Kev tswj ntawm cov roj hluavtaws synthesis

Cov tshuaj tiv thaiv kab mob ua kom sib xyaw

2. Khoom cua ntawm isopentenyl diphosphate. Nyob rau theem no, peb phosphate seem muab txuas nrog mevalonic acid, tom qab ntawd nws yog decarboxylated thiab dehydrogenated.

3. Tom qab muab sib txuas nrog peb lub lev ntawm isopentenyl diphosphate, farnesyl diphosphate tau muab tso ua ke.

4. Qhov kev sib txuas ntawm squalene tshwm sim thaum ob qho kev farnesyl diphosphate seem ua txhua yam.

5. Tom qab cov kev rov ua dua, linear squalene caij mus lanosterol.

6. Kev tshem tawm ntawm cov pab pawg methyl ntau dhau, kev kho kom rov qab thiab isomerization ntawm cov roj molecule ua rau cov tsos ntawm cov cholesterol.

Kev cai ntawm kev ua ntawm hydroxymethylglutaryl-S-CoA reductase

3. Tus nqi ntawm cov roj zais zis roj biosynthesis tseem nyob ntawm kev saib xyuas cov cab kuj muaj protein ntaumuab rau cov khi thiab thauj ntawm hydrophobic intermediate synthesis metabolites.

Koj tuaj yeem nug lossis tawm koj lub tswvyim.

Lub ntsiab lus tseem ceeb ntawm kev tswj hwm yog qhov tshwm sim ntawm kev tsim cov mevalonic acid.

1. Txhua yam kev cai tswjfwm. Cov roj (cholesterol), thiab hauv lub siab - thiab cov kua tsib yog cov tshuaj tiv thaiv HMG-CoA reductase.

2. Kev tsuj tawm ntawm cov khoom cua ntawm HMG-CoA reductase cov roj (cholesterol).

3. Kev tswj los ntawm phosphorylation-dephosphorylation ntawm HMG-CoA reductase, cov neeg tsis muaj phosphorylated daim ntawv. Glucagon ua rau lub cev tsis ua haujlwm, thiab insulin ua rau kom ua kom muaj kev cuam tshuam los ntawm cov nyom. Yog li, tus nqi ntawm cov roj hluavtaws sib xyaw ua ke hloov pauv nrog kev hloov pauv hauv xeev thiab postabsorption tiv thaiv.

4. Tus nqi ua ke ntawm HMG-CoA reductase nyob rau hauv lub siab yog qhov tseeb ua rau tsis nco qab qhov phom sij: qhov siab tshaj thaum ib tag hmo, thiab tsawg kawg thaum sawv ntxov.

Roj ester pauv

Hauv cov kabmob cov cholesterol esterification tshwm sim thaum raug acyl-CoA-cholesterol-acyltransferase (AHAT):

Acyl-CoA + Cov Roj (Cholesterol) ® NS-CoA + Acylcholesterol

Hauv cov hlwb, feem ntau linoleylcholesterol yog tsim. Esters pom feem ntau hauv cov cytosol uas yog ib feem ntawm lipid mob. Kev tsim cov esters tuaj yeem xav txog, ntawm ib sab, ua ib qho kev ua kom tshem tawm cov roj (cholesterol) ntau dua ntawm cov qog ua pa, thiab ntawm qhov tod tes, yog cov txheej txheem rau khaws cov roj hauv lub cev. Kev nthuav dav ntawm cov peev xwm tshwm sim nrog kev koom tes ntawm enzymes esterasehydrolyzing cov roj cholesterol esters:

Acylcholesterol + H₂O atty Fatty Acid + Roj Cholesterol

Cov tshuaj synthesis thiab hydrolysis ntawm esters yog tshwj xeeb tshaj yog nyob hauv cov hlwb ntawm adrenal cortex.

Hauv cov ntshav lipoproteins ester tsim tshwm sim nrog kev koom tes ntawm lecithin-cholesterol-acyltransferase (LHAT), ua kom muaj qhov hloov chaw ntawm qhov tsis haum los ntawm lecithin rau roj. LHAT yog tsim nyob rau hauv daim siab, zais rau hauv cov hlab ntshav thiab txuas rau lipoproteins. LHAT nquag tshaj plaws hauv HDL, qhov chaw nws yog ib cheeb tsam hauv txheej txheej saum npoo av. Cov roj (esters) cov roj uas tsim los ntawm no yog hydrophobic thiab raus hauv lipid core. Hauv cov phospholipid monolayer, muaj qhov chaw seem rau cov roj (cholesterol), uas tuaj yeem muaj cov roj (cholesterol) los ntawm cov cell lossis los ntawm lwm cov lipoproteins. Yog li, HDL zoo nkaus li yog qhov ua rau chob siab vim yog qhov kev nqis tes ua ntawm LHAT.

