Physiology of Nutrient Digestion & Absorption Flashcards
1
Q
What is digestion?
A
enzymatic conversion of complex dietary substances to a form that can be absorbed.
2
Q
What is luminal digestion?
A
Mediated by pancreatic enzymes secreted into the duodenum.
3
Q
What is membrane digestion?
A
Mediated by enzymes situated at the brush border of epithelial cells.
4
Q
What is absorption?
A
The processes by which the absorbable products of digestion are transferred across both the apical & basolateral membranes of enterocytes.
5
Q
What are enterocytes?
A
Absorptive cells of the intestinal epithelium.
6
Q
What is the overall process of digestion & absorption called?
A
Assimilation
7
Q
What percentage of total energy requirement do digestive carbohydrates provide?
A
~45%
8
Q
What percentage of total energy requirement do polysaccharides (polymers of glucose) provide?
A
45-60%
9
Q
What are the two types of polymers of glucose?
A
Starch (plant) & glycogen (animal)
10
Q
What are the two types of starch (plants)?
A
Amylose & amylopectin
11
Q
What type of chain is amylose & what are the linkages?
A
Straight, α-1,4 linkages
12
Q
What type of chain is amylopectin & what are the linkages?
A
Branched, α-1,4 & α-1,6 linkages
13
Q
What type of branch is glycogen & what are the linkages?
A
Branched (more highly branched than amylopectin), α-1,4 & α-1,6 linkages
14
Q
What percentage of total energy requirement do oligosaccharides provide?
A
30-40%
15
Q
What are the two types of oligosaccharides?
A
Sucrose (table sugar) & lactose (milk sugar)
16
Q
What is sucrose made up of & what are the linkages?
A
Glucose + fructose, α-1,2 linkages
17
Q
what is lactose made up of & what are the linkages?
A
Glucose + galactose, β-1,4 linkages
18
Q
What percentage of total energy requirements do monosaccharides provide?
A
5-10%
19
Q
What are the two types of monosaccharides?
A
Glucose & fructose
20
Q
What must happen to all dietary carbohydrates before absorption?
A
Must be converted to monosaccharides
21
Q
What is the role of α-amylase?
A
An endo-enzyme, breaks down linear internal α-1,4 linkages but not terminal α-1,4 linkages. Hence, no production of glucose
22
Q
What linkages can α-amylase not cleave?
A
α1,6 linkages at branch points in amylopectin or α-1,4 linkages adjacent to branch points.
23
Q
What kind of products are made by the action of α-amylase?
A
linear glucose oligomers (maltotriose, maltose) & α-limit dextrins.
24
Q
What are oligosaccharidases?
A
Integral membrane proteins with a catalytic domain that faces the lumen of the GI tract
25
What is the role of lactase?
Has only one substrate - breaks down lactose to glucose & galactose
26
What do all the other oligosaccharidases cleave?
Terminal α-1,4 linkages of maltose, maltotriose, & α-limit dextrins
27
What can maltase degrade?
α-1,4 linkages in straight chains oligomers up to 9 monomers in length
28
What is sucrase specifically responsible for?
Hydrolysing sucrose to glucose & fructose
29
How is isomaltase unique?
The only enzyme that can split the branching α-1,6 linkages of α-limit dextrins
30
How fast are the hydrolysis reactions performed by maltase, isomaltase, sucrase, & lactase?
Maltase, sucrase, & isomaltase - occur at faster rate than subsequent transport of the released monomers. Lactase - rate of hydrolysis is rate limiting in assimilation
31
Where does the absorption of the final products of carbohydrate digestion: Glucose, Galactose and Fructose occur?
Duodenum & jejunum
32
What kind of process is the absorption of the final products of carbohydrate digestion?
2 step process - involves entry & exit from enterocytes via the apical & basolateral membranes respectively.
33
What are glucose, galactose, & fructose absorbed by?
Glucose & galactose - Secondary active transport mediated by SGLT1
Fructose - facilitated diffusion mediated by GLUT5
34
What are the exit for all monosaccharides mediated by?
Facilitated diffusion by GLUT2
35
In secondary transport for final products of carbohydrate digestion, what must the substrate be?
i) A hexose in D-conformation ii) one that can form a pyranose ring
36
Describe the mode of operation of SGLT1
1. 2 Na+ binds: 2. Affinity for glucose increases, glucose binds: 3. Na+ and glucose translocate from extracellular to intracellular: 4. 2 Na+ dissociate, affinity for glucose falls: 5. Glucose dissociates: 6. Cycle is repeated
37
What must protein be digested into for an efficient absorption?
Oligopeptides & amino acids - 4 major pathways
38
What does protein assimilation account for in daily energy intake?
