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The Small Intestine and Mucosal Digestion

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Presentation on theme: "The Small Intestine and Mucosal Digestion"— Presentation transcript:

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2 The Small Intestine and Mucosal Digestion
Eric Sibley, MD, PhD Department of Pediatrics September 25, 2015

3 Learning Objectives To understand the physiological processes involved in intestinal digestion of nutrients To comprehend the mechanisms that allow for mucosal absorption of the products of intestinal nutrient digestion

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8 (glucose, galactose, fructose)
Nutrient Luminal Digestion Mucosal Digestion Mucosal Absorption Carbohydrate Polysacccharide Disacccharide Monosaccharides (glucose, galactose, fructose) Amylases Amylase Maltase Protein Protein Peptide Fragments Amino Acids Proteases Chymotrypsin, Carboxypeptidase Pepsin, trypsin Aminopeptidase Tri/Di-peptides Fats Triglyceride Monoglyceride Lipase Lipases Free Fatty Acids

9 The Small Intestine - Nutrient Digestion
I. Anatomy II. Carbohydrate Digestion A. Luminal and Mucosal digestion of starch/glycogen B. Mucosal digestion of oligosaccharides – Lactase – Carbohydrate malabsorption C. Mucosal transport of monosaccharides – SGLT1, GLUT5 III. Protein Digestion A. Luminal and Mucosal digestion of proteins B. Mucosal transport of peptides and AA C. Intracellular digestion of peptides

10 Digestive Anatomy

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27 Normal small intestinal mucosa is seen at the left, and mucosa involved by celiac sprue at the right. There is blunting and flattening of villi with celiac disease, and in severe cases a loss of villi with flattening of the mucosa as seen here. Normal Celiac Sprue

28 Carbohydrate Digestion

29 The Small Intestine - Nutrient Digestion
I. Anatomy II. Carbohydrate Digestion A. Luminal and Mucosal digestion of starch/glycogen B. Mucosal digestion of oligosaccharides – Lactase – Carbohydrate malabsorption C. Mucosal transport of monosaccharides – SGLT1, GLUT5 III. Protein Digestion A. Luminal and Mucosal digestion of proteins B. Mucosal transport of peptides and AA C. Intracellular digestion of peptides

30 (glucose, galactose, fructose)
Nutrient Luminal Digestion Mucosal Digestion Mucosal Absorption Carbohydrate Polysacccharide Disacccharide Monosaccharides (glucose, galactose, fructose) Amylases Amylase Maltase

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32 DIGESTION OF CARBOHYDRATE
LUMINAL MUCOSAL FOOD SOURCE % OF CHO HYDROLYSIS HYDROLYSIS STARCH 60 (AMYLOPECTIN AMYLOSE) LACTOSE 10 SUCROSE 30

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35 Amylose Glux Maltotriose Maltose -Limit Dextrins Glux Amylopectin
(1-4) linkages Maltotriose (1-6) linkage Maltose -Limit Dextrins Glux Amylopectin

36 DIGESTION OF CARBOHYDRATE
LUMINAL MUCOSAL FOOD SOURCE % OF CHO HYDROLYSIS HYDROLYSIS STARCH 60 MALTOSE, MALTOTRIOSE, (AMYLOPECTIN -DEXTRINS AMYLOSE)

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38 DIGESTION OF CARBOHYDRATE
LUMINAL MUCOSAL FOOD SOURCE % OF CHO HYDROLYSIS HYDROLYSIS STARCH 60 MALTOSE, MALTOTRIOSE, (AMYLOPECTIN -DEXTRINS AMYLOSE) LACTOSE 10 NONE SUCROSE 30 NONE

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40 DIGESTION OF CARBOHYDRATE
LUMINAL MUCOSAL FOOD SOURCE % OF CHO HYDROLYSIS HYDROLYSIS STARCH 60 MALTOSE, GLUCOSE MALTOTRIOSE, (AMYLOPECTIN -DEXTRINS AMYLOSE) LACTOSE 10 NONE GLUCOSE + GALACTOSE SUCROSE 30 NONE GLUCOSE + FRUCTOSE

41 The Small Intestine - Nutrient Digestion
I. Anatomy II. Carbohydrate Digestion A. Luminal and Mucosal digestion of starch/glycogen B. Mucosal digestion of oligosaccharides – Lactase – Carbohydrate malabsorption C. Mucosal transport of monosaccharides – SGLT1, GLUT5 III. Protein Digestion A. Luminal and Mucosal digestion of proteins B. Mucosal transport of peptides and AA C. Intracellular digestion of peptides

