26-01-23 - Gastrointestinal digestion & absorption

Question 1

Learning outcomes

Answer 1

• Recall the main sources of nutrition
• Define “digestion” and “absorption” in the context of human nutrition and physiology
• Explain how the structure of the small intestine is adapted for efficient absorption
• Explain how and where carbohydrates, lipids and proteins are digested
• Define and compare and contrast the terms “chylomicron” and “micelle”
• Explain how bile salts are used in lipid digestion and why it is necessary
• Outline how bile salts are recirculated
• Explain how products of digestion and water are absorbed

Question 2

What is digestion?

What is absorption?

Answer 2

• Digestion - the breakdown of nutrients into absorbable molecules
• Absorption - movement of nutrients, water and electrolytes from the gut lumen into the internal environment

Question 3

How is the surface of the small intestine arranged?

Where do villi project from?

What us the surface of the villi covered with?

What is the apical surface of epithelial cells covered with?

Answer 3

• The surface of the small intestine is arranged in circular folds of Keckring
• Villi project from the folds
• The surface of the villi are covered with epithelial cells (enterocytes) with mucus secreting cells (goblet cells)
• The apical surface of epithelial cells covered by microvilli – brush border

Question 4

How much carbohydrates, lipids, and protein do we ingest on average?

What are 4 types of carbohydrates?

What are 5 types of lipids?

What proteins do we consume endogenously?

Answer 4

• Carbohydrates – c. 250-800 g/day
• 4 types of carbohydrates:
  1) Starch
  2) Glycogen
  3) Cellulose
  4) Disaccharides
• Lipids – c. 25-160 g/day
• 5 types of lipids:
  1) Triacylglycerols (TAG) 90% (fats, oils) [Triglycerides]
  2) Phospholipids
  3) Cholesterol & cholesterol esters
  4) Free fatty acids
  5) Lipid vitamins
• Proteins – c. 70-100 g/day ingested - + 35-200g from endogenous sources
• e.g. endogenous sources - digestive enzymes & dead cells from GI tract

Question 5

Other dietary requirements.

What 4 fat soluble vitamins do we also require?

What 9 water soluble vitamins do we require?

What are 6 minerals (trace metals) we require?

Why do we need these vitamins and minerals in our diet?

What processes can they be used for in the body?

What can deficiencies result in?

What are 3 examples of pathologies from deficiencies?

Why should be stick to recommended doses?

Answer 5

• Other dietary requirements
• 4 fat soluble vitamins do we also require - A, D, E, K
• 9 water soluble vitamins do we require - B1,2,3,5,6,12, folate, biotin, C
• 6 minerals (trace metals) we require - Ca, Fe, Zn, Mn, Mg, Phosphorous, etc
• We need vitamins and mineral in our diet because they are not produced by the body (or endogenous amounts not sufficient)
• May be required as cofactors, antioxidants, “hormone” (vit D – synthesised in liver in sunlight, but required in diet if not exposed)
• Deficiencies result in well documented pathologies
• 3 examples of pathologies from deficiencies:
  1) Rickets (D)
  2) Scurvy (C)
  3) Anaemia (B12)
• Vitamins and minerals may be cytotoxic in increased concentrations, therefore stick to RDA (Recommended Dietary Allowances)

Question 6

How much digestion and absorption occurs at each part of the digestive tract?

What is absorbed at each stage?

What 6 things do we need to digest and absorb?

Answer 6

• How much digestion and absorption occurs at each part of the digestive tract:

1) Mouth
* Very little digestion – small amount of lipids and carbohydrates
* Almost no absorption (certain drugs)

2) Stomach
* Some digestion – proteins, but not very important
* Almost no absorption (certain drugs)

3) Small intestine
* Lots of digestion and absorption – carbohydrates, lipid, protein
* Vital site of digestion and absorption, (some regional differences between duo, ileum, jejunum)

4) Large intestine
* Almost no digestion/absorption (apart from water)
* Some “indigestible” e.g corn substances used as fuel by gut flora

• 6 things do we need to digest and absorb:
  1) Carbohydrate
  2) Lipid
  3) Protein
  4) Water
  5) Vitamins
  6) Minerals

Question 7

Which carbohydrates can be absorbed in the small intestine?