Bile Acid Khoom cua

Hauv lub siab, ib feem ntawm cov roj cholesterol tau hloov mus rau hauv cov kua tsib kua qaub. Cov kua tsib cov kua qaub yuav suav tau tias yog derivatives ntawm cholanic acid. Cholanic acid yog li ntawd tsis yog tsim hauv lub cev. Hauv cov kab mob hepatocytes los ntawm cov roj (cholesterol), thawj cov kua tsib kua qaub yog tsim - chenodeoxycholic thiab cholicCov. Tom qab tso tawm ntawm cov kua tsib mus rau hauv txoj hnyuv hauv qab qhov kev txiav txim siab ntawm enzymes ntawm lub plab hnyuv muaj, cov kab mob thib ob cov kua tsib yog tsim los ntawm lawv - lithocholic thiab deoxycholicCov. Lawv nqus los ntawm cov hnyuv, nrog cov ntshav ntawm lub portal vein nkag mus rau lub siab, thiab tom qab ntawd ces mus rau hauv cov kab tsib. Bile muaj cov roj ntsha ua ke nrog cov kua qaub, i.e., lawv cov khoom sib txuas nrog glycine lossis taurine. Qhov concentration ntawm cov kua tsib kua tsib hauv cov kua tsib yog li 1%.

Lub ntsiab ntawm cov kua tsib kua qaub yog koom nrog hepatoenteric ncig.Ib feem me me ntawm cov kua tsib kua qaub - li 0.5 g ib hnub - yog tawm hauv cov quav. Qhov no tau them nyiaj los ntawm kev sib txuas ntawm cov kua tsib cov kua qaub tshiab hauv daim siab, bile acid nyiaj yuav hloov kho nyob hauv thaj tsam li 10 hnub.

Cov roj (cholesterol) los kuj tseem nyob hauv cov hnyuv. Nws nkag mus rau hauv cov hnyuv nrog zaub mov thiab los ntawm daim siab ua ib feem ntawm bile. Cov cholesterol mus rau hauv cov ntshav muaj cov feem los ntawm cov kua tsib (endogenous cov cholesterolsynthesized hauv lub siab), thiab cov feem tau los ntawm cov khoom noj (exogenous cov cholesterol) Kev tshem tawm cov cholesterol los ntawm cov ntaub so ntswg tshwm sim los ntawm nws cov oxidation mus rau cov kua tsib hauv cov nplooj siab hauv lub siab, tom qab ntawd lawv cov quav nrog cov quav (kwv yees li 0.5 g ib hnub) thiab los ntawm kev zam ntawm cov roj uas tsis hloov pauv (tseem nrog quav).

Nyob hauv lub xeev nyob ruaj ruaj:

(Cholesterol)_kawg + Mob khaub thuas_ex) - (Cov Cholesterol)_excre + Kua tsib kua qaub_excre) = 0

Yog tias qhov sib npaug no tsis sib haum xeeb, cov concentration ntawm cov roj (cholesterol) hauv cov ntaub so ntswg thiab hauv cov ntshav pauv. Muaj feem pua ​​ntshav - hypercholesterolemiaCov. Qhov no nce ntxiv ntawm kev pheej hmoo ntawm atherosclerosis thiab mob gallstone.

LAM HAIS TXOG TXOJ CAI REGULATION

Lipid metabolism yog tswj los ntawm nruab nrab lub paj hlwb. Ntev ntev kev xav tsis zoo zoo siab, nce ntxiv hauv kev tso tawm cov catecholamines rau hauv cov hlab ntshav tuaj yeem ua rau pom hnyav poob. Nkaus glucagon ntawm cov lipolytic system zoo ib yam li kev txiav txim ntawm catecholamines.

Adrenaline thiab norepinephrine nce kev ua si ntawm cov nqaij lipase thiab tus nqi ntawm lipolysis nyob rau hauv adipose nqaij, vim li ntawd, cov ntsiab lus ntawm cov roj ntsha hauv cov ntshav plasma nce ntxiv.

