肝胆胰的生物化学 Hepatobiliary and pancreatic biochemical

1. 肝胆胰的生物化学Hepatobiliary and pancreatic biochemical

2. The digestive system consists of • alimentary tract: • mouth, pharynx, esophagus, stomach,small intestines, • large intestines, rectum , anus • accessory ograns • Salivary glands, liver, gall bladder, pancreas

3. Liver 肝 is the largest gland in the body.The Liver is divided into two major lobes and two smaller lobes on the surgace. • Functions: • Secretion • Synthesis of bile • Synthesis of plasma protein storage • Detoxification • Excretion • Carbohydrate metabolism • Protein metabolism • filtering

4. 双重供血系统 • 70-75%来自门静脉（ hepatic portal vein ） • 25-30%来自肝动脉（ hepatic artery ） 双重输出通道 • 肝静脉(（ hepatic vein ） • 胆道(bile tract)

5. Gall bladder 胆囊 • Major functions: • Bile storage • Bile concentration, modification

7. 从肝脏初分泌的胆汁，透明澄清，固体物含量 较少。呈桔黄色或金黄色。 肝 胆 汁 Hepatic bile 胆汁（bile） 肝胆汁进入胆囊后，胆囊壁吸收肝胆汁中的水、盐及其它一些成分，并分泌粘液渗入胆汁，使胆汁浓缩，成为胆囊胆汁，呈暗褐色或棕绿色。 胆囊胆汁 Gallbladder bile 正常人每 天平均分泌胆汁300~700ml

8. 胆汁的组成 Composition of Bile •  water (~85%)  • bile salts (~10%) • mucus and pigments (~3%) • fats (~1%) • inorganic salts (~0.7%) • cholesterol (~0.3%)

9. 两种胆汁的百分组成

10. Bile acids • Bile acids are the end products of cholesterol metabolism • Bile acids are steroid acids found predominantly in the bile of mammals. • Bile salts: are bile acids compounded with a cation, usually sodium

11. Type of bile acid free bile acid (游离胆汁酸) • cholic acid 胆酸 • deoxycholic acid 脱氧胆酸 • chenodeoxycholic acid 鹅脱氧胆酸 • lithocholic acid石胆酸 conjugated bile acid (结合胆汁酸) Conjugated bile acids are more efficient at emulsifying fats because, at intestinal pH, they are more ionized than unconjugated bile acids.

12. Free bile acid deoxycholic acid(脱氧胆酸) cholic acid(胆酸) lithocholic acid(石胆酸) chenodeoxycholic acid(鹅脱氧胆酸)

13. Conjugated bile acid CONHCH2COOH CONHCH2CH2SO3H taurocholic acid(牛磺胆酸) glycocholic acid (甘氨胆酸)

14. primary bile acids（初级胆汁酸）: are synthesized in the liver and conjugated with taurine or glycine before secretion via bile into the intestine. cholic acid 胆酸 chenodeoxycholic acid 鹅脱氧胆酸 secondary bile acids（次级胆汁酸） : are derived from the primary bile acids by the enzymatic action of intestinal bacteria through the process of deconjugation and dehydroxylation. deoxycholic acid 脱氧胆酸 lithocholic acid 石胆酸

15. secondary bile acid primary bile acid 7alpha-dehydroxylatio 7alpha-dehydroxylatio deoxycholic acid cholic acid chenodeoxycholic acid lithocholic acid

16. Function of bile acids • eliminating cholesterol from the body • driving the flow of bile to eliminate catabolites from the liver • emulsifying lipids and aids the processof  digestion of  lipids in the small intestine • facilitate the intestinal absorption of fat-soluble vitamins.

17. Hydrophobic side Hydrophilic side glycocholic acid

18. 胆汁酸的生成 （一）初级胆汁酸的生成 • 部位：肝细胞胞液和微粒体 • 原料：胆固醇 • 限速酶：胆固醇7α-羟化酶

19. 胆固醇 7α—羟胆固醇 初级游离胆汁酸（胆酸、鹅脱氧胆酸） 初级结合型胆汁酸 （甘氨胆酸、牛磺胆酸、甘氨鹅脱氧胆酸、牛磺鹅脱氧胆酸） 7α—羟化酶 加氢，羟化，侧链氧化，断链 牛磺酸 甘氨酸结合

20. 胆汁酸代谢的调节 胆固醇合成限速酶 HMG CoA还原酶被胆汁酸抑制； 高胆固醇膳食抑制此酶而激活7α-羟化酶 ① 受胆汁酸反馈调节 7α-羟化酶是限速酶 ② 受胆固醇的调节 胆固醇合成与胆汁酸合成具有协同关系 ③ 受糖皮质激素和生长激素调节 促进7-α羟化酶活性

21. 肠菌 次级胆汁酸 初级胆汁酸 水解、脱羟 （二） 次级胆汁酸的生成 • 部位：小肠下段和大肠 • 过程：

22. （三）胆汁酸的肠肝循环 胆汁酸随胆汁排入肠腔后，约95%胆汁酸可经门静脉重吸收入肝，在肝内转变为结合胆汁酸,并与肝新合成的胆汁酸一道再次排入肠道，此循环过程称胆汁酸的肠肝循环 (enterohepatic circulation of bile acid)。 • 意义：将有限的胆汁酸反复利用以满足人体对 • 胆汁酸的生理需要。

23. 机体内胆汁酸储备的总量称为胆汁酸库(bile acid pool)。 胆汁酸肠肝循环的过程

24. Pancreas 胰脏 Makes pancreatic juices and hormones

25. Function The pancreas is both an exocrineand an endocrine gland. The exocrine portion of the gland produces a secretion that contains enzymes that are capable of hydrolyzing proteins,fats,and crabohydrates. The endocrine portion of the gland, the pancreatic islet, produces the hormones insulin and glucagons that play a key role in carbohydrate metabolism

26. Pancreatic juice • Pancreatic juice is clear, colorless and watery solution. pH is 8.0-8.3 • Contains 1.5% solids • 2/3 of solids : inorganic matter • 1/3 of solids : organic matter.

27. inorganic matter • HCO3: content is very high ( 5 times more then the plasma). • Cl • Na • K • small amounts of Phosphate, Ca, Mg.

28. Organic matter: enzyme or proenzyme • Enzymes are produced, stored and released as their inactive precursors so that they don’t digest and destroy the pancreas itself. Main pancreatic enzyme : • protease • trypsin • chymotrypsin • elastase • Carboxypeptidase • pancreatic lipase • Amylase

29. Trypsin • Inactive : trypsinogen. • Activated by enteropeptidase ( 肠激酶）. • Properties : Alkaline pH 8.0-9.0 Endopeptidase Activates other pancreatic proenzyme is active against the peptide bonds in protein molecules that have carboxyl groups donated Arg and Lyr Trypsin inhibitor is present in the pancreatic juice as well as in the plasma.

30. Chymotrypsin • secreted in the inactive form. • Activated by trypsin. • Endopeptidase • pH 8-9 • is active against the peptide bonds in protein molecules that have carboxyl groups donated Tyr,Phe,Trp,Met and Leu

31. Pancreatic lipase • It is water soluble and can act only on the surface of fat globules after their emulsification. • Acts only in the presence of bile salts which seems to activate it. • Activity is increased by certain proteins and amino acids. • Optimum pH is 8.2- 9.2.

32. Zymogen Activation by Proteolytic Cleavage

33. Regulation of pancreatic juice secretion • secrtin (促胰液素） • cholecystokinin(CCK, 胆囊收缩素)