Malangizo a cholesterol synthesis

Cholesterol synthesis reaction scheme

2. kaphatikizidwe ka isopentenyl diphosphate. Pakadali pano, zotsalira zitatu za phosphate zimaphatikizidwa ndi mevalonic acid, ndiye kuti imapangidwa ndi decarboxylated komanso dehydrogenated.

3. Pambuyo pophatikiza mamolekyulu atatu a isopentenyl diphosphate, farnesyl diphosphate imapangidwa.

4. Kuphatikizika kwa squalene kumachitika pamene zotsalira ziwiri za farnesyl diphosphate zimamangidwa.

5. Pambuyo pazochitikazo zovuta, mzere wa squalene umayenda mozungulira mpaka ku lanosterol.

6. Kuchotsa kwamagulu a methyl ochulukitsa, kubwezeretsa komanso kusokonekera kwa molekyulu kumabweretsa kuwoneka kwa cholesterol.

Kuongolera ntchito ya hydroxymethylglutaryl-S-CoA reductase

3. Kuchuluka kwa cholesterol biosynthesis kumadaliranso pamsasa mapuloteni enieni onyamulakupereka zomangamanga ndi zoyendera za hydrophobic apakatikati synthesis metabolites.

Mutha kufunsa kapena kusiya malingaliro anu.

Mfundo yayikulu pamalamulo ndi momwe mapangidwe a mevalonic acid.

1. Malangizo onse. Cholesterol, ndi chiwindi - ndi ma asidi a bile amalepheretsanso kuchepa kwa HMG-CoA.

2. Kutembenuka kwa kapangidwe ka cholesterol cha HMG-CoA reductase.

3. Malamulo a phosphorylation-dephosphorylation a HMG-CoA reductase, mawonekedwe osagwira phosphorylated. Glucagon imayambitsa kuchepa kwa magazi, ndipo insulin imayambitsa kutseguka kudzera mu zovuta zazomwe zimachitika. Chifukwa chake, kuchuluka kwa cholesterol kaphatikizidwe kumasintha ndi kusintha kwa kayendedwe ndi ma postabsorption.

4. Kuchulukitsa kwa kapangidwe ka kuchepa kwa HMG-CoA m'chiwindi kumatha kusinthasintha kwamkati: kuwonjezeka pakati pausiku, komanso kuchepera kwa m'mawa.

Kusintha kwa cholesterol ester

M'maselo cholesterol esterization kumachitika poululidwa acyl-CoA-cholesterol-acyltransferase (AHAT):

Acyl-CoA + Cholesterol ® NS-CoA + Acylcholesterol

M'maselo, makamaka linoleylcholesterol amapangidwa. Ma esters amapezeka makamaka mu cytosol monga gawo la milid ya m'malo. Kapangidwe ka ma esters kumatha kuganiziridwa, kumbali imodzi, ngati njira yochotsera cholesterol yochulukirapo kuzinthu zakumaso, komanso, ngati njira yosungira cholesterol mu cell. Kulimbikitsa kwa nkhokwe kumachitika ndi kutenga nawo gawo kwa ma enzymes zotupahydrolyzing cholesterol esters:

Acylcholesterol + N₂O ® Fatty Acid + Cholesterol

Kuphatikizika ndi hydrolysis ya esters imagwira ntchito makamaka mu ma cell a adrenal cortex.

M'magazi a lipoprotein Kupanga kwa ester kumachitika ndi kutenga nawo gawo lecithin-cholesterol-acyltransferase (LHAT), yomwe imapangitsa kuti ma acyl otsala akhale lecithin kupita ku cholesterol. LHAT imapangidwa m'chiwindi, imatulutsidwa m'magazi ndipo imaphatikizidwa ndi lipoproteins. LHAT yogwira ntchito kwambiri mu HDL, pomwe imasanjidwa pamtunda. Ma cholesterol esters omwe amapangidwa pano ndi hydrophobic ndikamizidwa mu lipid pachimake. Mu phospholipid monolayer, pamakhala mpata wa cholesterol, womwe umatha kudzazidwa ndi cholesterol kuchokera kumankhwala am'mimba kapena ma lipoprotein ena. Chifukwa chake, HDL imawoneka ngati msampha wa cholesterol chifukwa cha zomwe LHAT ikuchita.