Cov tshuaj insulin muaj qhov sib txawv ntawm adrenaline thiab glucagon ntawm lipolysis thiab kev sib sau ntawm cov roj ntsha.

Kev loj hlob lawm stimulates lipolysis, ntxias lub zog ntawm acenylate cyclase. Pituitary hypofunction ua rau kev tso tawm ntawm cov rog hauv lub cev (rog rog pituitary).

Thyroxine, cov tshuaj tiv thaiv kev sib deevkuj tseem cuam tshuam cov metabolism hauv lipid. Kev tshem tawm cov qog ua plees ua yi hauv cov tsiaj ua rau cov rog ntau dua.

LIPID TXAUV TXHUA YAM

Cov roj (cholesterol) yog cov tshuaj steroid tshwj xeeb rau cov tsiaj muaj sia. Qhov chaw tseem ceeb ntawm nws tsim nyob rau hauv tib neeg lub cev yog daim siab, qhov 50% ntawm cov cholesterol yog synthesized, 15-20% yog tsim nyob rau hauv txoj hnyuv me, qhov seem yog synthesized hauv daim tawv nqaij, adrenal cortex thiab gonads. Cov peev txheej ntawm kev tsim ntawm cov nyiaj cholesterol thiab cov hauv kev ntawm nws cov kev siv nyiaj tau nthuav tawm hauv Daim Duab 22.1.

Daim duab. 22.1. Kev tsim thiab faib tawm cov roj (cholesterol) hauv lub cev.

Cov roj (cholesterol) hauv tib neeg lub cev (tag nrho cov nyiaj tau txog 140 g) tuaj yeem raug faib muab faib rau peb pas dej:

30 g), hloov pauv sai, muaj cov roj cholesterol ntawm lub plab hnyuv phab ntsa, ntshav ntshav, kab mob siab thiab lwm yam plab hnyuv siab raum, rov ua dua tshiab hauv 30 hnub (1 g / hnub),

50 g), maj mam hloov cov roj (cholesterol) ntawm lwm cov plab hnyuv siab raum thiab cov ntaub so ntswg,

60 g), cov roj qeeb mentshis hloov pauv ntawm txha caj qaum thiab paj hlwb, cov ntaub so ntswg sib txuas, qhov hloov tshiab tau muab xam rau xyoo.

Qhov synthesis ntawm cov roj cholesterol tshwm sim hauv cytosol ntawm cov hlwb. Qhov no yog ib qho ntawm cov kev coj noj coj ua ntev tshaj plaws hauv tib neeg lub cev. Nws tau nce mus rau hauv 3 theem: thawj zaug xaus nrog kev tsim mevalonic acid, qhov thib ob nrog kev tsim cov squalene (linear hydrocarbon qauv muaj txog 30 carbon atoms). Thaum lub sijhawm peb theem, squalene pauv mus rau lanosterol lwg me me, tom qab ntawv muaj txog 20 qhov kev hloov tshwm sim uas tau hloov lanosterol los ua cov rog.

Hauv qee cov ntaub so ntswg, hydroxyl pab pawg ntawm cov roj (cholesterol) esterifies los ua esters. Cov tshuaj tiv thaiv yog catalyzed los ntawm intracellular enzyme AHAT (acylCoA: cholesterol acyltransferase). Qhov tshuaj tiv thaiv esterification tseem tshwm sim hauv cov ntshav hauv HDL, qhov chaw uas muaj lub enzyme LHAT (lecithin: cholesterol acyltransferase) nyob. Cholesterol esters yog daim ntawv uas nws thauj los ntawm ntshav los yog muab tso rau hauv cov hlwb. Hauv cov ntshav, kwv yees li 75% ntawm cov roj (cholesterol) nyob hauv daim ntawv esters.

Cov roj ntsha ua kom sib xyaw yog tswj hwm los ntawm kev cuam tshuam rau cov haujlwm thiab qhov ntau ntawm qhov tseem ceeb ntawm cov txheej txheem - 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase).