What does digestion of carbohydrates begin with in the digestive tract?

Answer 7

• The only carbohydrates that can be absorbed in the small intestine are monosaccharides e.g fructose, glucose and galactose.
• The rest have to be broken down into monosaccharides
• Fructose is absorbed via facilitate diffusion in the small intestine
• Galactose and glucose are absorbed via Na+-dependant cotransport in the small intestine
• Digestion of carbohydrates in the in the digestive tract begins with salivary alpha-amylase (minor role)

Question 8

What are the 3 locations carbohydrates are digested?

How are they digested in each location?

What causes lactose intolerance?

Answer 8

• The 3 locations carbohydrates are digested:

1) Mouth
* Carbs digested by Salivary α amylase

2) Stomach
* α amylase from the mouth continue to act
* This is because salivary alpha amylase stays in the bolus for a small amount of time before being denatured by pH2 of the stomach

3) Duodenum
* Carbs digested by pancreatic amylase
* Brush border enzymes (maltase, sucrase & lactase) - act on disaccharides, producing monosaccharides-fructose, glucose & galactose

• Lactose intolerance - no lactase enzyme so bacteria ferment sugar (lactose), which causes gas & diarrhoea

Question 9

Which carbohydrates are digestible and non-digestible?

What do they consist of?

Answer 9

• Digestable carbohydrates:
  1) Starch (from plants)
  2) Glycogen (from animals)
• These consist of linear chains of glucose molecules joined by α 1-4 glycosidic bonds initially digested by amylase
• Non-digestible carbohydrates:
  1) Cellulose (from plants)
• Consist of linear chains linked by β 1-4 glycosidic bonds.
• No enzymes in humans to digest cellulose

Question 10

What are amylases?

Where are they found?

What do they digest?

What are the 2 types of amylases?

What 3 products do amylases breakdown polysaccharides into?

What forms the cross-links between polymeric chains in α-limit dextrin?

Answer 10

• Amylases are free enzymes acting in the GI lumen and digest only internal α-1-4 glycosidic bonds of polysaccharides
• 2 types of amylases:

1) Salivary amylases
* Secreted from mouth in response to sight & smell of food - of lesser importance than

2) Pancreatic amylases
* Secreted from pancreas into duodenum

• 3 products amylases breakdown polysaccharides into:
  1) Maltose
  2) α-limit dextrin
  3) Maltotriose
• Cross-links between polymeric chains in α-limit dextrin are formed by α-1-6 bonds

Question 11

What are products of amylase digested by?

Where are these located?

What are 2 examples of oligosaccharidases?

What do they each cleave?

Answer 11

• Products of amylase – now digested by oligosaccharidases, which are carbohydrases (attached to the enterocyte mucosal membrane of the brush border of epithelial cells)
• 2 examples of oligosaccharidases:

1) α-glucosidase
* Cleaves α-1-4 glycosidic bonds to remove single glucose units from the non-reducing end of the polymer

2) Isomaltase
* Cleaves α-1-6 glycosidic bonds in the α-limit dextrin oligosaccharides

Question 12

What are products of amylase and oligosaccharidases are hydrolysed by?

Where are disaccharidases found?

What are 3 examples of disaccharidases?

What do they each digested and form?

What bonds do they each digest?

Answer 12

• Products of amylase and oligosaccharidases are hydrolysed by the disaccharidases which are attached to the brush border membrane
• 3 examples of disaccharidases:

1) Maltase – produces glucose
* Maltase breaks down maltose into glucose
* Maltose consists of 2 glucose molecules
* α 1-4 glycosidic bond connecting the 2 glucose molecules is digested by maltose

2) Sucrase – produces glucose & fructose
* Sucrase breaks down sucrose into glucose and fructose
* α 1-2 glycosidic bond connecting the glucose and fructose together is digested by sucrase

3) Lactase – produces galactose & glucose
* Lactase breaks down lactose into galactose and glucose
* beta 1-4 glycosidic bond connecting the galactose and glucose is digested by lactase

Question 13

What are the 3 final products of carbohydrate digestions?

Answer 13

• 3 final products of carbohydrate digestions:
  1) Glucose
  2) Galactose
  3) Fructose

Question 14

What 2 ways are carbohydrates absorbed?

