the small intestine and mucosal digestion
DESCRIPTION
The Small Intestine and Mucosal Digestion Eric Sibley, MD, PhD Department of Pediatrics September 25, 2015TRANSCRIPT
THE SMALL INTESTINEAND MUCOSAL
DIGESTIONEric Sibley, MD, PhD
Department of Pediatrics
September 25, 2015
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
AmylaseAmylases
Maltase
Chymotrypsin,Carboxypeptidase
Pepsin, trypsin
Monosaccharides(glucose, galactose, fructose)
ProteasesAminopeptidase
Amino AcidsPeptide FragmentsProtein
Lipase Lipases
Fats
Protein
Carbohydrate
Monoglyceride
Free FattyAcids
Nutrient MucosalDigestion
Mucosal Absorption
Triglyceride
DisacccharidePolysacccharide
LuminalDigestion
Tri/Di-peptides
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
Digestive Anatomy
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
Carbohydrate Digestion
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
AmylaseAmylases
Maltase
Monosaccharides(glucose, galactose, fructose)
Carbohydrate
Nutrient MucosalDigestion
Mucosal Absorption
DisacccharidePolysacccharide
LuminalDigestion
DIGESTION OF CARBOHYDRATE
LUMINAL MUCOSALFOOD SOURCE % OF CHO HYDROLYSIS HYDROLYSIS
STARCH 60(AMYLOPECTIN
AMYLOSE)
LACTOSE 10
SUCROSE 30
Glux
Glux
Amylose
Amylopectin
Maltotriose Maltose
-Limit Dextrins
(1-6) linkage
(1-4) linkages
DIGESTION OF CARBOHYDRATE
LUMINAL MUCOSALFOOD SOURCE % OF CHO HYDROLYSIS HYDROLYSIS
STARCH 60 MALTOSE,(AMYLOPECTIN MALTOTRIOSE,
AMYLOSE) -DEXTRINS
DIGESTION OF CARBOHYDRATE
LUMINAL MUCOSALFOOD SOURCE % OF CHO HYDROLYSIS HYDROLYSIS
STARCH 60 MALTOSE,(AMYLOPECTIN MALTOTRIOSE,
AMYLOSE) -DEXTRINS
LACTOSE 10 NONE
SUCROSE 30 NONE
DIGESTION OF CARBOHYDRATE
LUMINAL MUCOSALFOOD SOURCE % OF CHO HYDROLYSIS HYDROLYSIS
STARCH 60 MALTOSE, GLUCOSE(AMYLOPECTIN MALTOTRIOSE,
AMYLOSE) -DEXTRINS
LACTOSE 10 NONE GLUCOSE + GALACTOSE
SUCROSE 30 NONE GLUCOSE + FRUCTOSE
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
SGLT1 GLUT5
Na+ Glucose Galactose
Fructose
Glucose
Galactose
Fructose
Na+
K+Na+
K+
GLUT2ATPase
Intestinalcell
Blood
Lumen
Starch
Amylase
Maltotriose
Maltose
-Limit DextrinsSucrose Lactose
LactaseSucrase–Isomaltase Maltase-GA
Oligosaccharides
GLUT5 SGLT1
GlucoseFructose Galactose
Facilitated Diffusion Active transport
Inte
stin
al L
umen
Brus
h Bo
rder
Na+
Maturational Decline in Lactase Activity
0
20
40
60
80
100
120
140
160
180
Birth 5 10 15 20 25 30
AGE (days)
Enzyme Activity
(units/gm protein) Lactase
Sucrase
From: Henning SJ, Am. J. Physiol. 235:E451-456, 1978
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 99Fulani 58
North American (Black) 70-75 North American (White) 5-20 Thai 97
LactoseBacterial action
Lactic acid + H + CO2 osmotic effect
H2O
Distension ofGut Walls
Watery Diarrhea
Lactase
Fluid Load
IncreasedPeristalsis
Malabsorption
glucose+ galactose
Maturational Decline in Lactase Activity
0
20
40
60
80
100
120
140
160
180
Birth 5 10 15 20 25 30
AGE (days)
Enzyme Activity
(units
/gm pr
otein) Lactase
Sucrase
From: Henning SJ, Am. J. Physiol. 235:E451-456, 1978
Exon 1TATA
Regulatory Protein RNA Polymerase II Complex
Exon 1TATA
Transcription Regulation
Cis Element
Cis Element
EXON 1
5’ Lactase Gene
