Nws yog qhov tseem ceeb heev kom nkag siab txog qhov kev sib txuas ntawm cov cholesterol hauv lub siab tshwm sim. Yog hais tias koj xyuas qhov teeb meem no nyob rau hauv kom meej, nws yuav tam sim ntawd kom meej li cas piv lub siab muaj rau no organic compound. Tab sis ua ntej koj yuav tsum tau rov qab hais tias cov tshuaj tseem muaj lub npe, uas kuj tseem siv, namely roj.
Raws li tau hais tseg saum toj saud, cov khoom no yog cov organic sib txuas thiab pom nyob hauv txhua yam muaj sia. Nws yog ib qho tseem ceeb ntawm lipids.
Qhov siab tshaj plaws tau pom nyob hauv cov khoom ntawm tsiaj keeb kwm. Tab sis nyob rau hauv cov khoom cog muaj tsuas yog ib feem me me ntawm cov khoom sib xyaw no.
Nws kuj tseem ceeb kom nco ntsoov qhov tseeb tias nrog rau cov khoom noj tsuas yog 20 feem pua ntawm cov nyiaj ntawm cov roj cholesterol nkag mus, ntxiv 80 feem pua ntawm lub cev tsim tawm ntawm nws tus kheej. Los ntawm txoj kev, ntawm tag nrho cov tshuaj synthesized ib leeg, 50% yog tsim ncaj qha hauv daim siab. Qhov no tshwm sim nyob rau qib ntawm qib, qhov tshuav 30% yog tsim hauv cov hnyuv thiab tawv nqaij.
Tib neeg lub cev muaj ntau yam ntawm cov khoom no. Nyob rau tib lub sijhawm, nws yuav tsum raug sau tseg tias nws yog qhov system hematopoietic uas tau xoob nrog cov khoom siv no. Cov roj (cholesterol) hauv cov ntshav yog ib feem ntawm cov khoom sib txuas ua ke uas muaj protein, cov khoom zoo li no hu ua lipoproteins.
Complexes tuaj yeem muaj ob hom:
- HDL - muaj qhov ceev heev, lawv hu ua qhov zoo;
- LDL - muaj qhov tsawg kawg, cov tshuaj no hu ua qhov tsis zoo.
Nws yog hom thib ob uas nqa khoom txaus ntshai rau tib neeg. Tom qab lawv cov nag lossis daus, uas muaj cov kua muag ntawm cov tshuaj, lawv pib nthuav tawm hauv daim ntawv ntawm cov quav hniav rau ntawm phab ntsa ntawm cov hlab ntsha ntawm cov ntshav khov hauv lub zog, ua lub luag haujlwm thauj ntshav. Raws li qhov tshwm sim, txoj kev no dhau los ua qhov kev txhim kho hauv lub cev ntawm cov kab mob pathology li atherosclerosis.
Qhov kev nce qib ntawm atherosclerosis ua rau txoj kev txhim kho ntawm ntau yam kab mob hnyav.
Yooj yim sib txuas nta
Raws li tau hais los saum no, cov khoom siv no tuaj yeem muaj txiaj ntsig rau tib neeg, tau kawg, tsuas yog tias peb tab tom tham txog HDL.
Raws li qhov no, nws tau pom tseeb tias qhov kev lees paub tias cov roj (cholesterol) tiag tiag ua rau tib neeg ua yuam kev.
Cov roj (cholesterol) yog ua los ntawm cov roj ntsha:
- koom nrog kev sib tov ntawm cov tshuaj hormones poj niam txiv neej;
- ua kom muaj kev ua haujlwm ntawm serotonin receptors hauv lub hlwb;
- yog cov khoom tseem ceeb ntawm cov kua tsib, nrog rau cov vitamin D, uas yog lub luag haujlwm rau kev nqus ntawm cov rog;
- tiv thaiv cov txheej txheem ntawm kev rhuav tshem ntawm intracellular qauv nyob rau hauv tus ntawm dawb radicals.
Tab sis nrog rau cov khoom muaj txiaj ntsig zoo, cov tshuaj yeeb tshuaj tuaj yeem muaj kev puas tsuaj rau tib neeg kev noj qab haus huv. Piv txwv li, LDL tuaj yeem ua rau kev txhim kho ntawm cov kab mob loj, feem ntau pab txhawb kev txhim kho atherosclerosis.