Answer 14

• 2 ways are carbohydrates absorbed:

1) Secondary active transport
* SGLT 1 (sodium dependent glucose transporter 1) located on the apical membrane transports glucose and galactose

2) Facilitated diffusion
* GLUT 5 (glucose transporter 5) transports fructose across the apical membrane
 

Question 15

Overview of carbohydrate digestion and absorption diagram

Answer 15

Question 16

Where does protein digestion begin?

Where is it completed?

What are the roles of endopeptidases and exopeptidases?

In what form are proteases secreted?

Answer 16

• Protein digestion begins in the stomach with pepsin
• Protein digestion is completed in the small intestine with pancreatic and brush-border proteases
• Endopeptidases hydrolyse the interior peptide bonds of proteins
• Exopeptidases hydrolyse one amino acid at a time from
• Proteases are secreted in an inactive form as zymogens before being activated

Question 17

What Is the role of endopeptidases?

What are 4 examples of endopeptidases?

What do they each cleave?

Answer 17

• Endopeptidases cleave large polypeptides in middle of chain oligopeptides (2-8 AA long)
• 4 examples of endopeptidases:

1) Pepsin (stomach)
* Hydrolyses links with tyrosine, D alanine & leucine
* Hydrolyses long polypeptide chains into shorter ones

2) Trypsin (SI)
* Hydrolyses links with arginine & lysine
* Trypsin inhibitor - Protection of self
* Trypsin inhibitor is a small protein present in pancreatic juice to inhibit any trypsin found prematurely in the pancreatic cells or duct

3) Chymotrypsin (SI)
* Hydrolyses links with tyrosine, tryptophan, D alanine, methionine & leucine

4) Elastase (SI)
* Degrades elastin

Question 18

What is the role of exopeptidases?

What are 2 examples of exopeptidases?

Answer 18

• The role of exopeptidases is to cleave amino acids one at a time from either end of protein
• 2 examples of exopeptidases:

1) Carboxypeptidases (C-terminal)

2) Aminopeptidases (N-terminal)

Question 19

What are the 2 Products of stomach and pancreatic luminal enzymes?

How does protein digestion continue?

What are 2 example of brush border enzymes?

What are the 3 products of protein digestion?

What occurs to these products in the enterocytes?

What are enterocytes?

Answer 19

• 2 Products of stomach and pancreatic luminal enzymes:
  1) Oligopeptides
  2) Amino acids
• Protein digestion continues via 2 brush border enzymes:
  1) Oligopeptidase
  2) Aminopeptidase
• 3 products of protein digestion:
  1) Amino acids
  2) Dipeptides
  3) Tripeptides
• In enterocytes, these products are further broken down to AAs
• Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines

Question 20

Describe the 3 different phases of protein digestion.

Which enzymes are used at each phase?

What is digested at each phase?

Answer 20

• 3 different phases of protein digestion:

1) Gastric phase
* Denaturation by HCl
* Pepsin in the stomach used for digestion

2) Pancreatic phase (small intestine)
* Trypin, chymotrypsin, and carboxypeptidase used
* Oligopeptides (2-8 residues) broken down into amino acids

3) Mucosal phase
* Oligopeptidase and aminopeptidase used for digestion
* Dipeptides and tripeptides broken down into amino acids

Question 21

How are the 3 products of protein digestion absorbed in the small intestine?

Answer 21

• How the 3 products of protein digestion absorbed in the small intestine:

1) Amino acids
* Na+-dependant cotransport

2) Dipeptides
* H+-dipeptide cotransport

3) Tripeptides
* H+-tripeptide cotransport

Question 22

Overview of peptide & AA digestion and absorption diagram.

What is an important exception to this?

Answer 22

• Overview of peptide & AA digestion and absorption diagram
• An important exception to the peptide and AA absorption and digestion is immunoglobulins in breast milk, which can be absorbed in their active form to confer immunity In a new-born

Question 23

Why do dietary lipids cause problems with digestion?

What must happen before they can be digested and absorbed?

Where does digestion of lipids start?

Where is digestion of lipids completed?