Bile Acid kaphatikizidwe

Mu chiwindi, gawo la cholesterol limasinthidwa kukhala bile acid. Ma acid akhungu amatha kuthandizidwa kuti amachokera ku cholanic acid. Cholanic acid chotere sichimapangidwa mthupi. Mu hepatocytes ochokera ku cholesterol, ma asidi achilengedwe apakati amapangidwa - khaloku ndi cholic. Pambuyo katulutsidwe wa bile mu matumbo pansi pa zochita za michere ya m'mimba, maluwa am'mimba a bile amapangidwa kuchokera kwa iwo - mamembala ndi deoxycholic. Amatengedwa m'matumbo, ndimagazi amitsempha yama portal amalowa m'chiwindi, kenako kulowa mu ndulu. Bile imakhala makamaka ndi conjugated bile acid, i.e., omwe amaphatikiza ndi glycine kapena taurine. Kukumana kwa asidi acid mu bile ndi pafupifupi 1%.

Gawo lalikulu la bile acids limakhudzidwa hepatoenteric kufalitsidwa.Gawo laling'ono la bile acid - pafupifupi 0,5 g patsiku - limapukutidwa ndowe. Izi zimalipiridwa ndi kaphatikizidwe kazinthu zatsopano za bile mu chiwindi, thumba la bile acid limasinthidwa pafupifupi masiku 10.

Cholesterol imaphatikizidwanso makamaka m'matumbo. Imalowa m'matumbo ndi chakudya komanso kuchokera ku chiwindi monga gawo la bile. Cholesterol yemwe amaikidwa m'magazi amakhala ndi kachigawo kakang'ono kochokera ku bile (cholesterol cha amkatikapangidwe kake m'chiwindi), komanso kachigawo kamene kamachokera ku chakudya (kolesterolo wakunja) Kuchotsa cholesterol ku zimakhala kumachitika ndi makutidwe ndi okosijeni a bile mandimu m'chiwindi, kutsatiridwa ndi kuphipha kwawo ndowe (pafupifupi 0,5 g patsiku) ndikuchotseredwa kwa cholesterol yosasinthika (komanso ndowe).

Muli m'malo:

(Cholesterol_kutha + Cholesterol_ex) - (Cholesterol_chonde + Mafuta ma acid_chonde) = 0

Vutoli likasokonekera, kuchuluka kwa cholesterol m'misempha komanso m'magazi kumasintha. Kuchuluka kwa mafuta m'thupi - hypercholesterolemia. Izi zimawonjezera mwayi wa atherosulinosis ndi matenda a ndulu.

LIPID CHITSANZO CHOMALIZA

Lipid metabolism imayendetsedwa ndi dongosolo lamanjenje lamkati. Chokhalitsa kupsinjika kwa malingaliro, kuwonjezereka kwa kutulutsidwa kwa makatekolamaini m'magazi kungayambitse kuwonda kwambiri. Machitidwe glucagon pa lipolytic system ili yofanana ndi zochitika za katekisimu.

Adrenaline ndi norepinephrine kuwonjezera ntchito ya minofu lipase ndi kuchuluka kwa lipolysis mu adipose minofu, chifukwa, zomwe zimakhala zamafuta m'magazi amwazi zimakwera.

Insulin ali ndi zotsutsana ndi adrenaline ndi glucagon pa lipolysis ndi kukhathamiritsa mafuta acids.

Kukula kwamafuta imapangitsa lipolysis, kulimbikitsa kaphatikizidwe ka acenylate cyclase. Pituitary hypofunction imatsogolera kukuchokera kwa mafuta m'thupi (kunenepa kwambiri).

Thyroxine, mahomoni ogonanazimakhudzanso kagayidwe ka lipid. Kuchotsa tiziwalo togonana mu nyama kumayambitsa kuchuluka kwamafuta.

LIPID METABOLIC ZOTSATIRA

Cholesterol ndi steroid yokhudza mitundu ya nyama. Malo akuluakulu a mapangidwe ake m'thupi la munthu ndi chiwindi, pomwe 50% ya cholesterol imapangidwa, 1520% imapangidwa m'matumbo ang'onoang'ono, enawo amapangika pakhungu, adrenal cortex ndi gonads. Zomwe zimapangidwa pakupanga thumba la cholesterol ndi njira zomwe zimagwiritsidwira ntchito zikufotokozedwa mkuyu. 22.1.