Qhov no yog ua tau los ntawm ob txoj kev:

1. Phosphorylation / dephosphorylation ntawm HMG-CoA reductase. Cov tshuaj Insulin stimulates lub dephosphorylation ntawm HMG-CoA reductase, yog li txhais nws mus rau hauv lub xeev nquag. Yog li ntawd, nyob rau lub sijhawm nqus, qhov kev sib txuas ntawm cov cholesterol nce ntxiv. Nyob rau lub sijhawm no, qhov muaj los ntawm qhov pib substrate rau cov khoom cua, acetyl-CoA, kuj tseem nce ntxiv. Glucagon muaj qhov sib txawv: los ntawm cov protein kinase A, nws txhawb lub phosphorylation ntawm HMG-CoA reductase, tig mus rau hauv lub xeev tsis muaj zog. Raws li qhov tshwm sim, cov hluavtaws sib xyaw ua ke ntawm cov roj ntsha tom qab lub sijhawm postabsorption thiab thaum lub sijhawm yoo mov yog txwv.

2. Kev txwv ntawm kev coj ua ntawm HMG-CoA reductase.Cov pa roj (cov khoom lag luam kawg ntawm cov khoom noj metabolic) txo qhov hloov pauv ntawm HMG-CoA reductase gene, yog li inhibiting nws tus kheej synthesis, thiab cov kua tsib cov kua qaub kuj ua rau zoo li qub.

Kev nqa cov ntshav hauv cov ntshav yog nqa tawm ua ib feem ntawm qhov tshuaj. LPs muab cov roj (exogenous cholesterol) hauv cov ntaub so ntswg, txiav txim siab nws cov ntws tawm hauv nruab nrog cev thiab kev tawm mus los ntawm lub cev. Cov roj (cholesterol) Exogenous raug xa mus rau lub siab ua ib feem ntawm cov khoom ChM. Muaj, ua ke nrog cov roj synthesized endogenous, nws tsim cov nyiaj ib txwm. Hauv cov tshuaj hepatocytes, TAGs thiab cov roj cholesterol yog ntim rau hauv VLDL, thiab hauv daim ntawv no tau muab zais rau hauv cov ntshav. Hauv cov ntshav, VLDL nyob rau hauv qhov kev nqis tes ntawm LP-lipase, uas hydrolyzes TAG rau glycerol thiab fatty acids, yog thawj hloov ua LSPP, thiab tom qab ntawd mus rau LDL uas muaj txog 55% ntawm cov roj cholesterol thiab nws cov esters. LDL yog qhov tseem ceeb thauj cov roj (cholesterol) hauv cov roj uas nws xa mus rau cov nqaij (70% ntawm cov roj cholesterol thiab nws cov esters hauv cov ntshav yog ib feem ntawm LDL). LDL los ntawm cov ntshav nkag mus rau hauv lub siab (nce txog 75%) thiab lwm cov ntaub so ntswg uas muaj LDL receptors nyob rau lawv qhov chaw.

Yog hais tias tus nqi ntawm cov cholesterol mus rau hauv lub cell ntau tshaj qhov nws xav tau, ces kev sib txuas ntawm LDL receptors yog suppress, uas txo cov kev khiav ntawm cov cholesterol los ntawm cov ntshav. Nrog ib qho kev poob qis hauv kev saib xyuas ntawm cov roj cholesterol dawb hauv lub cell, ntawm qhov tsis sib xws, receptor synthes yog qhib kom ua huaj. Cov tshuaj hormones yog koom nrog cov kev cai ntawm LDL receptor synthesis: cov tshuaj insulin, triiodothyronine thiab cov txiv neej pw ua ke tsim cov receptors, thiab glucocorticoids txo.

Hauv kev sib "caj ces rov qab los thauj", i.e. txoj hauv kev uas xyuas kom rov qab los ntawm cov roj khov rau daim siab, HDL ua lub luag haujlwm tseem ceeb. Lawv tau sib sau ua ke rau hauv daim siab ua daim ntawv ntawm cov tsis paub ua ntej uas xyaum siv tsis muaj roj thiab TAG. HDL cov txheej txheem ua ntej hauv cov ntshav yog khov nrog cov roj cholesterol, tau txais los ntawm lwm LPs thiab cov cell ua raws. Qhov hloov chaw ntawm cov cholesterol mus rau HDL cuam tshuam LHAT cov enzyme nyob rau lawv thaj chaw. Qhov enzyme no txuas cov roj fatty acid residue los ntawm phosphatidylcholine (lecithin) rau cov roj (cholesterol). Raws li qhov tshwm sim, hydrophobic molecule ntawm cov roj cholesterol ester yog tsim, uas txav rau sab hauv HDL. Yog li, tsis txhob haus cawv HDL, ntxiv nrog cov roj cholesterol, tig mus rau hauv HDL 3 - kev loj hlob thiab qhov loj me. HDL 3 sib pauv roj esters rau TAG uas muaj nyob hauv VLDL thiab STD nrog kev koom tes ntawm cov protein tshwj xeeb uas hloov cov roj cholesterol ntawm lipoproteins. Hauv qhov xwm txheej no, HDL 3 tig mus rau hauv HDL2, qhov loj me uas nce ntxiv vim muaj kev txuam nrog TAG. VLDL thiab STDL nyob rau hauv lub zog ntawm LP-lipase tau hloov pauv mus rau LDL, uas feem ntau xa cov roj cholesterol mus rau lub siab. Ib feem me me ntawm cov roj cholesterol yog xa mus rau lub siab ntawm HDL2 thiab HDL.