10-15% (less in developing countries)
39
Describe digestion in the stomach
HCl begins to denature proteins
Pepsin cleaves proteins into peptides
40
What is the optimum pH of pepsin?
1.8-3.5, inactivated at alkaline pH
41
What is pepsin?
Endopeptidase with preference for bonds between aromatic & larger neutral amino acids. Not essential for protein digestion
42
Describe digestion in duodenum
The five pancreatic proteases are secreted as proenzymes from the acinar cells of the exocrine pancreas and converted to active form in the duodenum. They function as either endopeptidases, or exopeptidases.
43
State the name of the pancreatic enzymes, their action, & their products
Trypsin, endopeptidase, oligopeptides (2-6 amino acids)
Chymotrypsin, endopeptidase, oligopeptides (2-6 amino acids)
Elastase, endopeptidase, oligopeptides (2-6 amino acids)
Carboxypeptidase A, exopeptidase, single amino acids
Carboxypeptidase B, exopeptidase, single amino acids
44
How much of protein is converted to oligopeptides and free amino acids by pancreatic proteases?
70% to oligopeptides & 30% to free amino acids
45
Where are additional proteases present?
At the brush border
Within the cytoplasm of the enterocyte
46
Why are brush border peptidases numerous in number?
Because each enzyme attacks a limited number of peptide bonds and the oligopeptides to be digested are extremely varied in their structure (up to 24 different amino acids are present in protein)
47
What do brush border peptidases have affinity for?
Larger oligopeptides (3-8 amino acids)
48
What kind of peptidases can brush border peptidases be?
Endopeptidases or exopeptidases - the latter comprising both aminopeptidases & carboxypeptidases
49
What are cytoplasmic peptidases?
Less numerous than brush border peptidases
Primarily hydrolyse dipeptides or tripeptides
50
What are the different mechanisms in brush border amino acid absorption?
At lease 7 different mechanisms:
5 are Na+-dependent co-transporters mediating ‘uphill’ movement (secondary active transport) eg system B0AT1 (SLCA19) – mediates uptake of neutral amino acids (dysfunction results in Hartnup disease)
2 are Na+ independent eg system b0+AT (SLC7A9/SCL3A1 dimer) – mediates uptake of cationic amino acids (dysfunction results in cystinuria)
51
What are the different mechanisms in basolateral membrane amino acid absorption?
At least 5 different mechanisms: 3 mediate efflux of amino acids and are Na+-independent: 2 mediate influx (supplying the enterocyte’s nutritional requirements along with absorbed amino acids) and are Na+-dependent – net movement is thus bidirectional
52
How are Di-, tri-, and tetra-peptides absorped?
Via H+-dependent mechanism (PepT1, SLC15A) at brush border (co-transport):
further hydrolysed to amino acids within the enterocyte
Na+-independent systems at the basolateral membrane (facilitated transport)
53
54
How much of the daily energy requirement do ingested lipids provide?
55-60%
55
What do ingested lipids comprise of?
Fats/oils - triacylglycerols (TAGs) - 90% of total - typically long chain fatty acyl esters of glycerol. Fatty acids may be saturated or unsaturated - ratio is high in animal fats, low in plant fats
Phospholipids [mostly glycerophospholipids eg phosphatidylcholine (lecithin)]
Cholesterol & cholesterol esters
Fatty acids may
56
Are ingested lipids soluble in water?
Are either insoluble (eg cholesterol esters, TAGs), or poorly soluble in water causing special problems for digestion & absorption
57
What must solid fat & oil masses be converted into?
An emulsion of small oil droplets suspended in water
58
How does emulsification occur?
Mouth - chewing
Stomach - gastric churning & squirting through the narrow pylorus. Content mixed with digestive enzymes from mouth & stomach
Small intestine - segmentation & peristalsis mix the luminal content with pancreatic & biliary secretions
59
What do droplets produced by mechanical disruption provide?
Vast increase in the surface area to volume ratio that increases the area of the oil-water interface at which digestion by lipases & other Esterases can accomplish digestion
60
How are droplets stabilized?
By the addition of a ‘coat’ of amphiphilic molecules that form a surface layer on the droplets.
61
What do the amphiphilic molecules that form a surface layer on the droplets include?
Certain products of lipid digestion itself (eg fatty acids, monoacylglycerols)
Biliary phospholipids
Cholesterol
Bile salts (when the droplets have progressively been reduced to unilamellar & mixed micelles)
62
What is lingual phase in lipid digestion of TAG by lipases?
Mouth - quantitatively unimportant in humans
63
What is gastric phase in lipid digestion of TAG by lipases?
