胆固醇代谢要点

1,25-(OH)2-D3 （active Vit D3）
Cholesterol and heart disease
Heart disease is the #1 killer in the USA ♥ Excess cholesterol (LDL) in the blood results in atherosclerosis, (clogging of blood vessels) ♥ Inheritable hypercholesterolemia causes severe atherosclerosis in childhood (LDL is high, HDL is low) Therapy: ☺ HMG-CoA reductase is the regulatory enzyme in the cholesterol synthesis pathway ☺ Lovastatin (洛伐他汀) and compactin（美伐他汀） inhibit HMG-CoA reductase
转化为7-脱氢胆固醇（维生素D前体）
cholesterol （in skin） 25-hydroxylase (microsome in the liver)
ultraviolet light 7-dehydrocholecalciferol (VD3) cholesterol
25-OH-D3
1α-hydroxylase (mitochondria in the kidney)
♥
Regulation of cholesterol synthesis
fasting Glucagon
HMG CoA
HMG CoA reductase
MVA
cholesterol
after meal
insulin
源自文库
thyroxine
1.限速酶：抑制酶的活性可以抑制此反应 2.饥饿与饱食：饥饿可以抑制肝合成胆固醇，但不影响其他部位， 3.胆固醇：抑制上述酶的合成抑制胆固醇的合成
2）胆汁酸：初级胆汁酸在肝 中合成，限速酶是7阿尔发羟 化酶。二级胆汁酸是初级胆汁 酸在小肠中收到肠道细菌刺激 的产物。。
3）Enterohepatic Cycle of bile acids胆汁酸的肝肠循环
(4) Function of bile acids Bile acids are amphipathic两亲 性, with detergent 清洁剂 properties. • Emulsify 乳化fat and aid digestion of fats & fatsoluble vitamins in the intestine. • Increase solubility of cholesterol in bile.
转化为固醇类激素
组织：肾上腺皮质，生殖腺。
固醇类激素：Steroid hormones: cortisol 皮质醇 (glucocorticoid糖皮质激素), corticosterone皮质酮 and aldosterone醛固酮 (mineralocorticoid盐皮质激素), progesterone黄体酮, testosterone睾酮, and estradiol雌二醇
bile acid
4.激素：胰岛素和甲状腺素能诱导上述酶的合成，胰高血糖素抑制。另外甲状腺素还能促进胆固醇在肝外 转变为胆酸且作用较强，所以甲状腺素增多时，胆固醇反而变少
1）胆固醇的转化和排泄
Bile acids Steroid Vitamin D hormones Cholesterol
胆固醇可以转变为胆汁酸，类固 醇激素，维生素D
只需记第一步反应里的三步反应和发生位置
HMG-CoA reductase HMG CoA 还原酶

integral membrane protein 膜内在蛋白in the ER carries out an irreversible reaction 不可逆反应 It is an important regulatory enzyme in cholesterol synthesis
Section 4
Cholesterol Metabolism
§ 4.1 Structure and function of cholesterol
1. Function of cholesterol: (1) It is a constituent of all cell membranes. (2) It is necessary for the synthesis of all steroid hormones, bile salts and vitamin D.
结构：以环戊烷多氢菲 cyclopentanopenhydrophenan threne ring为母体结构衍生而来
羟基被 取代形成胆固醇 酯Cholesterol ester
胆固醇的合成 位置：除成年动物脑组织和成熟红细胞外，几乎全身各组织均可合成胆固醇，肝是合 成胆固醇的主要场所，（百分之八十） 胆固醇合成酶存在于胞液及内质网上，因此胆固醇的合成主要在细胞胞液及内质网中进行 合成原料：乙酰CoA（合成胆固醇的唯一碳来源） 合成基本过程：1.甲羟戊酸mevalonate的合成 HMG CoA reductase（ HMG CoA 还原酶） is the rate-limiting enzyme，这部反应也是合成胆固醇的限速反应. 反应过程见中文书146页 2.鲨烯squalene的合成 缩合，缩合，再缩合 3.胆固醇的合成 NADPH ATP
Conversion to bile salts, that are secreted into the intestine, is the only mechanism by which cholesterol is excreted.
Most bile acids are reabsorbed in the ileum , returned to the liver by the portal vein, and re-secreted into the intestine. This is the enterohepatic cycle.