Mkuyu. 22.1. Mapangidwe ndi kufalitsa kolesterol m'thupi.

Holesterol yathupi laumunthu (yonse yokwana pafupifupi 140 g) ikhoza kugawidwa m'madziwe atatu:

30 g), ikusinthika mwachangu, imakhala ndi cholesterol ya khoma lamatumbo, madzi a m'magazi, chiwindi ndi ziwalo zina za parenchymal, kukonzanso kumachitika masiku 30 (1 g / tsiku),

50 g), kusinthana pang'onopang'ono cholesterol ya ziwalo zina ndi minofu,

60 g), cholesterol yosinthika kwambiri ya msana ndi ubongo, minyewa yolumikizirana, kuchuluka kwa zosinthika kumawerengeredwa pazaka.

Kuphatikizika kwa cholesterol kumachitika mu cytosol yama cell. Iyi ndi njira imodzi yayitali kwambiri m'thupi la munthu. Amakhala m'magawo atatu: woyamba umatha ndi mapangidwe a mevalonic acid, wachiwiri ndikupanga squalene (mawonekedwe a hydrocarbon okhala ndi maatomu 30 a kaboni). Mu gawo lachitatu, squalene amasinthidwa kukhala molekyule ya lanosterol, ndiye pali zochitika 20 zotsatizana zomwe zimasinthira lanosterol kukhala cholesterol.

M'minyewa ina, gulu lama hydroxyl la cholesterol limapanga ma esters. Zomwe zimachitidwazo zimakhudzidwa ndi intracellular enzyme AHAT (acylCoA: cholesterol acyltransferase). Machitidwe a esterization amapezekanso m'magazi mu HDL, pomwe enzyme LHAT (lecithin: cholesterol acyltransferase) imapezeka. Ma cholembera a cholesterol ndi mawonekedwe omwe amayendetsedwa ndi magazi kapena kuyikidwa m'maselo. M'magazi, pafupifupi 75% ya cholesterol imakhala mu mawonekedwe a esters.

Kuphatikizika kwa Cholesterol kumayendetsedwa ndikumakhudza ntchito ndi kuchuluka kwa mapangidwe ofunikira - 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase).

Izi zimatheka m'njira ziwiri:

1. Phosphorylation / dephosphorylation of HMG-CoA reductase. Insulin imathandizira dephosphorylation ya HMG-CoA reductase, potero imawamasulira kukhala dziko logwira ntchito. Chifukwa chake, munthawi ya mayamwidwe, kaphatikizidwe wa cholesterol umachuluka. Munthawi imeneyi, kupezeka kwa gawo loyambira la kaphatikizidwe, acetyl-CoA, kumakulanso. Glucagon ili ndi zotsutsana nazo: kudzera mu proteinasease A, imathandizira phosphorylation ya HMG-CoA reductase, ndikusintha kukhala malo osagwira ntchito. Zotsatira zake, kuphatikiza kwa cholesterol mu nthawi ya postabsorption komanso pakusala kudya kumalepheretsa.

2. Kuletsa kapangidwe ka HMG-CoA reductase.Cholesterol (mapeto a njira ya metabolic) amachepetsa kusintha kwa mtundu wa HMG-CoA reductase, motero amalepheretsa kaphatikizidwe kake, ndipo ma asidi a bile amachititsanso chimodzimodzi.

Kutenga kwa cholesterol yamagazi kumachitika ngati gawo lamankhwala. LPs imapereka cholesterol yakunja mu minofu, kudziwa momwe imayendera pakati pa ziwalo ndi kutulutsa kuchokera m'thupi. Mafuta a cholesterol a m'magazi amaperekedwa ku chiwindi monga gawo la chan yotsalira ya ChM. Pamenepo, limodzi ndi mafuta amkati am'madzi, amapanga thumba limodzi. Mu hepatocytes, ma TAG ndi cholesterol amawaika mu VLDL, ndipo mwa njirayi amatsitsidwa m'magazi. Mothandizidwa ndi LP-lipase, hydrolyzing TAG kupita ku glycerol ndi acid acid m'magazi, ma VLDLPs amasinthidwa kukhala LSPPs kenako LDLPs okhala ndi 55% ya cholesterol ndi ma esters ake. LDL ndiyo njira yayikulu yoyendera ya cholesterol momwe imaperekedwera minyewa (70% ya cholesterol ndipo mafuta ake m'magazi ndi gawo la LDL). LDL yochokera m'mwazi imalowa m'chiwindi (mpaka 75%) ndi zimakhala zina zomwe zimakhala ndi LDL receptors pamwamba pawo.