EXON 2PROMOTER
Lactase Promoter - Luciferase Reporter
Luciferase Gene
EXON 1
5’ Lactase Gene
EXON 2PROMOTER
Age: 7 days (six pups) Age: 4 weeks
In Vivo Detection of Luciferase Activity
gLac2K- F1 Generation: PCR + or –
+– –– –+
–+ +
esophagus
stomach
small intestine
cecum
colon
2Kb Lactase Promoter Directs Spatial Restriction of Expression
Luciferase Activity - gLac2K Transgene (jejunum)
RT-PCR mRNA Abundance
2Kb Promoter Directs Maturational Decline
1 wk 2 wk 4 wkG3PDH
Lactase
Luciferase
1 week 2 week 4 week0
500
1000
1500
2000
2500
AGE
Luc
ifera
se A
ctiv
ity(R
LU
/ug
prot
ein)
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 99Fulani 58
North American (Black) 70-75 North American (White) 5-20 Thai 97
LACTASE; LCT
Alternative titles; symbols LACLACTASE-PHLORIZIN HYDROLASE; LPH
CHROMOSOME: 2
Gene map locus 2q21
2q14.1
2q22.1
Chromosome 2
Identification of a variant associated with adult-type hypolactasiaNabil Sabri Enattah et al.
Nature Genetics 30, 233 – 237 (2002)
Identification of a variant associated with adult-type hypolactasia
EXON 1
5’ Lactase Gene
PROMOTEREXON 12
3’ MCM6 Gene
-13,910
C/T
-2,000
LACTASE PERSISTENT
C
LACTASE NON-PERSISTENT
-13910 bp SNP
CGA
T CGA
EXON 1
5’ Lactase Gene
PROMOTEREXON 12
3’ MCM6 Gene
-13,910
C/T
-2,000
Maturational Decline in Lactase Activity
0
20
40
60
80
100
120
140
160
180
Birth 5 10 15 20 25 30
AGE (days)
Enzyme Activity
(units
/gm pr
otein) Lactase
Sucrase
From: Henning SJ, Am. J. Physiol. 235:E451-456, 1978
Protein Digestion
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
AmylaseAmylases
Maltase
Chymotrypsin,Carboxypeptidase
Pepsin, trypsin
Monosaccharides(glucose, galactose, fructose)
ProteasesAminopeptidase
Amino AcidsPeptide FragmentsProtein
Protein
Carbohydrate
Nutrient MucosalDigestion
Mucosal Absorption
DisacccharidePolysacccharide
LuminalDigestion
Tri/Di-peptides
70%
30%
PepT1
PepsinChymotrypsin
Trypsin
PepT1
PepsinChymotrypsin
Trypsin
Adibi, Gastro. 113:332 (1997)
http://www.biochemtech.uni-halle.de/nbiochemie/Pept1.gif
PepT1
PepsinChymotrypsin
Trypsin
Intestinal Amino Acid Transport DisordersDisorder Substrate Cinical Features
Cystinuria Cystine, ornithine,arginine, lysine
Urinary tract calculi, hereditary pancreatitis,cerebral dysfunction, dibasic aminoaciduria. Twotypes of cystinuria exists for which the geneticmutation in Type I has been isolated to theSLC3A1 amino acid transporter gene (1995),whose protein product is involved in cystine,dibasic and neutral amino acid transport
Hartnup disease Neutral amino acids Autosomal recessive. Pellagra-like rash,cerebellar ataxia, psychiatric disorders, neutralaminoaciduria. Consistent with defect in Type Btransporter system
Blue diaper disease Tryptophan Indigo blue discolouration of diapers, notryptophanuria, growth retardation,hypercalcemia
Oasthouse urine disease Methionine Seizures, mental retardation, diarrhea, peculiarurinary odor-increased alpha hydroxybutryic acid.Methionine malabsorption.
Hyperdibasic aminoaciduria Lysine, arginine Familial protein intolerance, diarrhea, failure tothrive, hepatosplenomegaly, dibasicaminoaciduria
PepT1
PepsinChymotrypsin
Trypsin