi chimachitikira. Ngati mupenda nkhaniyi mwatsatanetsatane, nthawi yomweyo zimveka kuti chiwindi chimakhala bwanji ndi chiwalochi. Koma choyamba muyenera kukumbukira kuti mankhwalawo amakhalanso ndi dzina, lomwe limagwiritsidwanso ntchito nthawi zambiri, lotchedwa cholesterol.
Monga taonera kale, chinthu ichi ndi chophatikiza ndipo chimapezeka m'zamoyo zonse. Ndi gawo lofunikira la lipids.
Kuzindikira kwakukulu kumawonekera pazinthu zachilengedwe. Koma pazomera zangomera pali gawo laling'ono laling'ono lomwe limapangidwa.
Ndikofunikanso kuzindikira kuti palimodzi ndi chakudya 20% yokha ya kuchuluka kwa cholesterol yomwe imalowera, 80 peresenti yotsala yomwe thupi limapanga palokha. Mwa njira, yathunthu yopanga yokha, 50% imapangidwa mwachindunji. Izi zimachitika pamaselo a cellular, 30% yotsalayo imapangidwa m'matumbo ndi pakhungu.
Thupi laumunthu lili ndi mitundu ingapo ya chinthuchi. Nthawi yomweyo, ziyenera kudziwika kuti ndi hematopoietic system yomwe imakhala ndi chinthu ichi. Cholesterol m'magazi ndi gawo la mankhwala osakanikirana ndi mapuloteni, ma protein amenewa amatchedwa lipoproteins.
Mavuto amatha kukhala amitundu iwiri:
- HDL - ali ndi kachulukidwe kwambiri, amatchedwa abwino;
- LDL - yokhala ndi kachulukidwe kakang'ono, zinthu izi zimatchedwa zoyipa.
Ndiwo mtundu wachiwiri womwe umabweretsa ngozi kwa anthu. Pambuyo povundukuka, yomwe imakhala ndi makhiristo amtunduwu, amayamba kudziunjikira ngati zipilala pazitseko zamitsempha yamagazi yamagazi, yoyendetsera magazi. Zotsatira zake, njirayi imakhala chifukwa cha chitukuko mu thupi la matenda monga atherosulinosis.
Kukula kwa atherosulinosis kumabweretsa chitukuko cha matenda ambiri oyipa.
Zinthu zoyanjanitsa
Monga tafotokozera pamwambapa, chinthu ichi chitha kukhala chothandiza kwa anthu, pokhapokha ngati tikulankhula za HDL.
Kutengera izi, zikuwonekeratu kuti kunena kuti cholesterol imavulaza anthu ndi cholakwika.
Cholesterol kukhala yogwira mtima:
- amatenga nawo gawo mu kapangidwe ka mahomoni ogonana;
- imawonetsetsa magwiridwe antchito a serotonin receptors mu ubongo;
- ndiye gawo lalikulu la bile, komanso vitamini D, womwe umayendetsa mafuta;
- imalepheretsa njira yowonongeka ya zigawo za intracellular mothandizidwa ndi ma free radicals.
Koma kuphatikiza pazabwino, thunthu limatha kuvulaza thanzi la munthu. Mwachitsanzo, LDL imatha kuyambitsa matenda akuluakulu, makamaka imathandizira pakukula kwa atherosulinosis.
Mu chiwindi, biocomponent imapangidwa mothandizidwa ndi HMG redutase. Iyi ndiye puloteni yofunika kwambiri yokhudzira biosynthesis. Kuletsa kwa kaphatikizidwe kumachitika mothandizidwa ndi mayankho olakwika.
Kapangidwe ka kapangidwe ka chinthu m'chiwindi kamayanjana ndi gawo la piritsi yomwe imalowa m'thupi la munthu ndi chakudya.
Ngakhale zosavuta, njirayi imafotokozedwa motere. Chiwindi chimadzilamulira moyenera mafuta a cholesterol. Munthu akamadya chakudya chokhala ndi chinthuchi, zinthu zochepa zimapangidwa m'maselo a chiwalocho, ndipo ngati tikuganizira kuti mafuta amadyedwa pamodzi ndi zinthu zomwe zili nacho, ndiye kuti njira yolamulirayi ndiyofunika kwambiri.
Mawonekedwe a kapangidwe kazinthu
Akuluakulu athanzi labwino amapanga HDL pamlingo pafupifupi 1 g / tsiku ndipo amadya pafupifupi 0,3 g / tsiku.
Mlingo wa cholesterol wosasintha m'magazi uli ndi mtengo wotere - 150-200 mg / dl. Imakonzedwa makamaka ndikuwongolera kukula kwa denovo.
Ndikofunikira kudziwa kuti kapangidwe ka HDL ndi LDL komwe amachokera kumayendetsedwa pang'ono ndi zakudya.
