digestion and absorption of nutrients (lecture series) Flashcards
(107 cards)
1
Q
What are proteins broken down (digested) into ?
A
- amino acids
- dipeptides
- tripeptides
2
Q
What are carbohydrates (polysaccharides) broken down (digested) into ?
A
monosaccharides
3
Q
Where are the enzymes found that digest proteins?
A
- stomach
- pancrease
- brush border
4
Q
Where are the enzymes found that digest carbohydrates?
A
- saliva
- pancreas
- brush border
5
Q
Where are the enzymes found that digest fats?
A
- stomach
- pancreas
- bile salts
6
Q
What are fats (triglycerides) broken down (digested) into ?
A
- free fatty acids
- glycerol (monoglycerides)
7
Q
What is another name for carbohydrates ?
A
polysaccharides / disaccharides
8
Q
What is/causes malabsorption ?
A
incomplete digestion of large molecules into smaller ones (e.g proteins into amino acids)
9
Q
How does malabsorption cause diarrhoea ?
A
- incomplete digestion
- large molecules continue to move through GI tract
-
large molecules draw water with them
= stool is loose
10
Q
What are the main methods of absorption ?
A
- simple diffusion
- carrier mediated (facilitated diffusion, secondary active transport)
- receptor-mediated endocytosis (vit B12, intrinsic factor, cholesterol)
11
Q
Where does the majority of absorption take place ?
A
duodenum
jejunum
12
Q
Which substances are absorbed in the terminal ileum ?
A
- vitamin B12
- bile salts
- potassium
13
Q
Which substances are absorbed in the colon ?
A
- sodium
- some water
- short chain fatty acids
14
Q
Which sites in the GI tract are only involved in very limited absorption of nutrients ?
A
- mouth
- oesophagus
- stomach
- rectum
15
Q
What is the benefit of delivering drugs via mouth or rectum?
A
the blood supply from these areas go to the heart whereas the blood from the intestines go via the liver
16
Q
What are the 2 main features of the small intestine that make it the major site of absorption ?
A
- surface area (200m^2 total area)
- polarised expression of transport proteins used in absorption
17
Q
What features of the small intestine create such a large surface area?
A
- Plicae circularis/folds of kerckring= circular folds in the wall
- villi
- microvilli = “brush border”
18
Q
What does “polarised expression of transport proteins” mean ?
A
there are different ion transports on each side of the cell meaning that a gradient can be formed
19
Q
What is another name for co-transport ?
A
secondary active transport
20
Q
What drives co-transport/secondary active transport ?
A
usually, an Na gradient created by the sodium-potassium pump on the opposite membrane
21
Q
What physical problems can cause malabsorption ?
A
- indigestion (lack of enzymes)
- decreased surface area
- lack of transporters
22
Q
What is the co-transport protein for glucose called ?
A
SGLT1 protein
23
Q
What is the protein transporter for fructose called that’s in the apical intestinal membrane ?
A
GLUT5
24
Q
What is the protein transporter for fructose called that’s in the basement intestinal membrane ?
A
GLUT2
25
What is glucose-galactose malabsorption syndrome ?
- **genetic** disease
- **SGLT1 mutation** (glucose co-transporter protein on apical membrane)
= **cannot absorb glucose** or galactose in the intestines
26
How does glucose-galactose malabsorption syndrome manifest/present in infants?
**Severe/potentially fatal diarrhoea**
= child becomes malnourished and quickly dehydrated
27
What is the treatment for glucose-galactose malabsorption syndrome ?
- **avoid glucose and galactose** in diet
- provide child with nutrients via other methods
28
How many dietary amino acids are there ?
20
29
What % of amino acids are absorbed as tri/dipeptides ?
50%
30
Which transporter is used in the absorption of tri/dipeptides in the intestines ?
PepT1
31
What happens to tri/dipeptides once they’re absorbed into the cell from the intestine ?
**hydrolysed into amino acids**, so leave into blood as amino acids
32
What method of transport does the PepT1 transporter use ?
**co transport** / secondary active transport
*(uses a H gradient rather than Na)*
33
What would cause amino acids in the urine ?
rare genetic diseases that affect protein transporters, resulting in **malabsorption**
34
Which enzyme mainly influences lipid digestion ?
Pancreatic lipase
*some gastric lipase has a minor role*
35
What substance is the digestion of lipids dependant on ?
bile salts
36
Are bile salts acids or alkali ?
Acids
37
What are the roles of bile salts in lipid digestion ?
1. **emulsify** large fat droplets *= increases SA for action of lipase*
2. **transport via** formation of mixed **micelles** *= stabilises products of triglyceride hydrolysis*
38
What do micelles contain ?
- bile salts
- monoglycerides
- fatty acids
- phospholipids
- cholesterol
39
What is the condition caused primarily by an absence/deficiency of bile salts ?
