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TPTC2 > GI Therapeutics - transport mechanisms in the GI tract > Flashcards

GI Therapeutics - transport mechanisms in the GI tract Flashcards

1
Q

Digestion and Absorption: Summary

A

• Pancreatic enzymes cannot digest all nutrients
• Final digestion takes place on the lumenal surface of enterocytyes which are epithelial cells that line GI tract
- Brush border enzymes on enterocytes
• Intracellular digestion in enterocytes
- Absorption and hydrolysis of di- and tripeptides
• Digestive enzymes are secreted as pro enzymes
• Secretion is regulated by many secretagogues

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2
Q

Examples of secretagogues

A

• Acetylcholine -
neurotransmitter that is secreted from para sympathetic neurons
• Histamine - secreted from secretory cells with GI tract
• Gastrin - secreted from secretory cells with GI tract
• Secretin - secreted from secretory cells with GI tract

-regulatory factors

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3
Q

Carbohydrates and Proteins -

A
  • enzymes breakdown carbohydrates into monosaccharides and proteins into AAs - pancreatic anzyme, intestinal enzyme
  • monosaccharides are absorbed into enterocyte via active transport
  • via facilitated diffusion AAs and monosaccharides move out of the enterocyte
  • Via diffusion they enter the capillary to hepatic portal system to build proteins or provide energy
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4
Q

What is the hepatic portal system

A

blood vessels that run from the gut to the liver

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5
Q

Lipids

A
  • fat globules (lipids) churned up in stomach
  • bile salts attach onto the globules to form emulsion droplets which have a large SA: Vol
  • emulsion droplets are digested by lipases in the intestinal lumen and converted into free fatty acids (monoglycerides) and bile salts
  • they then form micelles and bile salts
  • the micelles enter enterocyte and become triglyceride and bind with proteins to form chylomicrons
  • secreted into vesicles into lacteal
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6
Q

What is the lacteal

A

part of lymphatic system

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7
Q

Digestive Enzymes Organ:

Enzymes:

A

Organ: Salivary glands
Enzymes: Amylase, Lysozyme

  • amylase is used to break down starch into shorter oligosacchairde chain
  • lysozyme remove some polysaccharide chain from bacteria which stops them from interacting with each other and multiplying
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8
Q

Digestive Enzymes Organ:

Enzymes:

A

Organ: Stomach
Enzymes: Pepsin A, Gastric lipase

  • pepsin a is a portease enzyme, pepsinogen (inactive pro enzyme)
  • gastric lipase breaks down triglycerides into monoglycerides
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9
Q

Digestive Enzymes Organ:

Enzymes:

A

Organ: Pancreas
Enzymes: Trypsin, Chymotripsin, Elastase, Carboxypeptidase A, Carboxypeptidase B, Pancreatic lipase

All break down proteins

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10
Q

Where are enzymes mostly secreted from

A

Pancreas

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11
Q

Enzymes of the Brush Border

A

Brush Border Enzyme

  • Maltase
  • Sucrase
  • Glucoamylase
  • Trehalase
  • b-Glucosidase
  • Lactase
  • Endopeptidase
  • Aminopeptidase A
  • Aminopeptidase N
  • Dipeptidyl aminopeptidase IV
  • Leucine aminopeptidase
  • gamma-Glutamyltransferase
  • Enteropeptidase
  • Alkaline phosphatase

Substrate

  • Maltose
  • Sucrose
  • Amylose
  • Trahalose
  • Glucosylceramide
  • Lactose
  • Protein
  • Oligopeptide
  • Oligopeptide
  • Oligopeptide
  • Peptides
  • Glutathione + amino acid -Trypsinogen (turns into active trysin)
  • Organic phosphates
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12
Q

Which brush border enzymes break down carbohydrates to simpler carbohydrates

A
  • Maltase
  • Sucrase
  • Glucoamylase
  • Trehalase
  • b-Glucosidase
  • Lactase
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13
Q

Which brush border enzymes break down proteins

A
  • Endopeptidase
  • Aminopeptidase A
  • Aminopeptidase N
  • Dipeptidyl aminopeptidase IV
  • Leucine aminopeptidase
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14
Q

SI Epithelial Cells (Enterocytes) - Lumenal

A

-Morphological appearance - Ordered microvilli (brush border)
-Enzymes - Di- and oligosaccharidases, Aminopeptidase, Dipeptidases, gamma-Glutamyltransferase, Alkaline phosphatase, Guanylate cyclase
(all help in digesting food)
-Transport systems - Na+-monosaccharide cotransport (SGLT-1), Facilitated fructose transport (GLUT-5) , Na+-neutral amino acid cotransport, Na+-bile cotransport (ASBT),
H+-peptide cotransport (PepT1)

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15
Q

SI Epithelial Cells (Enterocytes) -

Contralumenal

A
  • Morphological appearance - Few microvilli
    -Enzymes - Na+/K+ ATPase (provides driving force for absorption of digested micro nutrients), Adenylate cyclase
    -Transport systems - Facilitated monosaccharide transport (GLUT-2),
    Facilitated neutral amino acid transport
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16
Q

Na+/K+ ATPase: the engine for endothelial transport

A

most important enzyme in this process
-Lumen of GI tract - where digested food is

draw diagram slide 10

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17
Q

Na+/K+ ATPase: the engine for intestinal uptake

A

• Na+/K+ ATPase creates an electrochemical gradient with low Na+ inside the cell
– Similar to potential difference in an electrical circuit
• Array of channels and transporters on lumenal and capillary sides of epithelium
– Allows Na+/K+ ATPase to drive a range of different transport processes