Ngati kuchuluka kwa cholesterol yomwe ilowa mu cell kupitirira zosowa zake, ndiye kuti mapangidwe a LDL receptors amachepetsa, omwe amachepetsa mafuta a cholesterol kuchokera m'magazi. Ndi kuchepa kwa kuchuluka kwa cholesterol yaulere mu cell, m'malo mwake, kuphatikiza kwa receptor kumayendetsedwa. Mahomoni amatenga nawo gawo pakayendetsedwe ka LDL receptor kaphatikizidwe: insulin, triiodothyronine ndi mahomoni ogonana amalimbikitsa mapangidwe a receptors, ndipo glucocorticoids amatsika.

Mu mayendedwe omwe amatchedwa "cholesterol kurudi transport", i.e. njira yomwe imatsimikizira kubwerera kwa cholesterol ku chiwindi, HDL imachita gawo lalikulu. Amapangidwa m'chiwindi mu mawonekedwe am'mbuyomu omwe samakhala ndi cholesterol ndi TAG. HDL oyambilira m'magazi amadzaza ndi cholesterol, amawalandira kuchokera ku ma LPs ena ndi ma membrane a ma cell. Kusamutsidwa kwa cholesterol kupita ku HDL kumaphatikizapo enzyme ya LHAT yomwe ili pamwamba pawo. Enzyme iyi imafikira yotsalira mafuta kuchokera ku phosphatidylcholine (lecithin) kupita ku cholesterol. Zotsatira zake, molekyulu ya hydrophobic ya cholesterol ester imapangidwa, yomwe imayenda mkati mwa HDL. Chifukwa chake, osamwa mowa HDL, wolemeretsedwa ndi cholesterol, amasintha kukhala HDL 3 - tinthu tokhwima komanso zokulirapo. HDL 3 kusinthana kwa cholesterol esters a TAG omwe ali mu VLDL ndi STD ndi kutenga mapuloteni enaake omwe amasamutsa cholesterol esters pakati pa lipoproteins. Pankhaniyi, HDL 3 khalani HDL2, kukula kwake komwe kumakulira chifukwa cha kuchuluka kwa TAG. VLDL ndi STDL mothandizidwa ndi LP-lipase amasinthidwa kukhala LDL, yomwe imapereka cholesterol kwambiri m'chiwindi. Gawo laling'ono la cholesterol limaperekedwa ku chiwindi cha HDL2 ndi HDL.

Kaphatikizidwe wa bile acid. Mu chiwindi, 500-700 mg wa bile acid patsiku amapangidwa kuchokera ku cholesterol. Kapangidwe kake kamaphatikizidwa ndi kuyambitsa kwa hydroxyl magulu omwe akutenga ma hydroxylases komanso zomwe gawo la oxidation la mbali ya cholesterol (mkuyu. 22.2):

Mkuyu. 22.2. Chiwembu cha mapangidwe bile zidulo.

Kachitidwe koyambirira kapangidwe - kapangidwe ka 7-a-hydroxycholesterol - kovomerezeka. Zochita za enzyme zomwe zimathandizira izi zimalephereka ndimapeto a njira, bile zidulo. Njira ina yotsogola ndi phosphorylation / dephosphorylation ya enzyme (mawonekedwe a phosphorylated a 7-a-hydroxylase akugwira). Kuwongolera ndikothekanso posintha kuchuluka kwa enzyme: cholesterol imayambitsa mtundu wa 7-a-hydroxylase gene, ndi kuponderezana kwa asidi acid. Madzi a chithokomiro amatengera kapangidwe ka 7-a-hydroxylase, ndi kuponderezana kwa estrogen. Kusintha koteroko kwa estrogen pa kapangidwe ka bile acid kumafotokozera chifukwa chake nthenda ya ndulu imapezeka mwa akazi nthawi 3-4 kuposa amuna.