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45 Starch Amylase Sucrose -Limit Dextrins Oligosaccharides Lactose
Intestinal Lumen Maltotriose Maltose Fructose Glucose Galactose Na+ Brush Border GLUT5 Sucrase–Isomaltase Maltase-GA SGLT1 Lactase Facilitated Diffusion Active transport

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50 Maturational Decline in Lactase Activity
Enzyme Activity (units/gm protein) Sucrase AGE (days) From: Henning SJ, Am. J. Physiol. 235:E , 1978

51 Prevalence Of Lactase Deficiency In Healthy Populations
Group Lactase Deficient (%) African Bantu 50 Chinese 87 Danish 3 Eskimo (Greenland) 88 Filipino 95 Indian 55 Mexican 74 Nigerian Yoruba 99 Fulani 58 North American (Black) North American (White) 5-20 Thai

52 Lactose Lactase Bacterial action glucose+ galactose
Lactic acid + H + CO2 osmotic effect H2O Fluid Load Distension of Gut Walls Increased Peristalsis Watery Diarrhea Malabsorption

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55 Maturational Decline in Lactase Activity
Enzyme Activity (units/gm protein) Sucrase AGE (days) From: Henning SJ, Am. J. Physiol. 235:E , 1978

56 Transcription Regulation
Cis Element TATA Exon 1 Regulatory Protein RNA Polymerase II Complex Cis Element TATA Exon 1

57 5’ Lactase Gene EXON 1 EXON 2 PROMOTER

58 Lactase Promoter - Luciferase Reporter
Luciferase Gene PROMOTER EXON 1 EXON 2 5’ Lactase Gene

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60 In Vivo Detection of Luciferase Activity
gLac2K- F1 Generation: PCR + or – Age: 7 days (six pups) Age: 4 weeks – + – – + – + – +

61 2Kb Lactase Promoter Directs Spatial Restriction of Expression
esophagus stomach small intestine cecum colon

62 2Kb Promoter Directs Maturational Decline
Luciferase Activity - gLac2K Transgene (jejunum) RT-PCR mRNA Abundance 1 wk wk wk G3PDH Lactase Luciferase

63 Prevalence Of Lactase Deficiency In Healthy Populations
Group Lactase Deficient (%) African Bantu 50 Chinese 87 Danish 3 Eskimo (Greenland) 88 Filipino 95 Indian 55 Mexican 74 Nigerian Yoruba 99 Fulani 58 North American (Black) North American (White) 5-20 Thai

64 2q14.1 Chromosome 2 2q22.1 LACTASE; LCT Alternative titles; symbols
LACTASE-PHLORIZIN HYDROLASE; LPH CHROMOSOME: 2 Gene map locus 2q21 Chromosome 2 2q22.1

65 Identification of a variant associated with adult-type hypolactasia
Nabil Sabri Enattah et al. Nature Genetics 30, 233 – 237 (2002)

66 Identification of a variant associated with adult-type hypolactasia

67 3’ MCM6 Gene 5’ Lactase Gene C/T PROMOTER EXON 12 EXON 1 -13,910
-2,000

68 LACTASE NON-PERSISTENT
G C C bp SNP A G T C LACTASE PERSISTENT

69 3’ MCM6 Gene 5’ Lactase Gene C/T PROMOTER EXON 12 EXON 1 -13,910
-2,000

70 Maturational Decline in Lactase Activity
Enzyme Activity (units/gm protein) Sucrase AGE (days) From: Henning SJ, Am. J. Physiol. 235:E , 1978

71 Protein Digestion

72 The Small Intestine - Nutrient Digestion
I. Anatomy II. Carbohydrate Digestion A. Luminal and Mucosal digestion of starch/glycogen B. Mucosal digestion of oligosaccharides – Lactase – Carbohydrate malabsorption C. Mucosal transport of monosaccharides – SGLT1, GLUT5 III. Protein Digestion A. Luminal and Mucosal digestion of proteins B. Mucosal transport of peptides and AA C. Intracellular digestion of peptides

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74 (glucose, galactose, fructose)
Nutrient Luminal Digestion Mucosal Digestion Mucosal Absorption Carbohydrate Polysacccharide Disacccharide Monosaccharides (glucose, galactose, fructose) Amylases Amylase Maltase Protein Protein Peptide Fragments Amino Acids Proteases Chymotrypsin, Carboxypeptidase Pepsin, trypsin Aminopeptidase Tri/Di-peptides

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77 PepT1 Pepsin Chymotrypsin Trypsin

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79 Pepsin Chymotrypsin Trypsin PepT1

80 Adibi, Gastro. 113:332 (1997)

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82 Pepsin Chymotrypsin Trypsin PepT1

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85 Pepsin Chymotrypsin Trypsin PepT1

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