Section4CholesterolMetabolism§4.1Structureandfunctionofcholesterol1.Functionofcholesterol:(1)Itisaconstituentofallcellmembranes.(2)Itisnecessaryforthesynthesisofallsteroidhormones,bilesaltsandvitaminD.結(jié)構(gòu)：以環(huán)戊烷多氫菲cyclopentanopenhydrophenanthrenering為母體結(jié)構(gòu)衍生而來(lái)羥基被取代形成膽固醇酯Cholesterolester膽固醇的合成位置：除成年動(dòng)物腦組織和成熟紅細(xì)胞外，幾乎全身各組織均可合成膽固醇，肝是合成膽固醇的主要場(chǎng)所，（百分之八十）膽固醇合成酶存在于胞液及內(nèi)質(zhì)網(wǎng)上，因此膽固醇的合成主要在細(xì)胞胞液及內(nèi)質(zhì)網(wǎng)中進(jìn)行合成原料：乙酰CoA（合成膽固醇的唯一碳來(lái)源）NADPHATP合成基本過(guò)程：1.甲羥戊酸mevalonate的合成HMGCoAreductase（HMGCoA還原酶）istherate-limitingenzyme，這部反應(yīng)也是合成膽固醇的限速反應(yīng).反應(yīng)過(guò)程見中文書146頁(yè)2.鯊烯squalene的合成縮合，縮合，再縮合3.膽固醇的合成只需記第一步反應(yīng)里的三步反應(yīng)和發(fā)生位置1）膽固醇的轉(zhuǎn)化和排泄SteroidhormonesBileacidsCholesterolVitaminD膽固醇可以轉(zhuǎn)變?yōu)槟懼幔惞檀技に?，維生素D2）膽汁酸：初級(jí)膽汁酸在肝中合成，限速酶是7阿爾發(fā)羥化酶。二級(jí)膽汁酸是初級(jí)膽汁酸在小腸中收到腸道細(xì)菌刺激的產(chǎn)物。。3）EnterohepaticCycleofbileacids膽汁酸的肝腸循環(huán)Conversiontobilesalts,thataresecretedintotheintestine,istheonlymechanismbywhichcholesterolisexcreted.Mostbileacidsarereabsorbedintheileum

,returnedtotheliverbytheportalvein,andre-secretedintotheintestine.Thisistheenterohepaticcycle.(4)Functionofbileacids

Bileacidsareamphipathic兩親性,withdetergent清潔劑properties.Emulsify乳化fatandaiddigestionoffats&fat-solublevitaminsintheintestine.Increasesolubilityofcholesterolinbile.轉(zhuǎn)化為固醇類激素組織：腎上腺皮質(zhì)，生殖腺。固醇類激素：Steroidhormones:cortisol皮質(zhì)醇(glucocorticoid糖皮質(zhì)激素),corticosterone皮質(zhì)酮andaldosterone醛固酮(mineralocorticoid鹽皮質(zhì)激素),progesterone黃體酮,testosterone睪酮,andestradiol雌二醇轉(zhuǎn)化為7-脫氫膽固醇（維生素D前體）

CholesterolandheartdiseaseHeartdiseaseisthe#1killerintheUSAExcesscholesterol(LDL)inthebloodresultsinatherosclerosis,(cloggingofbloodvessels)Inheritablehypercholesterolemiacausessevereatherosclerosisinchildhood(LDLishigh,HDLislow)Therapy:HMG-CoA

reductaseistheregulatoryenzymeinthecholes