Digestion in the intestine Digestion of macromolecules into

第四节 小肠内消化(Digestion in the intestine)

• Digestion of macromolecules into absorbable units is accomplished by a combination of mechanical and enzymatic breakdown. • The PH at which different digestive enzyme function best reflects the location where they are most active.

Villi of the Human Intestine

一、胰液的分泌(Secreting the Panceatic Juice) • Pancreatic Enzymes -Carbohydrate digestion: amylase -Lipid digestion: lipase -Protein digestion: Trypsinogen; Chymotrypsinogen Procarboxypeptidase Enterokinase: enzyme in the brush border of the small bowel that activates trypsinogen by cleaving it into trypsin Trypsin activates other enzymes and is autocatalytic

Secretion of bicarbonate by duct cells Secretion of digestive enzymes by acinar cells

Pancreatic Juice Pancreatic Exocrine Function Secretory unit: Acinus-acinar cells that secrete enzymes CCK acts here to stimulate secretion Ductule-ductal cells secrete bicarbonate Secretin acts here to stimulate secretion

• Trypsin converts all other zymogens to active forms, 肠激酶激活胰蛋白酶， 胰蛋白酶可激活其它酶 Duodenum

胰导管分泌Na. HCO 3 CFTR cystic fibrosis transmembrane conductance regulator • Crypt cell in small intestine, colon secrete isotonic Na. Cl in this way and Na , water via paracellular pathway. NKCC cotransporter

Bicarbonate secretion Blood Lumen H 2 O HCO 3 - Cl. Na+ H 2 O HCO 3 CFTR H 2 CO 3 CO 2 HCO 3 - Na+ H+ - H+ ATP Cl. Na+ H 2 O

Bicarbonate function 1. Neutralize gastric acid emptied into the duodenum 2. Provide a favorable alkaline environment for optimal activity of pancreatic enzymes 1. 促胰液素是调节胰导管分泌HCO 3 -的最重要的体液因素, 其特点是水、电解质和HCO 3 -含量多，酶含量相对较少 2. CCK是是调控胰液蛋白成分释分的生理性因子, 引起大量 酶原、液体量少的胰液分泌

Cholecystokinin stomach duodenum CCK I cells Peptides Amino Vagus afferent CCK release peptide + nerve – acids, Fatty Acid H pancreas vagovagal Fat reflex 5 -HT Enzymes

Secretin H+ Fat Peptides S cells Secretin HCO 3 H 2 O

Intestinal phase of secretion VAGUS CCK Peptides Amino acids Fat, H+ Secretin HCO 3 Enzymes ACh

Control of Pancreatic Function

二、胆汁分泌和排出 Biliary secretion

In fasting state Bile stored in gall bladder& concentrated Liver HCO 3 - Aqueous secretion from duct epithelium rich in HCO 3 - and stim. by secretin HCO 3 - Cl. Na+ H 2 O Fluid & electrolytes absorbed by active transport of Na+ Sphincter of Oddi (closed)

Digestion - fat in duodenum stimulates CCK release from I cells FAT CCK Gall bladder contraction BILE Sphincter of Oddi relaxes

Liver secretion The enterohepatic circulation 胆盐的肠-肝循环 Portal vein Gallbladder. Common bile duct storage & concentration Duodenumdigestion & emulsification Ileum absorption of bile acids

Up to 95% of the cholesterol -based bile salts are “recycled” by reabsorption along the intestine. Inhibition of reabsorption results in synthesis of new bile acids and lowering of cholesterol levels. Increasing dietary fiber could trap a greater percentage of the bile in the fibrous feces.

1 -5 cm of segments alternately contract and relax(circular M. ), while longitudinal M. relax, Keeping intestinal contents in contact with the absorptive epithelum

Absorption of Nutrients Carbohydrates: Amylase oligosaccharides monosaccharides brush border enzymes maltase, sucrase, lactase, others Proteins: Pepsin, Pancreatic enzymes Amino acids, dipeptides, tripeptides Lipids: Lipase, bile acids Fatty acids and glycerol Na+cotransport: amino acids, monosaccharides into the cell and from the cell into the blood (capillaries) Lipids: fatty acids and glycerol into lacteals lymphatic system

Intestine, Absorption • Brush border contains villi which increase the surface of absorption • The villi are structured for nutrient absorption • Through small intestine walls • Absorbed into -Blood – water soluble nutrients -Lymph – fat soluble nutrients • Blood → liver → general circulation • Liver detoxifies and repackages

Summary of Enzymatic Digestion and Absorption-1 Secretion Enzyme Substrate Action Final Product Saliva Starch amylase Lingual lipase Hydrolysis to form dextrins, maltotriose, and maltose Gastric juice Pepsin Protein Hydrolysis of peptide bonds Gastric lipase Fats Hydrolysis into free fatty acids Fatty acids and glycerol

