肝胆胰的生物化学Hepatobiliary and

pancreatic biochemical

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

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

70-75% 来自门静脉（ hepatic portal vein ）

25-30% 来自肝动脉（ hepatic artery ）

肝静脉 ( （ hepatic vein ）

胆道 (bile tract)

双重供血系统

双重输出通道

Gall bladder 胆囊Major functions:

Bile storage

Bile concentration, modification

胆汁（ bile ）

肝 胆 汁Hepatic bile

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。

胆囊胆汁 Gallbladder 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。

正常人每 天平均分泌胆汁 300~700ml

•  water (~85%) 

• bile salts (~10%)

• mucus and pigments (~3%)

• fats (~1%)

• inorganic salts (~0.7%)

• cholesterol (~0.3%)

胆汁的组成 Composition of Bile

两种胆汁的百分组成肝胆汁 胆囊胆汁

比重 1.009 ～ 1.013 1.026 ～ 1.032

pH 7.1 ～ 8.5 5.5 ～ 7.7

水 96 ～ 97 80 ～ 86

固体成分 3 ～ 4 14 ～ 20

无机盐 0.2 ～ 0.9 0.5 ～ 1.1

粘蛋白 0.1 ～ 0.9 1 ～ 4

胆汁酸盐 0.5 ～ 2 1.5 ～ 10

胆色素 0.05 ～ 0.17 0.2 ～ 1.5

总脂类 0.1 ～ 0.5 1.8 ～ 4.7

胆固醇 0.05 ～ 0.17 0.2 ～ 0.9

磷脂 0.05 ～ 0.08 0.2 ～ 0.5

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

Type of bile acid

free bile acid ( 游离胆汁酸 )

conjugated bile acid ( 结合胆汁酸 )

• cholic acid 胆酸•deoxycholic acid 脱氧胆酸• chenodeoxycholic acid 鹅脱氧胆酸• lithocholic acid 石胆酸

Conjugated bile acids are more efficient at emulsifying fats because, at inte

stinal pH, they are more ionized than unconjugated bile acids.

Free bile acid

cholic acid( 胆酸 )

chenodeoxycholic acid( 鹅脱氧胆酸 )

deoxycholic acid ( 脱氧胆酸 )

lithocholic acid( 石胆酸 )

Conjugated bile acid

CONHCH2CH2SO3H

HOH OH

OH

3

12

7

taurocholic acid( 牛磺胆酸 )

glycocholic acid ( 甘氨胆酸 )

CONHCH2COOH

HOH OH

OH

3

12

7

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

deoxycholic acid

lithocholic acid

secondary bile acidprimary bile acid

cholic acid

chenodeoxycholic acid

7alpha-dehydroxylatio

7alpha-dehydroxylatio

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 process of  digestion of  lipids

in the small intestine

• facilitate the intestinal absorption of fat-soluble vitamins.

13

14

98

10

17

11 1516

5

61

4

2

OH

CH3

OH

CH3

CO

HN

CH2

HOOC

CH3

OH

Hydrophobic side

Hydrophilic side

glycocholic acid

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

（一）初级胆汁酸的生成

胆汁酸的生成

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

① ① 受胆汁酸反馈调节受胆汁酸反馈调节 7α-7α- 羟化酶是限速酶 羟化酶是限速酶

② ② 受胆固醇的调节受胆固醇的调节 胆固醇合成与胆汁酸合成具有协同关系胆固醇合成与胆汁酸合成具有协同关系

③ ③ 受受糖皮质激素和生长激素调节糖皮质激素和生长激素调节 促进促进 7-α7-α 羟化酶活性羟化酶活性

胆汁酸代谢的调节胆汁酸代谢的调节

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

胆固醇合成限速酶

（二） 次级胆汁酸的生成

部位：小肠下段和大肠过程：

初级胆汁酸 次级胆汁酸肠菌水解、脱羟

（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。

胆汁酸肠肝循环的过程

机体内胆汁酸储备的总量称为胆汁酸库

(bile acid pool) 。

Makes pancreatic juices and hormones

Pancreas 胰脏

Function The pancreas is both an exocrine and 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

• 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.

Pancreatic juice

• HCO3: content is very high ( 5 times more then the plasma).

• Cl • Na • K • small amounts of Phosphate, Ca, Mg.

inorganic matter

Organic matter: enzyme or proenzymeEnzymes 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

Inactive : trypsinogen. Activated by enteropeptidase ( 肠激酶） . Properties :

Trypsin

a. Alkaline pH 8.0-9.0

b. Endopeptidase

c. Activates other pancreatic proenzyme

d. is active against the peptide bonds in protein molecules that have

carboxyl groups donated Arg and Lyr

e. Trypsin inhibitor is present in the pancreatic juice as well as in the

plasma.

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

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.

 Zymogen Activation by Proteolytic Cleavage

secrtin ( 促胰液素）

cholecystokinin (CCK, 胆囊收缩素 )

Regulation of pancreatic juice secretion