Exocrine panreatic function and biochem digestion Flashcards
List and briefly describe the end-products of macromolecule digestion
- Carbohydrates
- polysaccharides (starch eg. bread /glycogen from animals)
- disaccharides – end-product is monosaccharides
- Fats
- nearly all is triglyceride (triacyl glycerol)
– end-product is fatty acids
- nearly all is triglyceride (triacyl glycerol)
- Protein
- peptide chains of varying size
– end-product is amino acids
- peptide chains of varying size
Describe the anatomy of the SI: how is it adapted for absorption?
Small intestine
- Small intestine has a large (absorptive) surface area
- Many villous folds each containing many villi.
- Each epithelial cell contains many microvilli.
- The net result is an absorptive area of approximately 250 m2
Describe how the anatomy of the pancreas is adapted to its function
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Anatomy
- Endocrine (Islets of Langerhans)
- Exocrine (acini in lobules-> interlobular ducts into main duct) which drain into the duodenum at ampulla of Vater and the accessory duct
- inactive forms of enzymes stored into zymogen granules in acinar cells
- duct epithelial cells release HCO3, electrolytes; lots of mitochondria
List the pancreatic secretions
- Water, electrolytes and bicarbonate to neutralize the acid secretions from the stomach
- Enzymes to metabolize protein, carbohydrate and fat
List the regulators of pancreatic secretion
- Signals for release of pancreatic contents are primarily:
- Secretin: Secreted when food, esp. acid, enters duodenum
- from duodenal and jejunal mucosa
- Secretin stimulates pancreatic ductal epithelium to secrete large quantities of water and sodium bicarbonate to neutralize gastric acid
- Cholecystokinin (CCK): Secreted when food (fat and amino acids) enters duodenum
- from duodenal and jejunal mucosa
- CCK stimulates pancreatic acinar cells to secrete digestive enzymes
- Secretin: Secreted when food, esp. acid, enters duodenum
- Note: Pancreatic secretion is also mediated by vagal stimulation: releases enzymes into acini
Describe the control of pancreatic enzyme activation and autodigestion in acinar cells
**
* Proteins exist as proenzymes or zymogens
* Proteins sequestered in secretory granules – membrane is impermeable to proteins - avoid digestion of intracellular contents
* Proteins stored with inhibitors
* Conditions in secretory pathway inhibit enzyme activity
Describe the role of bile in digestion
The secretion of bile by the liver is an important part of the
digestive process
- Bile salts emulsify fat into small particles that can be digested by pancreatic lipase
- Bile salts aid in the absorption of digested fat into intestinal epithelial cells
Where are carbohdyrates digested?
- polysaccharides are digested to a small extent (5%) in the mouth by salivary gland amylase
- this continues in the stomach for some time before amylase is inactivated by the stomach acid
- Majority of digestion occurs in the small intestine by amylase secreted from the pancreas
- disaccharides are digested by enzymes on microvilli of intestinal epithelial cells (by disaccharidases)
Digestion of the macromolecules occurs in multiple areas along the GIT –> built-in redundancy.
Where are proteins digested? and what is the end product?
- Most digestion occurs in the duodenum under the action of several different pancreatic proteases.
- some protein digestion occurs in the stomach – pepsin particularly effective in digesting collagen
- Pancreatic protease digestion is not usually complete, leaving many di- and tri-peptides
- Final stage of protein digestion is by peptidases in the intestinal brush border microvilli
- Some final digestion by peptidases occurs inside enterocytes before individual amino acids are absorbed
Digestion of the macromolecules occurs in multiple areas along the GIT –> built-in redundancy.
Where is fat digested? what is the end product?
- Majority of digestion occurs in the small intestine under the action of pancreatic lipase
- small amount of fat digestion may occur in the stomach under the action of lingual lipase
- fat is hydrophobic and bile salts are needed to break the fat into small particles so that water-soluble digestive enzymes can act on the triglycerides
Digestion of the macromolecules occurs in multiple areas along the GIT –> built-in redundancy.
Describe the biochemical digestion of carbohydrates, up to absoprtion
- Substrate is dietary CH2 O (starch from plants, glycogen from animals)
- Amylase hydrolyzes α1,4 glycosidic linkages in polysaccharides
- Cellulose is a polysaccharide (poly-glucose) but joined in β1,4 links. No animal enzyme can cleave them. (Bacterial cellulase in ruminants)
- Result is a mixture of trisaccharide (maltotriose) + disaccharide (maltose) α-limit dextrin (branched oligosaccharide with α1,6 bonds)
- Salivary amylase may hydrolyze up to 25% of total starch in diet.