**Steatorrhea** (a fatty type of diarrhoea)
40
Currently, what are the proposed methods of lipid transport across membranes ?
**simple diffusion**
*phospholipids in micelles bind to the phospholipid membrane and release contents into the cell*
**Free fatty acid transporters**
*FAT and CD36*
**Monoglyceride transporters**
*evidence for carrier-mediated mechanisms (no details)*
41
What is the average dissociation constant (pKa) of free fatty acids ?
~ 4.9
*means: at pH 4.9, 50% of fatty acids will be undissociated and susceptible to simple diffusion*
42
Describe how lipids are turned into chylomicrons …
- bile salts emulsify + form micelles
- micelles diffuse into cells
- triglycerides reform within cell
- packaged into chylomicrons in endoplasmic reticulum
43
Where are chylomicrons transported to ?
Lymphatic system via lacteals
44
Where is cholesterol absorbed?
duodenum
45
Which protein is cholesterol absorption dependant on ?
NPC1L1 protein
*Niemann-Pick C1-Like 1 protein*
46
What does the NPC1L1 protein do in the intestine ?
**enables receptor mediated endocytosis** of cholesterol into the cells
47
Which receptor is the target of the drug Ezetimibe ?
NPC1L1 protein
48
What is the action of the drug Ezetimibe ?
Inhibits endocytosis of cholesterol into intestine = **decreases plasma cholesterol**
49
What drug can Ezetimibe be used in combo with/instead of ?
statins
*usually in cases where the patient is allergic to statins*
50
Name 3 short chain fatty acids …
- butyrate
- propionate
- acetate
51
Where do short chain fatty acids present in the GI tract come from ?
**Bacterial fermentation** of undigested polysaccharides in the colon
*not really from the diet*
52
What are short chain fatty acids mainly used for once absorbed ?
intracellular metabolism
*don’t pass into the blood at all really*
53
How are short chain fatty acids absorbed ?
by the **SMCT1 protein** = a **Na-coupled transporter**
*driven by a Na-K pump on opposite membrane*
54
Which short chain fatty acid is associated with a **decreased risk** of colon cancer and metabolic diseases (e.g diabetes) ?
butyrate
55
Which short chain fatty acids are associated with an **increased risk** of colon cancer and metabolic diseases (e.g diabetes) ?
proprionate
acetate
56
How is water absorbed into the small intestine ?
**following an osmotic gradient**
*full explanation unknown…
- via junctional complexed between cells ?
- via SGLT1 and amino acid transporters ?
- NOT aquaporins*
57
What creates the osmotic gradient across the intestinal epithelium ?
absorption of nutrients
*water follows*
58
What volume of water is absorbed per day, on average, by:
a) small intestine?
b) colon ?
8.4L total
a) small intestine = 6.5 L
b) colon = 1.9 L
59
Where is the majority of water absorbed in the GI tract?
**small intestine** *following nutrient absorption*
60
Roughly how much water is lost in faeces each day ?
100 ml
61
Which 2 ions come out in quite significant amounts in faeces ?
potassium (90mM)
bicarbonate (30mM)
62
Which steroid hormone regulates sodium channels in the distal colon?
aldosterone
= increases sodium absorption
63
What effect does aldosterone have on sodium absorption in the distal colon ?
INCREASES absorption
64
Is the transport/absorption of Na throughout the GI tract classed as active or passive transport ?
active
65
Is the transport/absorption of bicarbonate throughout the GI tract classed as active or passive transport ?
passive
66
Why do people with severe/chronic diarrhoea get hypokalaemia and metabolic acidosis ?
because a lot of **potassium and bicarbonate are lost in faeces** anyway, so excessive **diarrhoea will expel excessive quantities of both** ions resulting in hypokalaemia and metabolic acidosis
67
What causes diarrhoeas ?
increased osmotic load in the colon = increased fluid in faeces
68
What makes up the increased osmotic load in the colon of patients with diarrhoea ?
incomplete digestion and absorption of food
*due to:
- lack of enzymes
- lack of transporters
- excess ion secretion into gut
- damage to mucosal cells*
69
What can cause a person to have a lack of digestive enzymes or absorption transporters ?
**congenital problems **
- lactase deficiency
- glucose-galactose malabsorption (SGLT1 mutation)
**disease of pancreas and biliary systems = steatorrhoea**
- pancreatitis
- cystic fibrosis
- hepatitis
- gall stones
70
What can cause damage to the mucosa in the GI tract ?
**immune/autoimmune diseases**
- coeliac
- crohn’s
**bacterial infections**
= damage epithelium and decrease SA
71
What does dysentery mean ?
dysentery = an infection of the intestines that causes **diarrhoea containing blood or mucus**
72
What are the main infection causes of diarrhoea in the UK ?