Synthesis ntawm cov kua tsib kua qaub. Hauv daim siab, 500-700 mg ntawm bile acids nyob rau hauv ib hnub yog tsim los ntawm cov cholesterol. Lawv tsim muaj cov tshuaj tiv thaiv ntawm kev qhia ntawm hydroxyl pawg nrog kev koom nrog ntawm hydroxylases thiab cov tshuaj tiv thaiv ntawm qee qhov oxidation ntawm cov saw sab ntawm cov roj (daim duab 22.2):

Daim duab. 22.2. Txheej txheem ntawm kev tsim ntawm cov kua tsib kua qaub.

Thawj cov tshuaj tiv thaiv hluav taws xob - qhov tsim ntawm 7-a-hydroxycholesterol - yog txoj cai. Cov kev ua ntawm cov enzyme uas catalyzes cov tshuaj tiv thaiv no yog inhibited los ntawm qhov kawg khoom ntawm txoj hauv kev, kab mob kua qaub. Lwm cov kev cai tswj hwm tshuab yog phosphorylation / dephosphorylation ntawm cov enzyme (phosphorylated daim ntawv ntawm 7-a-hydroxylase yog ua haujlwm). Kev cai kuj tseem tuaj yeem hloov los ntawm qhov hloov pauv ntawm lub cev: cov roj hauv ntshav ua kom hloov pauv ntawm 7-a-hydroxylase gene, thiab cov kua tsib cov kua tsib. Cov thyroid hormones txaus rau kev sib sau ntawm 7-a-hydroxylase, thiab kev tshaj tawm estrogen. Xws li cov nyhuv ntawm cov tshuaj estrogen ntawm cov kev sib txuas ntawm cov kua tsib kua qaub piav qhia yog vim li cas tus kab mob gallstone tshwm sim rau cov poj niam 3-4 zaug ntau dua li cov txiv neej.

Cholic thiab chenodeoxycholic acids tsim los ntawm cov roj (cholesterol) yog hu ua “cov kua tsib cov kua qaub”. Feem ntau ntawm cov kua qaub no ua ke nrog kev sib txuas - ntxiv ntawm glycine lossis taurine lwg me me rau carboxyl pawg ntawm cov kua tsib cov kua qaub. Kev sib xyaw pib nrog kev tsim ntawm kev ua kom nquag plias ntawm cov kua tsib kua qaub - derivatives ntawm CoA, tom qab ntawd taurine lossis glycine tau muab txuas, thiab vim li ntawd 4 ntau yam kev sib txuas tau tsim: taurocholic thiab taurohenodeoxycholic, glycocholic thiab glycohenodeoxycholic acids. Lawv yog cov muaj zog emulsifiers ntau dua li cov kua tsib kua qaub dhau los. Conjugates nrog glycine yog tsim 3 zaug ntau dua li nrog taurine, txij li thaum tus nqi ntawm taurine hauv lub cev tsawg. Hauv txoj hnyuv, qhov me me ntawm cov khoom sib txuas ua ke ntawm thawj cov kua tsib kua qaub hauv kev ua haujlwm ntawm cov kab mob enzymes tau hloov mus ua cov kab mob kua qaub thib ob. Deoxycholic acid, tsim los ntawm cholic, thiab lithocholic, tsim los ntawm deoxycholic, tsis tshua muaj soluble thiab maj mam nqus ntau hauv cov hnyuv.