Ma acric ndi ma chodeodeylolic acid omwe amapangidwa kuchokera ku cholesterol amatchedwa "ma bile bile". Kuchuluka kwa ma asidi amenewa kumalumikizidwa - kuwonjezera kwa glycine kapena mamolekyulu a taurine ku gulu la carboxyl la bile acid. Conjugation imayamba ndikupanga mawonekedwe a bile acids - zotumphukira za CoA, ndiye kuti taurine kapena glycine amalumikizidwa, ndipo chifukwa chake mitundu 4 ya conjugates imapangidwa: taurocholic ndi taurohenodeoxycholic, glycocholic ndi glycohenodeoxycholic acid. Amalimbikitsidwa kwambiri kuposa ma bile acids. Conjugates ndi glycine amapangidwanso katatu kuposa taurine, popeza kuchuluka kwa taurine m'thupi kumakhala kochepa. M'matumbo, ochepa a conjugates a bile bile achilengedwe amathandizidwa ndi michere ya bakiteriya yomwe imasinthidwa kukhala yachiwiri bile acids. Deoxycholic acid, wopangidwa kuchokera ku cholic, ndi lithocholic, wopangidwa kuchokera ku deoxycholic, samasungunuka komanso samachedwa kulowa m'matumbo.

Pafupifupi 95% ya ma asidi a bile omwe amalowa m'matumbo amabwerera ku chiwindi kudzera mu mitsempha ya portal, ndiye kuti amatumizidwanso mu ndulu ndikugwiritsidwanso ntchito mu emulsification yamafuta. Njira iyi ya bile acid imatchedwa kufalikira kwa magazi. Ndi ndowe, yachiwiri bile acid amachotsedwa kwambiri.

Matenda a Gallstone (cholelithiasis) ndi njira ya m'magazi momwe miyala imapangidwira mu ndulu, yomwe maziko ake ndi cholesterol.

Kutulutsidwa kwa cholesterol mu bile kuyenera kumayendera limodzi ndi kutulutsidwa kwapawiri kwa ma acid acid ndi phospholipids omwe amasunga mamolekyule a hydrophobic cholesterol mu boma la micellar. Zomwe zimayambitsa kusintha kwa chiŵerengero cha bile acid ndi cholesterol mu bile ndi izi: chakudya cholemera mu cholesterol, zakudya zopatsa mphamvu zambiri, kutsika kwa bile mu ndulu, kusokonezeka kwa kutsekeka kwa magazi, kuchepa kwa kapangidwe ka bile acid, matenda a ndulu.

Odwala ambiri omwe ali ndi cholelithiasis, kaphatikizidwe ka cholesterol amawonjezereka, ndipo kaphatikizidwe ka bile acid kameneka kamatsitsidwa, komwe kumapangitsa kuchuluka kwa cholesterol ndi bile acid zomwe zimatulutsidwa mu bile. Zotsatira zake, cholesterol imayamba kukhazikika mu ndulu, ndikupanga mawonekedwe owoneka bwino omwe pang'onopang'ono amawuma. Nthawi zina amalembedwa ndi bilirubin, mapuloteni komanso mchere wamchere. Miyala imatha kukhala ndi cholesterol yokha (miyala ya cholesterol) kapena osakaniza cholesterol, bilirubin, mapuloteni ndi calcium. Miyala ya cholesterol nthawi zambiri imakhala yoyera, ndipo miyala yosakanikirana ndi ya bulauni mumitundu yosiyanasiyana.

Mu gawo loyambirira la mapangidwe a miyala, chenodeoxycholic acid ikhoza kugwiritsidwa ntchito ngati mankhwala. Kamodzi mu ndulu, imapasuka miyala ya cholesterol pang'onopang'ono, koma njirayi imatenga nthawi yambiri.