Hauv daim siab, biocomponent yog hluavtaws sib xyaw ua ke hauv HMG lub zog rov qab. Qhov no yog qhov tseem ceeb enzyme koom nrog biosynthesis. Kev txwv tsis pub coj ua tshwm sim nyob rau hauv tus neeg ntawm kev tsis zoo.
Cov txheej txheem ntawm kev sib txuas ntawm ib yam khoom hauv lub siab muaj qhov tsis sib luag nrog kev txhaj tshuaj ntawm cov tshuaj sib txuas uas nkag mus rau tib neeg lub cev nrog zaub mov.
Txawm tias yooj yim dua, txoj kev no tau piav qhia li no. Lub siab ua ywj siab tswj cov qib roj cholesterol. Qhov ntau dua ib tus neeg noj cov khoom noj uas muaj cov khoom siv no, cov tshuaj tsawg dua yog tsim nyob rau hauv cov kab mob ntawm cov khoom hauv lub cev, thiab yog tias peb coj mus rau hauv cov nyiaj uas cov rog tau noj ua ke nrog cov khoom uas muaj nws, ces txoj kev cai no tseem ceeb heev.
Nta ntawm cov synthesis ntawm teeb meem
Cov neeg laus noj qab nyob zoo coj ua ke HDL ntawm tus nqi kwv yees li 1 g / hnub thiab haus kwv yees li 0.3 g / hnub.
Qib feem ntawm cov roj (cholesterol) hauv cov ntshav muaj cov nqi ntawd - 150-200 mg / dl. Tswj tau feem ntau los ntawm kev tswj qib ntawm kev coj ua ntawm denovo.
Nws yog ib qho tseem ceeb kom nco ntsoov tias cov synthesis ntawm HDL thiab LDL ntawm cov keeb kwm endogenous yog ib feem los ntawm kev noj haus.
Cov roj (cholesterol), ob leeg los ntawm cov khoom noj thiab tsim tawm hauv daim siab, yog siv rau hauv kev tsim cov qog ua xua, hauv kev sib txuas ntawm cov tshuaj hormones steroid thiab cov kua tsib kua qaub. Kev faib tawm ntau tshaj plaws yog siv hauv qhov kev sib txuas ntawm cov kua qaub.
Kev nqus ntawm HDL thiab LDL los ntawm cov hlwb tau tswj hwm nyob rau theem ruaj khov los ntawm peb qhov sib txawv:
- Kev tswj hwm ntawm HMGR Cov Haujlwm
- Kev cai ntawm cov rog tshaj tshaj uas tso ntshav dawb tsis txaus los ntawm kev ua si ntawm O-acyltransferase sterol, SOAT1 thiab SOAT2 nrog SOAT2, uas yog qhov tseem ceeb hauv kev ua haujlwm hauv lub siab. Kev tsim ua thawj zaug rau cov enzymes no yog ACAT rau acyl-CoA: cov roj ntsha acyltransferase. Cov Enzymes ACAT, ACAT1, thiab ACAT2 yog acetyl CoA acetyltransferases 1 thiab 2.
- Los ntawm kev tswj cov ntshav roj ntshav ntau ntau los ntawm LDL-mediated receptor uptake thiab HDL-mediated kev thauj rov qab.
Kev tswj hwm ntawm HMGR cov haujlwm yog qhov pib txhais tau ntawm kev tswj hwm qib ntawm biosynthesis ntawm LDL thiab HDL.
Lub enzyme yog tshuaj los ntawm plaub qhov sib txawv:
- cov tswv yim inhibition;
- tswj kev qhia ntawm noob;
- enzyme degradation tus nqi;
- phosphorylation-dephosphorylation.
Thawj peb txoj kev tswj hwm ua kom ncaj qha rau cov tshuaj yeeb yam ntawm nws tus kheej. Cov roj (cholesterol) ua raws li cov lus tawm rov qab ua haujlwm nrog HMGR uas twb muaj lawm thiab tseem ua rau lub cev enzyme sai sai. Qhov tom kawg yog los ntawm polyubiquitilation ntawm HMGR thiab nws cov kev ua haujlwm hauv cov qub pov tseg. Qhov peev xwm no yog qhov muaj txiaj ntsig ntawm thaj chaw sterol-rhiab ntawm HMGR SSD.
Ntxiv rau, thaum cov roj (cholesterol) ntau dhau, cov mRNA rau HMGR txo qis vim qhov cov noob hauv lub cev txo qis.