Rotavirus
Norovirus
73
How does cholera and rotavirus cause diarrhoea ?
- virus produces a toxin
- toxin hijacks normal cellular processes
- *intestine normal secretes 1L water a day*
- *in cholera* secretion of water exceeds 20L a day
- toxins also may inhibit Na absorption (but not SGLT1)
74
What is oral rehydration therapy? How does it help in cases of cholera causing diarrhoea ?
oral rehydration therapy **= drinking water with salt and glucose in it**
helps because toxins from cholera inhibit Na absorption but not SGLT1 (glucose) absorption, so this **increases glucose absorption, taking water with it**
75
What are the 2 distinct groups of vitamins ?
1. fat soluble
2. water soluble
76
Name the fat soluble vitamins …
- Vitamin **A**
- Vitamin **D**
- Vitamin **E**
- Vitamin **K**
77
Name the water soluble vitamins …
- Vitamins in the **B** group
- Vitamin **C**
78
How are fat soluble vitamins absorbed ?
**facilitated diffusion** and/or **endocytosis**
79
What type of digestion/absorption also helps with absorption of fat soluble vitamins ?
requires optimal **fat digestion**
80
Patients with which diseases will be more likely to have fat-soluble vitamin deficiencies ?
- pancreatic disease
- biliary disease
81
How are water soluble vitamins absorbed ?
specific transporters (**facilitated and secondary active**)
*B12 is via endocytosis*
82
What are the 2 routes of Ca absorption ?
- **transcellular** = through the cell via transport proteins
- **paracellular** = through tight junctions between the cells
83
Which vitamin regulates the transcellular route of Ca absorption ?
Vitamin **D**
84
What is the name of the Ca channel protein in…
a) the small intestine ?
b) the kidney ?
small intestine = **TRPV6**
kidney = **TRVP5**
85
In the process of Ca absorption in the small intestine, which protein does Ca bind to within the epithelial cell?
Calbindin
86
Why does Ca bind to a protein within the epithelial cells ?
- **removes excess Ca from cytoplasm** *because high levels of free Ca is detrimental to the health of the cell*
- enables **movement of Ca** from apical to basolateral membrane
87
How is Ca removed from the intestinal epithelium in absorption ?
**active transport** via **PMCA** pump
- Ca out, H+ in
88
How does Vitamin D regulate Ca absorption ?
vitamin D **binds to receptors that trigger transcription** of 3 proteins:
- TRPV6 (Ca channel protein)
- Calbindin
- PMCA (Ca-H pump)
89
Where does iron absorption occur in the GI tract ?
duodenum
90
Is iron absorption a transcellular or paracellular process ?
transcellular
*(travels through the cell, rather than between them)*
91
Is iron absorption a transcellular or paracellular process?
transcellular
*(travels through the cell, rather than between them)*
92
What are the 2 mechanisms in which iron enters the apical membrane in the duodenum ?
- via **DMT protein** (co-transports Fe and H+)
- in the form of **heme** (not certain how)
93
In the process of iron absorption in the duodenum, what happens to heme once inside the cell ?
heme is **oxidised, releasing** iron in form of **ferric ions**
94
What form of iron is released from heme in the absorption of iron in the duodenum ?
ferric ions
95
What substance is reduced to form ferris ions ?
ferric ions —> ferrous ions
96
In the absorption of iron in the duodenum, what happens to the remaining heme protein once ferric ions have been released ?
It goes to form **biliverdin, and therefore bilirubin**
*biliverdin is the precursor to bilirubin*
97
What is the precursor of bilirubin?
biliverdin
98
In the absorption of iron in the duodenum, what happens to the ferrous ions within the cell ?
they are bound to a protein called **mobilferrin**, as they are toxic when left free
99
What is the ionic formulae for
a) ferric ions ?
b) ferrous ions ?
ferric ions = Fe3+
ferrous ions = Fe2+
100
What is the name of the protein that ferrous ions bind to once inside the intestinal epithelium ?
mobilferrin
101
How does iron leave the cell via the basolateral membrane ?
facilitated diffusion via FP1protein
102
What is the name of the iron transport protein on the basolateral membrane of the duodenal epithelial cells ?
FP1 protein
*(ferroportin 1)*
103
What is the iron plasma-transport protein called ?
plasma transferrin
104
Which hormone regulates iron absorption ?
Hepcidin
105
Where is hepcidin produced ?
by liver cells
106
Which transporter protein does hepcidin bind to in the regulation of iron absorption in the duodenum ?
FP1
*ferroportin 1* on basolateral membrane
107
What causes a decrease in hepcidin production ?
iron deficiency
*hepcidin is produced when the body has surplus iron in the blood*