Cholesterol, yonse yochokera kuzakudya ndi zopangidwa m'chiwindi, imagwiritsidwa ntchito popanga zimitsemvu, kaphatikizidwe ka mahomoni a steroid ndi ma asidi a bile. Gawo lalikulu kwambiri la chinthucho limagwiritsidwa ntchito mu kapangidwe ka bile acid.
Kutenga kwa HDL ndi LDL ndi maselo kumayendetsedwa mosasintha machitidwe atatu osiyana:
- Kuwongolera kwa Ntchito ya HMGR
- Kuwongolera owonjezera intracellular free cholesterol kudzera mu ntchito ya O-acyltransferase sterol, SOAT1 ndi SOAT2 yomwe ili ndi SOAT2, yomwe ndiyo gawo loyambira kwambiri pachiwindi. Kapangidwe koyamba ka ma enzymes awa anali ACAT ya acyl-CoA: acyltransferase cholesterol. Enzymes ACAT, ACAT1, ndi ACAT2 ndi acetyl CoA acetyltransferase 1 ndi 2.
- Mwa kuwongolera kuchuluka kwa cholesterol ya plasma kudzera pakukweza ka LDL-mediated receptor ndi HDL-mediated reverse shipping.
Kuwongolera ntchito ya HMGR ndiyo njira yoyamba yolamulirira kuchuluka kwa biosynthesis ya LDL ndi HDL.
Enzyme imayendetsedwa ndi njira zinayi:
- mayankho enhibition;
- kuwongolera mawonekedwe amtundu;
- kuchuluka kwa kuchuluka kwa michere;
- phosphorylation-dephosphorylation.
Njira zitatu zoyambirira zimagwirira ntchito molunjika pazinthu zomwezi. Cholesterol imachita ngati yankho la inhibitor lomwe lili ndi HMGR yomwe ilipo ndipo limayambitsanso kufooka kwa enzyme. Zotsirizazo ndizotsatira za polyubiquitilation ya HMGR ndikuwonongeka kwake mu proteinosome. Kutha uku ndi chifukwa cha sterol-sensitive domain HMGR SSD.
Kuphatikiza apo, cholesterol ikachuluka, kuchuluka kwa mRNA kwa HMGR kumachepa chifukwa chakuchepa kwa majini.
Enzymes nawo synthesis
Ngati gawo lakunja likuyendetsedwa mwa kusinthanitsa kophatikizana, njirayi idzachitika chifukwa cha phosphorylation ndi dephosphorylation.
Enzyme imagwira ntchito kwambiri mosapangidwa. Phosphorylation ya enzyme imachepetsa ntchito yake.
HMGR ndi phosphorylated ndi AMP-activated protein kinase, AMPK. AMPK yokha imayendetsedwa ndi phosphorylation.
Phosphorylation ya AMPK imapangidwa ndi michere iwiri:
- Kinase yoyamba yomwe imayambitsa activation ya AMPK ndi LKB1 (chiwindi kinase B1). LKB1 idayamba kuzindikiridwa ngati majini mwa anthu omwe ali ndi kusintha kwadzikoli pamatenda a Putz-Jegers, PJS. LKB1 imapezekanso kuti imasinthasintha mu pulmonary adenocarcinoma.
- Phosphorylating enzyme AMPK yachiwiri ndi pulodulin wodalira mapuloteni kinase kinase beta (CaMKKβ). CaMKKβ imayambitsa phosphorylation ya AMPK poyankha kuwonjezeka kwa intracellular Ca2 + chifukwa cha kufupika kwa minofu.
Kuwongolera kwa HMGR posintha mwanjira ina kumathandizira kuti HDL ipangidwe. HMGR imagwira ntchito kwambiri mdziko la dephosphorylated. Phosphorylation (Ser872) imapangidwa ndi enzyme ya AMP-activated protein kinase (AMPK), ntchito yomwe imayendetsedwanso ndi phosphorylation.
Phosphorylation ya AMPK imatha kuchitika chifukwa cha michere iwiri:
- LKB1;
- CaMKKβ.
Dephosphorylation ya HMGR, ndikubwezeretsanso ku malo omwe amagwira ntchito kwambiri, amachitidwa kudzera mu zochita za mapuloteni a banja la 2A. Izi zikuthandizani kuti muwongolere kupanga kwa HDL.
Zomwe zimakhudza mtundu wa cholesterol?
Yogwira ntchito PP2A ilipo m'mitundu iwiri yosiyanasiyana isoforms yokhala ndi mitundu iwiri yotchulidwa PPP2CA ndi PPP2CB. Ma isoforms awiri akuluakulu a PP2A ndi heterodimeric core enzyme ndi heterotrimeric holoenzyme.
Enzyme yayikulu ya PP2A imakhala ndi gawo laling'ono (lomwe poyambirira limatchedwa A subunit) komanso chothandizira (C subunit). Mathandizowa othandizira í amalembeka ndi jini la PPP2CA, ndipo chothandizira cha "un subunit imasungidwa ndi mtundu wa PPP2CB.