Atherosulinosis ndi njira yodziwika ndi mawonekedwe a atherogenic zolembera zamkati mwa khoma lamitsempha. Chimodzi mwazifukwa zazikulu zakukula kwa matenda oterewa ndikuphwanya malire pakati pa kudya mafuta a kolesterol kuchokera m'zakudya, kaphatikizidwe ndi katemera kuchokera m'thupi. Odwala omwe ali ndi atherosulinosis adakweza makulidwe a LDL ndi VLDL. Pali ubale wosagwirizana pakati pa ndende ya HDL komanso mwayi wokhala ndi atherosulinosis. Izi zikugwirizana ndi lingaliro la magwiridwe antchito a LDL monga onyamula cholesterol mu minofu, ndi HDL kuchokera ku minofu.

Basic metabolic "prerequisite" yopanga atherosulinosis ndi hypercholesterolemia. (cholesterol yayikulu m'magazi).

Hypercholesterolemia akufotokozera:

1. Chifukwa chofuna kudya mafuta ambiri, mafuta ndi mafuta,

2. kupangidwira kwamtundu komwe kumakhala ndi zolakwika zobadwa mwanjira ya LDL kapena receptors ya apoB-100, komanso kuwonjezeranso kaphatikizidwe kapena katulutsidwe ka apoB-100 (munkhani ya hyperlipidemia ya banja, momwe zimayang'anira magazi ndi cholesterol ndi TAG zimakwezedwa).

Udindo wofunikira pakuwongolera kwa atherosulinosis umaseweredwa ndikusintha kwa mankhwalawa. Zosintha mwanjira yachilengedwe ya lipids ndi mapuloteni mu LDL zimapangitsa kuti zikhale zachilendo kwa thupi motero zimapezeka mosavuta kuti zigwiritsidwe ndi phagocytes.

Kusintha kwa mankhwala osokoneza bongo kumatha kuchitika m'njira zingapo:

1. glycosylation wa mapuloteni omwe amapezeka pamene kuchuluka kwa shuga m'magazi kumawonjezeka,

2. kusinthidwa kwa peroxide, zomwe zimapangitsa kusintha kwa lipids mu lipoproteins ndi kapangidwe ka apoB-100,

3. mapangidwe a autoimmune ma protein a LP-antibody (mankhwala osinthidwa amatha kuyambitsa mapangidwe a autoantibodies).

LDL Yosinthidwa imatengedwa ndi macrophages. Izi siziwongoleredwa ndi kuchuluka kwa cholesterol yomwe imamwa, monga momwe zimalowera m'maselo kudzera pama cell enieni, chifukwa chake macrophages amadzaza ndi cholesterol ndikusandulika "cell foamy" omwe amalowera mu gawo la subendothelial. Izi zimapangitsa kuti pakhale mawanga a lipid kapena mapanga khoma la mitsempha yamagazi. Pakadali pano, mtima endothelium ukhoza kukhazikika. Ndi kuwonjezeka kwa maselo a chithovu, zowonongeka za endothelial zimachitika. Zowonongeka zimathandizira kutsegula kwa ma cell. Zotsatira zake, zimasokoneza thromboxane, yomwe imalimbikitsa kuphatikizana kwa maselo, ndikuyambanso kupanga mapuloteni othandizira, omwe amathandizira kukula kwa maselo osalala. Zotsalazo zimasunthira kuchoka pamtundu wamtundu kupita mkati mwa khoma lamkati, potero zimathandizira kukula kwa chidikacho. Kuphatikiza apo, zolembera zimamera ndi minyewa yotupa, maselo omwe ali pansi pa membrane wa fibrous ndi necrotic, ndipo cholesterol imayikidwa mu malo a interellular. M'magawo omaliza a chitukuko, chinsaluchi chimaphatikizidwa ndi mchere wa calcium ndipo chimakhala chowonda kwambiri. M'dera lachiwonetserochi, ziwunda za magazi nthawi zambiri zimakhazikika, kutsekeka kwa lumen kwa chotengera, komwe kumayambitsa kusokonezeka kwakazungulira mu tsamba lolingana ndi minofu ndikukula kwa vuto la mtima.

Kuwongolera kaphatikizidwe ka cholesterol - kiyi yake ya enzyme (HMG-CoA reductase) imachitika m'njira zosiyanasiyana.