Cov Enzymes muab kev koom tes hauv cov khoom cua
Yog hais tias tus exogenous tivthaiv yog tswj hwm los ntawm covalent kev hloov kho, txoj kev ua no yuav raug coj los ntawm phosphorylation thiab dephosphorylation.
Lub enzyme tseem nquag nyob hauv daim ntawv tsis siv neeg. Phosphorylation ntawm lub enzyme txo nws txoj haujlwm.
HMGR yog phosphorylated los ntawm AMP-ua kom muaj protein kinase, AMPK. AMPK nws tus kheej tau qhib kho los ntawm phosphorylation.
AMPK phosphorylation yog catalyzed los ntawm tsawg kawg yog ob lub enzymes, uas yog:
- Lub luag haujlwm kinase ua lub luag haujlwm rau AMPK ua kom LKB1 (mob siab kinase B1). LKB1 tau pom thawj zaug hais tias yog tus noob hauv tib neeg muaj tus kabmob autosomal hloov pauv ntawm Putz-Jegers syndrome, PJS. LKB1 kuj tseem pom tias muaj cov kab mob ua qog hauv pulmonary adenocarcinoma.
- Qhov thib ob phosphorylating enzyme AMPK yog calmodulin-muaj protein kinase kinase beta (CaMKKβ). CaMKKβ induces AMPK phosphorylation teb rau kev nce ntxiv ntawm intracellular Ca2 + uas ua rau cov leeg mob.
Kev cai tswj hwm HMGR los ntawm cov kev hloov pauv cov tso cai tso cai HDL tsim tawm. HMGR yog nquag tshaj plaws nyob rau hauv xeev dephosphorylated. Phosphorylation (Ser872) yog catalyzed los ntawm AMP-ua kom muaj protein kinase (AMPK) enzyme, cov haujlwm uas tseem tau tswj hwm los ntawm phosphorylation.
Phosphorylation ntawm AMPK tuaj yeem tshwm sim vim tsawg kawg yog ob lub enzymes:
- LKB1;
- CaMKKβ.
Dephosphorylation ntawm HMGR, rov qab mus rau lub xeev ua haujlwm ntau, yog nqa los ntawm kev ua si ntawm cov protein phosphatases ntawm 2A tsev neeg. Cov kab ntawv no tso cai rau koj los tswj cov khoom lag luam HDL.
Dab tsi cuam tshuam rau hom roj (cholesterol)?
Muaj nuj nqi PP2A tshwm sim nyob rau hauv ob qhov sib txawv catalytic isoforms encoded los ntawm ob tus noob pom tias yog PPP2CA thiab PPP2CB. Ob lub ntsiab isoforms ntawm PP2A yog qhov heterodimeric core enzyme thiab heterotrimeric holoenzyme.
Lub zog tseem ceeb PP2A muaj lub pob scaffold substrate (thaum xub thawj hu ua A subunit) thiab catalytic subunit (C subunit). Lub catalytic α subunit raug kaw los ntawm PPP2CA noob, thiab lub catalytic β subunit raug kaw los ntawm PPP2CB noob.
Kev hloov kho ntawm aff scaffold yog nkag los ntawm PPP2R1A gene thiab and qhov xa tawm los ntawm PPP2R1B noob. Lub enzyme lub ntsiab, PP2A, cuam tshuam nrog kev hloov pauv qhov tsis paub meej kom sib sau ua ke rau hauv holoenzyme.
Lub chaw tswj hwm PP2A suav nrog plaub tsev neeg (keeb kwm hu ua B-subunits), txhua tus ntawm muaj ntau isoforms encoded los ntawm cov noob sib txawv.
Tam sim no, muaj 15 lub noob sib txawv rau cov kev cai tswj hwm ntawm PP2A B. Lub luag haujlwm tseem ceeb ntawm cov kev cai tswj hwm ntawm PP2A yog txhawm rau phosphorylated substrate protein rau phosphatase kev ua ntawm catalytic subunits ntawm PP2A.
PPP2R yog ib qho ntawm 15 qhov sib txawv tswj kev tso cai ntawm PP2A. Cov tshuaj hormones xws li glucagon thiab adrenaline cuam tshuam rau cov roj ntsha biosynthesis los ntawm kev ua haujlwm ntau ntxiv ntawm cov cai tswj fwm PP2A cov tsev neeg.