Kukhazikitsidwa kwa í scaffold kumakhazikitsidwa ndi jini la PPP2R1A ndi β kugonjera ndi mtundu wa PPP2R1B. Enzyme yayikulu, PP2A, imalumikizana ndi subunit yoyendetsera yosunthika kuti ikasonkhane mu holoenzyme.
Magawo olamulira a PP2A amaphatikizapo mabanja anayi (omwe poyamba amatchedwa B-subunits), lirilonse lomwe lili ndi ma isoform angapo omwe amakhala ndi mitundu yosiyanasiyana.
Pakadali pano pali mitundu 15 yosiyanasiyana yoyang'anira mtundu wa PP2A B. Ntchito yayikulu yogwiritsira ntchito ma PP2A ndikuwunika mapuloteni a phosphorylated substrate kuntchito ya phosphatase yamphamvu zothandizira za PP2A.
PPP2R ndi amodzi mwa magawo 15 osiyanasiyana oyendetsera PP2A. Ma mahormone monga glucagon ndi adrenaline amakhudzanso cholesterol biosynthesis powonjezera zochitika zina zapadera za PP2A michere ya banja.
PKA-mediated phosphorylation ya regunit yovomerezeka ya PP2A (PPP2R) imatsogolera kutulutsidwa kwa PP2A ku HMGR, kuletsa dephosphorylation yake. Mwa kuthana ndi zovuta za glucagon ndi adrenaline, insulin imathandizira kuchotsedwa kwa phosphates ndipo potero amawonjezera ntchito ya HMGR.
Kuwongolera kowonjezera kwa HMGR kumachitika kudzera poletsa mayankho ndi cholesterol, komanso kuyang'anira kaphatikizidwe kake poonjezera kuchuluka kwa cholesterol ya intracellular ndi sterol.
Chochitika chotsirizachi chikugwirizana ndi cholembedwa cha SREBP.
Kodi machitidwe ali bwanji mthupi la munthu?
Ntchito za HMGR zimayang'aniridwa mwakuwonetsa ndi AMP. Kuwonjezeka kwa cAMP kumabweretsa kuyambitsa kwa cAMP-amadalira proteinasease, PKA. Potengera malamulo a HMGR, PKA phosphorylates subunit reguleit, yomwe imatsogolera kutulutsidwa kwakukulu kwa PP2A kuchokera ku HMGR. Izi zimalepheretsa PP2A kuchotsa ma phosphates ku HMGR, kulepheretsa kuyambiranso.
Banja lalikulu la mapuloteni othandizira phosphatase amagonjera amawongolera ndi / kapena amalepheretsa zochitika zama phosphatase ambiri, kuphatikizapo mamembala a PP1, PP2A, ndi mabanja a PP2C. Kuphatikiza pa ma phosphatases a PP2A, omwe amachotsa ma phosphates ku AMPK ndi HMGR, ma phosphatases a protein phosphatase 2C banja (PP2C) amachotsanso ma phosphates ku AMPK.
Maulamulowa akagonjera phosphorylate PKA, ntchito ya ma phosphatases womangidwa amachepa, zimapangitsa AMPK yotsalira mu boma la phosphorylated komanso yogwira, ndi HMGR mu phosphorylated komanso osagwira ntchito. Pamene kukondoweza kumachotsedwa, kutsogoza kuwonjezeka kwa kupanga kwa cAMP, kuchuluka kwa phosphorylation kumachepa, ndipo kuchuluka kwa dephosphorylation kumakulanso. Zotsatira zomaliza ndikubwerera pamwambamwamba wa zochitika za HMGR. Komabe, insulin imayambitsa kuchepa kwa cAMP, yomwe, imayambitsa kuphatikizika. Zotsatira zomaliza ndikubwerera pamwambamwamba wa zochitika za HMGR.
Komabe, insulin imayambitsa kuchepa kwa cAMP, pomwe, imayambitsa kuphatikiza cholesterol. Zotsatira zomaliza ndikubwerera pamwambamwamba wa zochitika za HMGR. Insulin imabweretsa kuchepa kwa cAMP, yomwe, imatha kugwiritsidwa ntchito kupititsa patsogolo kapangidwe kake.
Kuthekera kolimbikitsa insulin ndikuletsa glucagon, ntchito ya HMGR imagwirizana ndi mphamvu ya mahomoni awa pamachitidwe ena a metabolic metabolic. Ntchito yayikulu yamahomoni awiri awa ndikuwongolera kupezeka ndi kutumizira mphamvu kumaselo onse.
Kuwongolera kwanthawi yayitali kwa ntchito ya HMGR kumachitika makamaka ndikuwongolera kaphatikizidwe ndi kuwonongeka kwa enzyme. Mafuta a cholesterol akakhala apamwamba, kuchuluka kwa mawonekedwe a HMGR kumachepa, komanso, magulu otsika amathandizira kutanthauza kwa majini.
Zambiri pa cholesterol zimaperekedwa mu kanema munkhaniyi.