Phosphorylation / dephosphorylation wa kuchepetsa kwa HMG. Ndi kuwonjezeka kwa kuchuluka kwa insulin / glucagon, phosphorylates ya enzymeyi ndikudutsa m'dziko lokangalika. Kuchita kwa insulin kumachitika kudzera mwa michere iwiri.

HMG-CoA reductase kinase phosphatase, yomwe imatembenuza kinase kukhala mkhalidwe wopanda ntchito wa dephosphorylated:

Phosphotase HMG-CoA reductase poisintha kukhala dziko lokhazikika. Zotsatira zakuchitikazo ndikupanga kwa dephosphorylated yogwira mawonekedwe a HMG-CoA reductase.

Zotsatira zake, nthawi ya mayamwidwe, cholesterol imachuluka. Munthawi imeneyi, kupezeka kwa gawo loyambirira la kuphatikizika kwa cholesterol - acetyl - CoA imakulanso (chifukwa chodya zakudya zokhala ndi mafuta ndi mafuta, popeza CoA acetyl imapangidwa nthawi ya kuwonongeka kwa glucose ndi mafuta acids).

Mdziko la postabsorbent, glucagon kudzera mu proteiningenase A imapangitsa phosphorylation ya HMG - CoA - reductase, ndikusintha kukhala malo osagwira ntchito. Kuchita izi kumawonjezereka chifukwa chakuti nthawi yomweyo glucagon imalimbikitsa phosphorylation ndi inactivation ya phosphotase ya HMG-CoA reductase, potero kusunga HMG-CoA reductase munthawi ya phosphorylated. Zotsatira zake, kuphatikiza kwa cholesterol mu nthawi ya postabsorption komanso pakusala kudya kumalepheretsedwa ndi kuphatikizika kwa endo native. Ngati cholesterol yomwe ili mu chakudya ibweretsedwa 2%, ndiye kuti kuphatikiza kwa cholesterol amkati kumachepa kwambiri. Koma kufafaniza kwathunthu kwa cholesterol kaphatikizidwe sikuchitika.

Mlingo wa zoletsa za cholesterol biosynthesis mothandizidwa ndi cholesterol kuchokera ku chakudya chimasiyanasiyana munthu ndi munthu. Izi zikuwonetsa umodzi wa njira zamapangidwe a cholesterol. Pochepetsa kukula kwa cholesterol synthesis, ndizotheka kuchepetsa kuchuluka kwake m'magazi.

Ngati ndalama pakati pa kudya kwa cholesterol ndi chakudya ndi kapangidwe kake m'thupi mbali inayo ndi kuphwanya kwa mafuta am'mimba ndi cholesterol mbali ina ndikusweka, kuchuluka kwa mafuta m'thupi kumapangitsa kuti magazi asinthe. Zotsatira zoyipa kwambiri zimagwirizanitsidwa ndi kuwonjezeka kwa magazi cholesterol concentration (hypercholesterolemia), pomwe mwayi wokhala ndi atherosulinosis ndi cholelithiasis ukuwonjezeka.

Familial hypercholesterolemia (HCS) - mawonekedwe awa ndiwofala kwambiri - pafupifupi wodwala m'modzi pa anthu 200. Choipa chobadwa nacho ku HCS ndikuphwanya mayamwidwe a LDL ndi maselo, chifukwa chake, kutsika kwa chiwopsezo cha LDL catabolism. Zotsatira zake, kuchuluka kwa LDL m'magazi kumakwera, komanso cholesterol popeza ilipo yambiri mu LDL. Chifukwa chake, ndi HCS, kuyika kwa cholesterol mu minofu, makamaka pakhungu (xanthomas), m'makoma amitsempha yamakhalidwe pamakhala mawonekedwe.

Kuletsa kapangidwe ka HMG-CoA reductase

Choyimira chomaliza cha njira ya cholesterol metabolic. Amachepetsa kuchuluka kwa mtundu wa HMG-CoA reductase, motero kuletsa kapangidwe kake. Chiwindi chikugwirira ntchito ma asidi a bile ku cholesterol, motero ma asidi a bile amalepheretsa zochita za genge ya HMG-CoA. Popeza HMG-CoA reductase ilipo pambuyo pakupanga pafupifupi 3, zoletsa za kapangidwe ka cholesterol iyi ndizothandiza.