Kwv yees 95% ntawm cov kua tsib kua qaub uas nkag mus rau txoj hnyuv rov qab rau daim siab los ntawm lub vev portal, ces rov muab zais rau hauv cov kua tsib thiab rov siv rau hauv emulsification cov rog. Txoj hau kev ntawm cov kua tsib yog kua hu ua enterohepatic ncig. Nrog kev quav, cov kua tsib muaj kua feem ntau yog muab tshem tawm.

Gallstone muaj tus kab mob (cholelithiasis) yog txheej txheem pathological nyob rau hauv cov pob zeb tsim hauv lub zais plab, hauv paus ntawm uas yog cov roj (cholesterol).

Kev tso tawm ntawm cov roj cholesterol mus rau hauv cov kua tsib yuav tsum muaj nrog kev tso tawm kom sib npaug ntawm cov kua tsib kua qaub thiab phospholipids uas ua kom hydrophobic cov roj cholesterol nyob hauv lub xeev micellar. Cov laj thawj uas ua rau muaj qhov hloov ntawm qhov sib piv ntawm cov kua tsib kua roj thiab cov roj (cholesterol) hauv cov kua tsib yog: zaub mov nplua nuj hauv cov roj cholesterol, khoom noj khoom haus muaj roj ntau ntau, stagnation ntawm cov kua tsib hauv lub zais plab, ua kom tsis muaj zog nkag mus rau hauv lub cev, tsis hnov ​​lus ntawm cov kua tsib cov kua qaub, kab mob gallbladder.

Hauv feem ntau cov neeg mob uas muaj cholelithiasis, kev sib xyaw ntawm cov cholesterol yog nce ntxiv, thiab cov lus sib txuas ntawm cov kua tsib yog los ntawm nws qeeb qeeb, uas ua rau muaj qhov tsis sib luag ntawm cov roj thiab cov kua tsib cov kua qaub zais rau hauv cov kua tsib. Raws li qhov tshwm sim, cov roj (cholesterol) pib ua rau cov kem plab hauv qhov txhab, ua rau khov khov ua nthwv dej uas maj mam tawv. Qee zaum nws yog impregnated nrog bilirubin, cov nqaijrog thiab ntsev calcium. Cov pob zeb tsuas yog muaj cov roj (cov roj cholesterol) lossis cov roj (cholesterol), bilirubin, cov protein thiab calcium. Cov pob zeb roj hauv pob zeb feem ntau yog dawb, thiab cov pob zeb sib xyaw ua ke yog xim av nyob rau qhov sib txawv.

Hauv thawj theem ntawm pob zeb tsim, chenodeoxycholic acid tuaj yeem siv los ua tshuaj. Ib zaug nyob rau hauv lub zais khoom, nws maj mam yaj lub pob zeb hauv roj, tab sis qhov no yog qhov txheej txheem qeeb uas kav ntev ntau lub hlis.

Atherosclerosis yog kab mob pathology uas pom los ntawm cov tsos mob tshwm sim ntawm atherogenic plaques rau sab hauv ntawm vascular phab ntsa. Ib qho ntawm cov laj thawj tseem ceeb rau kev txhim kho ntawm cov kab mob no yog kev ua txhaum ntawm qhov sib txig sib luag ntawm kev noj cov roj cholesterol los ntawm cov khoom noj, nws cov synthesis thiab excretion los ntawm lub cev. Cov neeg mob uas mob atherosclerosis tau txhawb nqa ntau LDL thiab VLDL ntau. Muaj kev cuam tshuam ntawm kev sib xyaw ntawm HDL concentration thiab qhov nyiam ntawm kev txhim kho atherosclerosis. Qhov no yog raws li lub tswv yim ntawm kev ua haujlwm ntawm LDL raws li cov neeg nqa cov roj (cholesterol) hauv cov ntaub so ntswg, thiab HDL los ntawm cov ntaub so ntswg.

Qhov yooj yim metabolic "yuav tsum tau ua ntej" rau kev txhim kho atherosclerosis yog hypercholesterolemia. (cov roj ntsha hauv cov ntshav).

Hypercholesterolemia tsim:

1. vim muaj cov roj (cholesterol) ntau dhau, cov carbohydrates thiab cov rog,

2. lub caj ces tsis tseem ceeb ua rau muaj kev tiv thaiv kab mob tsis zoo hauv cov qauv ntawm LDL lossis apoB-100 receptors, ntxiv rau cov tshuaj tiv thaiv kab mob ntau ntxiv lossis tso pa tawm ntawm apoB-100 (nyob rau hauv tsev neeg muaj kev sib koom ua ke hyperlipidemia, nyob rau hauv cov ntshav ntau thiab cov roj (cholesterol) thiab TAG thiab cov ntshav nce siab).