Summary of Enzymatic Digestion and Absorption 2 Secretion Enzyme Substrate Action Final Product Pancreatic exocrine secretion Trypsin Protein Cleave peptide bonds on carboxyl side Polypeptides Chymotrypsin Protein Hydrolysis Polypeptides Carboxypeptidase Ribonuclease Polypeptides Ribonucleic acids Fibrous protein Hydrolysis Amino acids Hydrolysis Mononucleotides Amino acids Elastase Hydrolysis

Summary of Enzymatic Digestion and Absorption-3 Secretion Enzyme Substrate Action Final Product Pancreatic exocrine secretion Lipase Fat Hydrolysis to Fatty monoacids glycerides Cholesterol esterase Hydrolysis to Cholesesters of terol cholesterol and fatty acids -Amylase Hydrolysis Starch, dextrins Dextrin, maltose

Enzymatic Digestion and Absorption -4 Secretion Enzyme Substrate Action Brush border enzymes Isomaltase Dextrin Hydrolysis Glucose Maltase Maltose Hydrolysis Glucose Lactase Lactose Hydrolysis Glucose, galactose Nucleotidases Nucleic acid Final Product Hydrolysis Nucleotides Nucleosidase Hydrolysis Purine and s pyrimidine phosphorylase bases

Summary of Enzymatic Digestion and Absorption-5 Secretion Enzyme Substrate Brush border Carboxy. Polypepenzymes peptidase; tides aminopeptidase; dipeptidase Action Final Product Hydrolysis Amino acids Enterokinase Trypsinogen Activates to trypsin Polypeptidases and peptides Sucrase Sucrose Hydrolysis Glucose, fructose

• - 9 liters pass through the lumen of GI tract: Equal one-sixth of total body water volume (42 L), more than twice the plasma volume(3 L) Only 2 L. enter GI via mouth Remaining 7 L secreted, half from accessory glands, remaining 3. 5 L are secreted by epithelial cells of GI tract.

Transport Pathways through the Cell Membrane， 吸收方式

The Gradual Breakdown of Large Starch Molecules 糖的吸收

Process of Digestion of Carbohydrate

Absorption of carbohydrates SGLT: Na+-glucose symporter Fructose absorption Is not Na-dependent, move across apical M. by facilitated diffu. on GLUT 5, across basolateral M. by GLUT 2

. 蛋白质的吸收 30 -60% of protein from sloughing of dead cells& enzyme A lesser role in digestion Exopeptidase

蛋白质消化的终产物 氨基酸生成于三个地方： 小肠肠腔、刷状缘 和上皮细胞内 Free amino acids, dipeptides, tripeptides are carried by Nadependent cotransporter. dipeptides, tripeptides are digested cytoplasmic peptidase, across BL M

脂类的吸收 Bile salts coat lipids to make emulsion Micelles are small disks with bile salts, phospholipids, fatty acids Cholesterol, mono- and diglycerides

Remove 2 fatty acids from each triglyceride molecule

脂类消化产物 脂肪酸、胆固 醇和甘油一酯 在刷状缘表面， 顺浓度梯度扩 散入细胞，在 滑面内质网迅 速合成甘油三 酯和胆固醇酯。 上皮细胞把合 成的甘油三酯、 胆固醇酯、磷 脂和脫辅基蛋 白组装成乳糜 微粒 ① bile salts coat fat droplets ②lipase breakdown fats into monoglycerides and fatty acids stored in micelles ③Monog. . and fatty acids move out of miscelles and enter cells by diffusion Cholesterol transported Into cell by M. transporte ④absorbed fats combine with cholesterol and protein to form chylomicrons ⑤Chylomicrons are released into lymphatic system

• TG are degraded to MG and fatty-acids. They are absorbed into the cell by diffusion. The cell resynthesizes TG. Because TG are not soluble in H 2 O, the TG are surrounded with proteins and packaged into chylomicrons • The chylomicrons are emptied into lymphatic capillaries, the lacteal lymph circulation blood cells and liver

水、电解质的吸收 Movement of ions across enterocytes in the small intestine. Cl– enters the enterocyte from the interstial fluid (IF) via the Na+–K+– 2 Cl– cotransporter on its basolateral surface and is secreted into the intestinal lumen via Cl– channels, some of which are activated by cyclic AMP. K+ recycles to the IF via basolateral K+ channels

Absorptive state

Post-absorptive state

第五节 大肠的功能 The Large Intestine No villi or enzymes present n Little digestion occurs n Absorption of water, some minerals, vitamins n Bacteria break down fiber; Bacterial action to produce gases and organic acids， produce Vitamin K，thiamin, vitamin B 12, riboflavin n Formation of feces for elimination n

小肠和大肠吸收的比较 • The Colon -Primary function is water absorption As move R L, stool becomes more formed and mucus secreting cells more numerous (lubrication) -In the rectum, almost all the cells are Goblet mucus secretors