18
Q

In the large Intestine, Cl- follows the current created by Na+/K+ ATPase

A

-main purpose of LI is to remove water from stuff eaten - if it doesn’t work leads to diarrhoea

19
Q

what is Cl- used for

A

surrogate for water transport across GI membrane

draw diagram - slide 12

20
Q

In the large Intestine, Cl- follows the current created by Na+/K+ ATPase

A

• Epithelial Na+ Channel allows lumenal Na+ ions to flow into cell
– Down electrochemical gradient
– Creates an electrical potential across the lumenal
membrane
• Chloride ions flow into the cell to neutralise this potential difference
– Passive, uncoupled chloride channel

21
Q

In the small intestine, Na+/K+ ATPase is coupled to electrically neutral Na+ and Cl- transport

A
  • CA turning water and co2 into bicarbonate ions and protons in the inside and those are pumped out by the DRA and NHE3
  • CA recombines them to and splits them into co2 and water so co2 can flow across the membrane
  • draw diagram slide 14
22
Q

Small intestine Na+/K+ ATPase coupled

to neutral Na+ and Cl- transport

A

• Na+ entry coupled to H+ efflux via coupled Na+/H+ antiport
– H+ provided via carbonic anhydrase
• Carbonic anhydrase also creates HCO3- ions
– HCO3- gradient drives Cl- uptake via another antiport

23
Q

Na+/K+ ATPase drives NaCl secretion as well as uptake – no Na+ channel on lumenal membrane

A
  • sometimes water needs to be moved into the gut

- draw diagram slide 16

24
Q

What happens in Cystic fibrosis

A
  • in cystic fibrosis CFTR breaks down
25
Q

Cystic Fibrosis

A
  • An autosomal recessive hereditary disease affecting the lungs, sweat glands and the digestive system
  • Cl- transport is severely impaired in CF sufferers
  • ~1 in every 25 caucasians carries the CF gene, each having one ‘normal’ gene and one CF gene
  • CF carriers enjoy some protection against cholera
  • Natural response is for GI epithelial cells to open their Cl- channels, causing loss of water
  • CF carriers are at reduced risk of dehydration as less fluid is released to clear the bacteria, avoiding diarrhoea
26
Q

Na+/K+ ATPase drives NaCl secretion as well as uptake

A

• In this system, there is no Na+ channel in the lumenal membrane
• Na+/K+ ATPase drives high cellular Cl- levels via the Na+/K+/2Cl- cotransporter
– Found on capillary membrane
• Cl- flows into lumen via CFTR
– High lumenal Cl- creates electrical potential
– Draws Na+ into lumen via paracellular route

27
Q

Absorption: Carbohydrates

A

draw diagram - slide 20

28
Q

‘Uphill’ Glucose Transport

A

active transport system

draw diagram - slide 21

29
Q

Absorption: Peptides

A

Draw diagram - slide 22

30
Q

Absorption: Lipids

A

Draw diagram - slide 23

31
Q

Absorption: Lipids -What does digestion mean

A

digestion means the breakage of the ester bonds between glycerol and fatty acid elements of triglyceride to break that down into free fatty acids and monoglycerides (glycerol molecule with a single fatty acid in 2 position)

32
Q

What is the environment of intestinal lumen

A

aq enviornment

33
Q

What are bile salts

A

bile salts = detergents for ingested fats, help to dissolve fats by binding to the outside of the fat globules. increases SA and allows digestion

34
Q

Digestion and Absorption of Lipids

A

Draw diagram - slide 24

35
Q

Bile salts

A

• Cholesterol derivatives secreted from the liver
– Important role in solubilising lipids and aiding absorption
• Recirculated between the liver and the intestine
– Secreted from liver in bile; form micelles in small intestine; reabsorbed in distal ileum nearest to LI
– 20-30g secreted in bile/day; total amount in body only 3-5g (non toxic amount)
– Important as bile salts toxic at high concentrations

36
Q

Enterohepatic circulation of bile acids

A

Diagram - slide 26

37
Q

TC and PC during enterohepatic circulation

A

Diagram - slide 27

38
Q

Enterohepatic Circulation and Xenobiotics

A
  • Xenobiotics conjugated by excreted via biliary route.
  • Enterohepatic recirculation delays the elimination of xenobiotics and can increase toxicity. (particularly hepatic toxicity)
39
Q

GI-tract pathology

A

• Acid-related disorders
– Peptic ulcers; gastroesophageal reflux disease
• ChronicBowelDisorders
– Irritable Bowel Syndrome (recurrent abdominal pain; no clear pathology or etiology)
– Inflammatory Bowel Diseases
• No single cause of disease: hereditary; autoimmune disorder; stress and trauma; diet
• Inflammation of mucosa and submucosa
• Ulcerative colitis – large intestine
• Crohn’s disease - any part of GI system

40
Q

Summary

A
  • The absorption and transport of nutrients across the GI epithelial cells is a complex process that involves both active and passive diffusion
  • For peptides, digestion continues within the cell after the nutrients have been absorbed
  • Fats are absorbed and transported using a different circulatory system and are associated with bile within the lumen of the GI tract

TPTC2 (8 decks)

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