Lub luag haujlwm tseem ceeb hauv cov txheej txheem ntawm kev txhim kho atherosclerosis yog ua si los ntawm kev hloov kho tshuaj. Kev hloov pauv ntawm cov qauv qub ntawm lipids thiab cov protein nyob hauv LDL ua rau lawv txawv teb chaws rau lub cev thiab yog li muaj ntau qhov nkag rau ntes los ntawm phagocytes.

Kev hloov kho tshuaj tuaj yeem tshwm sim los ntawm ntau cov txheej txheem:

1. glycosylation ntawm cov protein uas tshwm sim thaum cov concentration ntawm cov piam thaj hauv cov ntshav nce ntxiv,

2. peroxide kev hloov kho, ua rau muaj kev hloov pauv hauv lipids hauv lipoproteins thiab cov qauv ntawm apoB-100,

3. qhov tsim ntawm autoimmune complex ntawm LP-cov tshuaj tiv thaiv (hloov cov tshuaj tuaj yeem ua rau kev tsim kho autoantibodies).

Hloov LDL yog nqus los ntawm macrophages. Tus txheej txheem no tsis tswj hwm los ntawm tus nqi ntawm cov roj (cholesterol) uas nqus tau, vim tias nws nkag mus rau hauv cov hlwb los ntawm cov kev txais tshwj xeeb, yog li macrophages tau dhau mus nrog cov roj (cholesterol) thiab tig mus rau hauv "cov hlwb ua npuas" uas nkag mus rau hauv qhov chaw subendothelial. Qhov no ua rau muaj qhov tsim ntawm lipid me ntsis lossis ib daim hlab hauv cov phab ntsa ntawm cov hlab ntsha. Nyob rau theem no, viav endothelium tuaj yeem tuav nws cov qauv. Nrog rau kev nce hauv cov xov tooj ntawm cov npuas dej, muaj kev puas tsuaj endothelial tshwm sim. Kev puas tsuaj ua rau platelet ua haujlwm. Raws li qhov tshwm sim, lawv tau zais thromboxane, uas ua rau platelet sib sau, thiab tseem pib tsim cov platelet kev loj hlob tau, uas ua rau muaj kev cuam tshuam loj ntawm cov leeg hlwb. Cov yav tom ntej tsiv tawm los ntawm medial mus rau sab hauv txheej ntawm phab ntsa arterial, yog li pab txhawb kev loj hlob ntawm cov quav hniav. Ntxiv mus, cov quav hniav tawm nrog cov nqaij hauv lub cev, cov hlwb ua hauv daim nyias nyias yog necrotic, thiab cov roj (cholesterol) yog tso rau hauv qhov chaw intercellular. Hauv cov theem kawg ntawm txoj kev loj hlob, cov quav hniav yog impregnated nrog ntsev ntsev thiab ua kom tuab heev. Hauv thaj chaw ntawm cov quav hniav, ntshav txhaws feem ntau tsim, thaiv cov lumen ntawm lub nkoj, uas ua rau muaj kev cuam tshuam loj heev hauv cov nqaij hauv qhov chaw sib txuas thiab txhim kho lub plawv nres.

Txoj cai ntawm kev ua ke ntawm cov roj (cholesterol) - nws cov enzyme tseem ceeb (HMG-CoA reductase) yog ua raws ntau txoj hauv kev.

Phosphorylation / dephosphorylation ntawm HMG reductase. Nrog kev nce ntxiv ntawm cov insulin / glucagon piv, cov enzyme phosphorylates thiab dhau mus rau hauv ib lub xeev muaj txiaj ntsig. Kev ua ntawm cov tshuaj insulin yog ua tiav los ntawm 2 enzymes.

HMG-CoA reductase kinase phosphatase, uas hloov lub kinase rau hauv qhov chaw tsis muaj zog dephosphorylated:

Phosphotase HMG-CoA reductase los ntawm kev hloov nws mus rau hauv lub xeev dephosphorylated nquag. Qhov tshwm sim ntawm kev tawm tsam no yog qhov tsim ntawm dephosphorylated active daim ntawv ntawm HMG-CoA reductase.