Answer 23

• Dietary lipids are hydrophobic (insoluble in water) so causes problems with digestion & absorption
• They must be solubilised before digestion and absorption can occur
• Digestion begins in the stomach with the action of lingual and gastric lipases
• Digestion is completed in the small intestine with the action of the pancreatic enzymes

Question 24

What are the 4 main types of lipids?

Which one makes up >90% of lipid intake?

Answer 24

• 4 main types of lipids:

1) Triacylglycerols (TAG or triglycerides)
* >90% of lipid intake
* Consist of glycerol backbone (hydrophilic) and 3 fatty acid tail groups (hydrophobic)

2) Phospholipids

3) Cholesterol & cholesterol esters

4) Fatty acids

Question 25

What are 3 main types of enzymes for lipid digestion? What are bile salts important for?

Answer 25

* 3 main types of enzymes for lipid digestion: 1) Lipases 2) Phospholipases 3) Cholesterol esterases * Bile salts also have important role in achieving digestion/absorption, but are not enzymic

Question 26

What 2 locations does lipid digestion of TAG by lipases occur? What lipases are used at each location? Describe the 4 steps in TAG digestion by lipases in the mouth/stomach. What aids TAG digestion in the duodenum?

Answer 26

* 2 locations lipid digestion of TAG by lipases occurs: 1) In (mouth) & stomach * Salivary / gastric lipases (-relatively unimportant ~10% of ingested lipids hydrolysed) used here * 4 steps in TAG digestion by lipases in the mouth/stomach: 1) Heat & movements in stomach mix food with lipases lipid emulsion 2) Hydrolysis initially slow due to largely separate aqueous/lipid interface 3) As hydrolysis proceeds, rate increases due to fatty acids produced acting as surfactants breaking down lipid globules aiding emulsification 4) Emulsified fats ejected from stomach to duodenum 2) In duodenum * Pancreatic lipase (-important- the main lipid digestive enzyme) used here * Aided by bile salts from gall bladder * HCO3 - neutralises stomach acid leading to suitable pH

Question 27

Digestion of lipids in the small intestine. What 3 substances emulsify dietary lipids in the small intestine? How does emulsification aid in pancreatic enzyme digestion? What 3 pancreatic enzymes are used to complete digestion of lipids in the small intestine? What protein is also secreted?

Answer 27

* Digestion of lipids in the small intestine * 3 substances that emulsify dietary lipids in the small intestine: 1) Bile salts 2) Lysolecithin 3) Products of lipid digestion * Emulsification produces small droplets of lipids dispersed in an aqueous solution creating a large surface area for pancreatic enzyme digestion * 3 pancreatic enzymes are used to complete digestion of lipids in the small intestine: 1) Pancreatic lipase 2) Cholesterol ester hydrolase 3) Phospholipase A2 * The protein colipase is also secreted to complete digestion in the small intestine

Question 28

Role of bile salts in emulsions What do bile salts covering lipids form? What 2 sides is there to the bile salts? What are micelles? What do they consist of? What 5 products of lipid digestion do micelles contain?

Answer 28

* The role of bile salts in emulsions: * Bile salts coat lipid droplets to make emulsions that are solubilised in watery component of the stomach * There is a hydrophobic side of the bile salt associated with the lipid and a hydrophilic side of the bile salt associated with water due to the polar side chains it contains * Micelles are small (diameter - 5nm) disks with a bile salt amphipathic (hydrophilic and hydrophobic parts) surface and a core of products of lipid digestion * This allows the products of lipid digestion to be solubilised * 5 products of lipid digestion do micelles contain: 1) Cholesterol 2) Monoglycerides 3) Diglycerides 4) lysolecithin 5) Free fatty acids

Question 29

Describe the 6 steps in the digestions and absorption of lipids in the small intestine

