Download Cell Bio 8- Small Intestine Phase I Function of Small Intestine

Cell Bio 8- Small Intestine Phase I
•
•
•
•
•
Function of Small Intestine
Mix intestinal content to ensure proper assimilation
Assimilation of nutrients
• Digestion
• Absorption
Regulate the emptying of chyme from the stomach
Regulate pancreatic secretions
Continue the movement of unabsorbed digested material through the alimentary tract
Functional Anatomy
• Segmentation
• Ensures proper mixing
• Maximizes exposure to digestive enzymes
• Maximizes exposure to intestinal mucosa
• Structure
• Maximize the intestinal mucosa surface area
• Circular folds X 3
• Villi X 30
• Small finger-like projections of the mucosal surface
• Microvilli X 600
• Cover each epithelial cell (enterocyte)
• Enterocytes rapidly turn over every 2-3 days
Digestion
• Chemical breakdown of foodstuff
• Three types
• Luminal
• Intraluminal enzymes
• Salivary, stomach and pancreatic enzymes
• Membrane
• Brush border enzymes
• Intracellular
• Intracellular peptidases
• Note: Intracellular digestion doesn’t occur for all nutrients. Lipid are reconstructed intracellularly
Absorption
•
•
•
Stomach
• Limited digestion and absorption
Small intestine
• Primary area for absorption of most nutrients
• Principally occurs in the duodenum and jejunum
Colon
• Very little nutrient absorption
• Absorption of water and electrolytes
Hydrolysis
 Hydro “water” lysis “separation”
• The cleavage of a chemical bond by the addition of water
• All three major nutrients undergo hydrolysis during digestion
• Proteins
• Long-chain amino acids joined together by peptide bonds between carboxyl and amino groups
• Hydrolysis breaks down proteins into shorter peptide chains and individual amino acids
Cell Bio 8- Small Intestine Phase I
•
•
•
•
•
Carbohydrates
• Oligosaccharides and polysaccharides are broken down to monosaccharides
• Only monosaccharides are absorbed by the small intestine
Lipids
• Triglycerides
• 3 free fatty acid molecules on a glycerol backbone
• Hydrolysis separates the fatty acid molecules from the glycerol
Carbohydrates
Starch
• Polymers of glucose
• Amylose--Straight-chain polymers
• Amylopectin--Branched-chain polymers
Disaccharides
• Sucrose (table sugar)--Glucose + fructose
• Lactose-- Glucose + galactose
Fiber
• Plant derived carbohydrate polymers and lignin
• Cannot be digested by humans enzymes
• Digested by colonic bacteria
Starch Digestion
• Phase I – Amylase digestion
• Starts with salivary amylase (ptyalin)
• Non-essential
• Pancreatic amylase
• Most significant
• Hydrolyze internal α-1,4 bonds only
• Incomplete digestion
• Results in glucose oligomers
• Maltose (dimer)
• Maltotriose (trimer)
• α-limit dextrins
• Phase II – Brush border digestion
Brush Border Digestion
• Disaccharide and oligosaccharide digestion
• Occurs on the surface of intestinal epithelial cells
• By membrane bound glycosylated carbohydrate hydrolases
• Hydrolyze to monomers
• Carbohydrates can only be absorb as monosaccharides
Cell Bio 8- Small Intestine Phase I
Carbohydrate Hydrolase Regulation
• Heavily glycosylated to protect them from pancreatic proteases
• Degraded between meals and must be resynthesized
• Sucrase, isomaltase and glucoamylase are produced in excess
• Assimilation of monosaccharides is limited by luminal transporters
Lactose Intolerance
• Lactase expression diminishes after weaning
• Natural developmental decline in lactase expression
• More common in AA’s, Asians and Hispanics
• More common in individuals without
consistent lactose in their diet
• Lactose assimilation is limited by lactase digestion
• Lactose remains in the intestinal lumen
• Retention of water
• Abdominal cramping, gas and diarrhea
Carbohydrate Absorption
• Only monosaccharides are absorbed
• Luminal transport
• Sodium/glucose transporter 1 (SGLT1)
• Glucose
• Galactose
• Against their concentration gradient
• Glucose/fructose transporter 5 (GLUT5)
• Fructose
• Not coupled to Na+
• Inefficient and can be saturated with excessive sugar intake
• GLUT5 expression can increase with increased fructose consumption