Yog li ntawd, lub sijhawm nqus, cov roj cholesterol nce ntxiv. Nyob rau lub sijhawm no, qhov muaj nyob rau ntawm thawj txheej txheej zuj zus rau kev sib sau ntawm cov cholesterol - acetyl - CoA nce ntxiv (vim los ntawm kev noj zaub mov muaj cov carbohydrates thiab cov rog, txij li CoA acetyl tau tsim thaum lub sijhawm piam thaj thiab cov roj nyeem).

Hauv lub xeev postabsorbent, glucagon los ntawm proteingenase A stimulates phosphorylation ntawm HMG - CoA - reductase, tig mus rau hauv lub xeev tsis muaj zog. Qhov kev ua no tau txhim kho los ntawm qhov tseeb tias tib lub sijhawm glucagon ua rau lub zog phosphorylation thiab kev tsis muaj phosphotase ntawm HMG-CoA reductase, yog li ua kom HMG-CoA reductase nyob rau hauv lub phosphorylated inactive state. Raws li qhov tshwm sim, cov hluavtaws sib xyaw ua ke nyob rau hauv lub sijhawm postabsorption thiab thaum lub sijhawm yoo mov yog inhibited los ntawm endogenous synthesis. Yog tias cov roj (cholesterol) cov ntsiab lus hauv cov khoom noj tau coj mus rau 2%, tom qab ntawd cov synthesis ntawm cov roj (endogenous cholesterol) poob qis. Tab sis kev ua tiav ntawm kev ua tiav ntawm cov cholesterol synthesis tsis tshwm sim.

Qhov theem ntawm inhibition of cholesterol biosynthesis nyob rau hauv kev cuam tshuam ntawm cov cholesterol los ntawm cov khoom noj nws txawv ntawm ib tus neeg. Qhov no qhia tau tias tus kheej ntawm tus txheej txheem ntawm kev tsim cov roj cholesterol. Los ntawm kev txo qhov sib ntawm cov roj (synthesis), nws muaj peev xwm txo nws cov concentration hauv cov ntshav.

Yog tias qhov sib txig sib txig sib luag ntawm kev noj cov roj (cholesterol) nrog cov khoom noj thiab nws cov tshuaj nyob hauv lub cev ntawm ib sab tes thiab qhov kev tshem tawm ntawm cov kua tsib thiab cov roj (cholesterol) nyob rau lwm qhov tau tawg, cov concentration ntawm cov roj cholesterol hauv cov nqaij thiab ntshav pauv. Cov kev mob tshwm sim loj tshaj plaws yog cuam tshuam nrog kev nce ntshav hauv cov ntshav cov ntshav siab (hypercholesterolemia), thaum tseem muaj peev xwm txhim kho atherosclerosis thiab cholelithiasis nce.

Familial hypercholesterolemia (HCS) - daim ntawv no muaj ntau yam ntau - txog li 1 tus neeg mob ib 200 tus neeg. Cov kab mob uas tau txais keeb kwm hauv HCS yog qhov kev ua txhaum ntawm qhov nqus ntawm LDL los ntawm cov hlwb, thiab yog li ntawd, qhov txo qis hauv LDL catabolism. Raws li qhov tshwm sim, kev xav ntawm LDL hauv cov ntshav nce, ntxiv rau cov roj (cholesterol) vim tias nws muaj ntau hauv LDL. Yog li ntawd, nrog HCS, qhov kev tso cia ntawm cov cholesterol nyob hauv cov nqaij, tshwj xeeb hauv daim tawv nqaij (xanthomas), ntawm cov hlab ntsha yog cov yam ntxwv.

Kev txwv tsis pub coj los ua ke ntawm HMG-CoA reductase

Cov khoom kawg ntawm cov kev zom zaub mov ntawm cov roj (cholesterol). Nws txo qhov nqi ntawm kev hloov pauv ntawm HMG-CoA reductase noob, yog li inhibiting nws tus kheej synthesis. Lub siab ua haujlwm hnyav ua ke cov kua tsib kua qaub los ntawm cov roj cholesterol, thiab yog li cov kua tsib cov kua qaub ua rau cov kev ua haujlwm ntawm HMG-CoA reductase gene. Txij li HMG-CoA reductase tshwm sim tom qab ua ke ntawm kwv yees li 3, inhibition ntawm cov hluavtaws cov roj ntsha enzyme no yog ib txoj cai tswj tau zoo.