Answer 29

* 6 steps in the digestions and absorption of lipids: 1) Bile salts from the liver coat fat droplets * Small lipid droplets become emulsified (solubilised) in the aqueous environment when the bile salts and other products of bile coat the outside of lipid particles 2) Pancreatic lipase and colipase break down fats into monoglycerides and fatty acids which are stored in micelles. * Colipase is a protein co-enzyme associated with micelles * It can hold onto micelles and a lipase and bring the structures together, making the digestion easier 3) Monoglycerides and fatty acids move out of micelles and enter cells enterocytes) by diffusion * The whole micelles doesn’t move into the cells, just the breakdown products * The more breakdown products are adsorbed as lipids move down the small intestine, the more bile salts are recycled to the liver 4) Cholesterol in micelles is transported into cells by a membrane transporter as it is bigger 5) Absorbed fats combine with cholesterol and proteins in the intestinal cells to form chylomicrons. * Chylomicrons are a mixture of breakdown products * Micelles are free floating in the lumen of the small intestine while chylomicrons are formed in the enterocytes (don’t confuse the 2) 6) Chylomicrons are released into the lymphatic system via exocytosis through the basolateral borders of the enterocytes * This is because chylomicrons cant pass directly into capillaries, so much go into the lymph system, the thoracic duct, internal jugular vein, then into circulation * This is why lymph will be cloudy after a meal  

Question 30

How large are chylomicrons? What does their core and outside consist of? How do chylomicrons exit enterocytes? Where do chylomicrons enter into? Where do chylomicrons travel to from here?

Answer 30

* Chylomicrons are 100 nm in diameter * They have a core of triglycerides and cholesterol ester - phospholipids and apoproteins on the outside (80%/20%) * Chylomicrons exit enterocytes by being packaged into secretory vesicles on the Golgi membrane and exocytosed across the basolateral membrane * Chylomicrons are too big to enter vascular capillaries but enter the lymphatic capillaries (lacteals) by moving between the endothelial cells that line the lacteals * The lymphatic circulation carries the chylomicrons to the thoracic duct which empties into the blood stream

Question 31

How many grams of bile salts are required per meal? How many grams are in the body? What happens after bile salts are used? What % of bile salts are recycled?

Answer 31

* ~3-4 g of bile salts in body, but ~3-15g required per meal * After use, most reabsorbed from terminal ileum into the liver via enterohepatic circulation (via hepatic portal vein) * 95% of bile salts are recycled and 5% are lost in faeces

Question 32

Lipid absorption summary

Answer 32

Question 33

Overview of lipid digestion and absorption summary

Answer 33

Question 34

What 6 substances are absorbed in the large intestine? How are they each absorbed? What 2 ways is absorption controlled in the large intestine?

Answer 34

* 6 substances are absorbed in the large intestine: 1) Absorption of H2O (& NaCl) * Mechanisms complex and not fully understood 2) Na+ actively absorbed (in exchange for K+) 3) K+ reabsorbed in exchange for H+ 4) Cl- absorbed (in exchange for HCO3 -) 5) H2O follows due to osmosis * 2 ways is absorption controlled in the large intestine: 1) Enteric nerve plexi 2) Hormonal control * Aldosterone (↑ water abs)

Question 35

How can bacteria thrive in the large intestine? What are 3 roles of bacteria in the large intestine? What 3 B vitamins are formed in the large intestine? How are vitamin B and K absorbed in the large intestine?

Answer 35

* Bacteria can thrive in the large intestine as movement through the LI is very slow (10^11 bacteria / g faeces) * 3 roles of bacteria in the large intestine: 1) Formation of certain B vitamins * B12 * Thiamin * Riboflavin 2) Formation of vitamin K * B and K absorbed passively (probably –mechanisms remain uncertain) 3) “Digestion” * Bacteria feed off of certain bile constituents and other “indigestible” matter e.g sweetcorn

Question 36

How much fluid enters the GIT tract each day? How much is from ingestion and secretion? How much liquid does the small intestine absorb? How much does the large intestine absorb? How does it do this? How much water does faecal mater contain? How can substances not supposed to be present in the large intestine affect its function?

Answer 36

* ~ 9L of fluid enters GI tract each day * Approximately 2.3L from ingestion, the rest from secretion) * The small intestine reabsorbs ~ 8L * The large intestine reabsorbs ~ 90% of the last litre by osmosis through cell walls into vascular capillaries inside villi * Faecal matter contains about 100mls of water * Substances not supposed to be in the large intestine (such as lactose) can affect its function by altering the osmotic environment * This can result in les water absorption or osmotic movement into the large intestine, causing diarrhoea

Question 37

Summary of absorption of major nutrients in small intestine diagram

Answer 37

Question 38

Digestion and Absorption - summary

Answer 38