PKA-mediated phosphorylation ntawm qhov kev cai tswj hwm ntawm PP2A (PPP2R) ua rau muaj kev tso tawm ntawm PP2A los ntawm HMGR, tiv thaiv nws cov dephosphorylation. Los ntawm kev tiv thaiv kev cuam tshuam ntawm glucagon thiab adrenaline, insulin txhawb qhov kev tshem tawm ntawm phosphates thiab yog li nce qhov haujlwm ntawm HMGR.
Kev cai ntxiv ntawm HMGR tshwm sim los ntawm kev txwv tsis pub cov lus qhia nrog cov roj cholesterol, nrog rau cov cai ntawm nws cov khoom sib txuas los ntawm kev nce qib hauv cov roj (cholesterol) thiab sterol.
Qhov tshwm sim tom qab no cuam tshuam nrog qhov hloov pauv ntawm SREBP.
Tus txheej txheem nyob hauv tib neeg lub cev li cas?
HMGR kev ua haujlwm ntxiv yog saib ntxiv los ntawm kev piav qhia nrog AMP. Kev nce qib ntawm cAMP ua rau kev ua kom muaj cAMP-protein protein kinase, PKA. Hauv cov ntsiab lus ntawm HMGR cov kev cai, PKA phosphorylates cov kev cai tswj fwm, uas ua rau muaj kev tso tawm ntau ntawm PP2A los ntawm HMGR. Qhov no tiv thaiv PP2A tshem tawm cov phosphates los ntawm HMGR, tiv thaiv nws cov tshuaj ua kom rov qab los.
Ib tsev neeg loj ntawm cov tswj hwm protein phosphatase subunits tswj hwm thiab / lossis thaiv qhov kev ua si ntawm ntau cov phosphatases, suav nrog cov tswv cuab ntawm PP1, PP2A, thiab PP2C tsev neeg. Ntxiv rau PP2A phosphatases uas tshem phosphates ntawm AMPK thiab HMGR, phosphatases ntawm cov protein phosphatase 2C tsev neeg (PP2C) kuj tshem tawm phosphates los ntawm AMPK.
Thaum cov kev cai tswj fwm no phosphorylate PKA, qhov kev ua ntawm khi phosphatases poob qis, ua rau AMPK tseem tshuav nyob hauv phosphorylated thiab nquag xeev, thiab HMGR hauv lub phosphorylated thiab lub xeev tsis muaj zog. Raws li qhov kev tawm dag tawm tshem tawm, ua rau muaj qhov nce ntawm cAMP ntau lawm, qib phosphorylation tsawg zuj zus, thiab qib dephosphorylation nce ntxiv. Qhov kawg tshwm sim yog qhov rov qab mus rau qib siab dua ntawm HMGR kev ua haujlwm. Ntawm qhov tod tes, cov tshuaj insulin ua rau txo qis hauv CAMP, uas, nyeg, ua kom lub zog sib txuas. Qhov kawg tshwm sim yog qhov rov qab mus rau qib siab dua ntawm HMGR kev ua haujlwm.
Ntawm qhov tod tes, cov tshuaj insulin ua rau txo qis hauv CAMP, uas, nyeg, ua kom muaj zog cov roj (synthesis). Qhov kawg tshwm sim yog qhov rov qab mus rau qib siab dua ntawm HMGR kev ua haujlwm. Cov tshuaj Insulin ua rau txo qis hauv CAMP, uas, nyeg, tuaj yeem siv los txhim kho cov txheej txheem coj los ua ke.
Lub peev xwm los txhawb lub zog insulin thiab inhibit glucagon, HMGR kev ua haujlwm yog sib luag nrog kev cuam tshuam ntawm cov tshuaj hormones no rau lwm cov txheej txheem kev zom zaub mov. Lub luag haujlwm tseem ceeb ntawm ob cov tshuaj hormones no yog kom tswj tau kev nkag mus thiab thauj lub zog rau txhua lub hlwb.
Kev tswj mus sij hawm ntev ntawm HMGR cov haujlwm yog ua ntau los ntawm kev tswj cov synthesis thiab degradation ntawm cov enzyme. Thaum cov roj (cholesterol) nce siab, cov qib ntawm HMGR lub noob qhia txo qis, thiab kev hloov pauv, cov qib qis ua kom muaj kev sib txuas lus ntawm cov noob.
Cov ntaub ntawv ntawm cov cholesterol yog muab nyob rau hauv cov yeeb yaj kiab hauv tsab xov xwm no.