• Fructose absorption highest when combined with glucose 1:1 ratio
• Basolateral transport
• Glucose transporter 2 (GLUT2)
• Glucose
• Galactose
• Fructose
• GLUT5
• Fructose
• GLUT2 is most important
Carbohydrate Assimilation Disorders
• Mutation in the SGLT1 gene
• Rare
• Inability or decreased absorption of glucose and galactose
• Depends on the mutation
• Results in luminal retention of glucose and symptoms similar to lactose intolerance
• Diarrhea
• Abdominal cramping
Cell Bio 8- Small Intestine Phase I
•
•
•
•
Proteins
Complex polymers composed of amino acids
• 20+ different amino acids
• Dietary proteins contain 9 essential amino acids
• Cannot be synthesized de novo
Complete proteins
• Contain all of the essential amino acids
• Ex. Fish, poultry and eggs
Incomplete proteins
• Do not contain all of the essential amino acids
• Vegetables and grains
• Vegetarians must eat a variety of vegetables and soy protein
Source of allergens
• Gluten in wheat
• Casein in milk
• Multiple proteins in peanuts and seafood
Protein Digestion
 Proteins must be broken down to amino acids, dipeptides and tripeptides to be absorbed
• 4 steps
• Acid + 3 enzymatic processes
• Stomach
1. Acid hydrolysis
2. Pepsin
• Small intestine
1. Pancreatic proteases
2. Brush border peptidases
• Step 1
• Acid in the stomach can hydrolyze proteins into large peptides
• Step 2
• Pepsin catalyzed hydrolysis of proteins
1. Pepsinogen is released by chief cells of oxyntic glands
2. Pepsinogen is autocatalytically activated to pepsin at low pH
• Pepsin cleaves at proteins at neutral amino acids
1. Prefers aromatic and large aliphatic chains
2. Incomplete digestion of protein
• Leaves some intact proteins, mostly large peptides and few amino acids
Cell Bio 8- Small Intestine Phase I
•
Step 3
• Pancreatic proteases
1. Inactivate proenzymes released by the pancreas are activated by a 2 step process
Endopeptidase
• Cleave proteins only at internal bonds
• Do not release individual amino acids
Trypsin
• Specific for basic amino acids
• Leaves a C-terminus basic amino acid
Chymotrypsin and Elastases
• Specific for neutral amino acids
• Leaves a C-terminus neutral amino acid
Exopeptidases
• Cleave single amino acids form the end of a peptide chain
Carboxypeptidase A
• Specific for C-terminus neutral amino acids
Carboxypeptidase B
• Specific for C-terminus basic amino acids
So, what’s left?
Neutral and basic amino acids
Short peptides with C-terminus acidic amino acids
•
Step 4
• Brush border digestion
• Membrane bound exopeptidases including aminopeptidases and carboxypeptidases
• Further digest oligopeptides to absorbable amino acids, dipeptides and tripeptides
• Note: Some peptides just don’t go away. Peptides with proline and glycine are difficult to digest
Cell Bio 8- Small Intestine Phase I
Protein Absorption
• Dipeptides and tripeptides absorbed more efficiently than individual amino acids
• Luminal transport
• 6 different known amino acid transporters in the small intestines
• Typically non-specific
• Some specificity for neutrality and charge but still overlap
• Peptide transporter 1 (PepT1)
• Dipeptides and tripeptides
• H+ cotransporter
• Uptake peptidomimetic drugs
• Basolateral transport
• Peptides taken up by the enterocytes are digested by cytosolic peptidases
• Amino acids are transported into the plasma and lymphatic system
• Note: Whole proteins are rarely absorbed. Human babies have a short and limited ability to absorb
immunoglobulins from nursery.
Protein Assimilation Disorders
• Amino acid absorption disorders
• Don’t typically have a clinical effect on absorption
• Large redundancy in amino acid transporters
• Amino acids can be taken up as dipeptides and tripeptides
• Effect other organ systems
• Hartnup disease
• Defective transport of neutral amino acids
• Decreased absorption and reabsorption of tryptophan from the intestine and kidney
respectively
• Tryptophan is required for NAD synthesis
• Cysteinuria
• Defective transport of basic acids
• Impaired reabsorption of cysteine from the urine can lead to kidney stones