Carbohydrate Digestion - 2
Following digestion by salivary and pancreatic amylase, there is a mixture of oligo- and di-saccharides. These are metabolized by disaccharidases located in the brush borders of the intestinal enterocytes. The end result is the production of monosaccharides, which can be absorbed by the intestinal mucosa. For persons on a normal diet, glucose accounts for approximately 80% of the final monosaccharides available for absorption.
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- lactose —> glucose and galactose
- maltose –> 2 glucose
- sucrose —> glucose and fructose
Glucose is absorbed in association with sodium (3Na/2K, makes intracellular environment more negative, which drives passive Na/glucose symporter – which also transports galactose. Absorbed into blood by glucose/fructose transporters).
Firstly sodium is transported from the intestinal epithelial cell into the blood.
Secondly, in response to reduced epithelial cell sodium, sodium is absorbed from the intestine by facilitated diffusion, bound to a transport protein.
This transport protein will not move into the cell without glucose.
Galactose is absorbed in similar fashion to glucose.
Fructose is absorbed by facilitated diffusion via a sodium-
independent process.
Describe the biochemical process of protein digestion up to absorption
- The total protein load in the gastrointestinal tract per day is:
- Dietary: 70 - 100 g per day (adult)
- Endogenous: 35 – 200 g (enzymes, other proteins, cell turnover).
- Digestion is efficient, usually resulting in only 6-12 g of protein in feces.
- Two types of proteolysis are described:
- Trypsin and chymotrypsin split proteins into smaller peptides.
- Carboxypeptidase cleaves proteins to individual amino acids.
- The net end products are amino acids, di- and tri-peptides.
- Sites of action of the peptidases are very specific e.g. chemotrypsin and hydrophobic pocket (Phe), trypsin and salt bridges (Lys), elastase small hydrophobic pocket (Gly)
Protein Digestion - 2
- Proteases (peptidases) are generally secreted into the lumen in an inactive form.
- The active form is produced either by a pH change (e.g., pepsinogen B) or by HCl itself (pepsinogen A) in the stomach. Pancreatic trypsinogen needs duodenal entero-peptidase or (-kinase).
- Trypsin’s central role is the activation of other pancreatic peptidases.
- Notably, trypsin inhibitor is secreted in the pancreas in concert.
- HCO3– is important for optimal protease activity.
- Membrane-bound endopeptidases, dipeptidases, and aminopeptidases convert peptides to amino acids.
- Absorption of amino acids by very specific carriers (similar in renal tubular epithelium).
Descrbe the biocehmical aspect of lipid digestion and absorption
- 90% of dietary fat is triglyceride (TG), with the remainder being cholesterol, cholesterol ester, phospholipid, and free fatty acids (FFA).
- The primary site of lipid digestion is in the duodenum, requiring fat to be highly emulsified with bile salts and lecithin.
- (TAG) Lipase released from the pancreas hydrolyzes TG to monoglycerides and FFA, requiring co-lipase for activity.
- Co-lipase binds to water-lipid interface (on globule surface, of micelle) and simultaneously activates lipase
Lipid Absorption
- Absorption occurs in the jejunum, where micelles deliver lipid digest to the brush border.
- FFA eg glycerol and 2-mono-acylglyceride (MAG) are taken up into enterocytes by diffusion because they are lipid-soluble.
- 2MAG used for re-synthesis of TAGs, by fatty acid CoA ligase, using long chain fatty acids
- Within enterocytes, absorbed FFA are converted predominantly to triglycerides, which are released into thoracic duct lymph as chylomicrons – for long chain FAs.
- Some short chain fatty acids are absorbed directly into portal blood
Descrieb the role of lymphatics in dgestion and absorption
- The lymphatics drain excess fluid and secretions from the interstitial spaces.
- Especially important is the ability to carry proteins, large molecules, and particulate matter from tissue spaces.
- Lymphatic drainage from the gut empties into the thoracic duct, which drains into the left internal jugular vein at the junction with the left subclavian vein.
List some conditions that affect nutrient absorption
- Cholecystitis - fat malabsorption (no emulsification)
- Chronic Pancreatitis - maldigestion of macromolecules, excreted in stool; steatorrhea; malnutrition
- Lactase Deficiency - fermentation, bloating, diarrhoea
- Gluten Intolerance - destruction of gut epithelial cells, loss of small peptidases, disaccharases –> malabsorption, diarrhoea, bloating
- Cystic Fibrosis - less fluids - malabsorption, nutritional deficiency
- Liver Disease - malabsoprtion; congestion if portal hypertension
- Crohn’s Disease - malabosoption, bloating/fermentation, diarrhoea