Stomach - by gastric lipase (& lingual lipase in saliva) modest importance in adults (in the absence of pancreatic insufficiency), more so in infants
64
What is gastric lipase secreted in response to?
Gastric from chief cells
65
What is the pH of gastric lipase? What is it resistant to? When is it inactive? What does it hydrolyse?
pH= 4, resistant to pepsin
Inactive in the duodenum due to digestion by pancreatic protease protease & unfavourable pH
Preferentially hydrolyses TAGs at the 3 position
66
What do the products diacylglycerol + free fatty acid hydrolysed from TAGs by gastric lipase + H2O stimulate?
CCK release from duodenum & secretion of pancreatic lipase
67
What type of fatty chains are absorbed by the stomach?
Short & medium chain fatty acids, long chain fatty acids are not
68
What does digestion by pancreatic lipases produce?
2-monoacylglycerol & free fatty acids
69
What is the intestinal phase in digestion of pancreatic lipase?
Duodenum - by pancreatic (TAG) lipase - main lipid digestive enzyme in adults
70
Where is pancreatic lipase secreted and from what response is it secreted?
Acinar cells in pancreas in response to CCK which also stimulate bile flow
71
What does the full activity of pancreatic lipase require?
Colipase cofactor
Alkaline pH
Calcium
Bile salts
Fatty acids
72
What does pancreatic lipase mainly hydrolyse?
TAGs at the 1 & 3 positions
73
What are the additional lipases?
Carboxyl ester hydrolase
Phospholipase A2
74
What is the role of bile salts?
Bile salts released from the duodenum in bile from gall bladder in response to CCK act as detergents to help emulsify large lipid droplets to small droplets
Amphipathic
Increase surface area for attack by pancreatic lipase, but block access of the enzyme to the TAGs
75
What does failure of bile salts secretion result in?
Lipid malabsorption - steatorrhoea (fat in faeces)
Secondary vitamin deficiency due to failure to absorb fat soluble vitamins (A,D,E & K)
76
What is the role of colipase?
An amphipathic polypeptide secreted with lipase by the pancreas - binds to bile salts & lipase allowing access by the latter to tri- & di-acylglycerols
77
How is colipase secreted?
Secreted as inactive procolipase which is activated by trypsin
78
What happens to the final products of lipid digestion?
Stored in, & released from, mixed micelles.
As TAGs towards the surface of the emulsion droplets are hydrolysed, they’re replaced by TAGs within the core, decreasing droplet size until mixed micelles results
79
Where do free fatty acids & monoacylglycerols transfer?
Between mixed micelles & the apical membrane of enterocytes.
80
How do free fatty acids & monoacylglycerols enter the cell?
By passive diffusion &/or membrane fatty-acid translocases, fatty-acid binding proteins & fatty-acid transport proteins.
81
What is the transport of short chain (i.e. 6 carbon) and medium (i.e. 8-12 carbon ) fatty acids?
Diffuse through the enterocyte, exit through the basolateral membrane & enter the villus capillaries
82
What is the transport of long chain fatty (i.e. 12 carbon) fatty acids and monoglycerides?
Resynthesized to triglycerides in the endoplasmic reticulum & are subsequently incorporated into chylomicrons
83
How is cholesterol absorbed?
Transport by endocytosis in clatherin coated pits by Niemann-Pick C1-like 1 (NPC1L1) protein
84
What is the function of ezetimibe & what is it used in?
Binds to NPC1L1, prevents internalization, & thus cholesterol absorption. Used in conjunction with statins in hypercholesterolaemia
85
How does absorption of calcium occur?
By passive (i.e. paracellular; whole length of small intestine) and active (i.e. transcellular; mainly duodenum and upper jejunum) transport mechanisms
86
What happens when the concentration of calcium in chyme is below 5mM?
Absorption is mainly active
87
What regulates active calcium absorption?
1,25-dihydroxyvitamin D3 (calcitriol) and parathyroid hormone (increases 1,25-dihydroxyvitamin D3 synthesis)
88
What increases the expression of calcium channel (TRPV6) & Calcium-ATPase (PMCA1)?
1,25-dihydroxyvitamin D3
89
What is the role of iron?
An important constituent of haemoglobin & myoglobin & acts as co-factor for numerous enzyme-mediated processes. Crucially important in carriage of oxygen by haemoglobin.
90
How much iron is there in the body?
Approximately 3-5g of iron, mostly (~2/3rds) within haemoglobin
91
What is the regulation of iron in the body?
Daily loss of iron from the body (via urine, sweat & desquamated enterocytes) is an unregulated process.
Iron balance within the body, long-term, depends upon tightly regulated absorption of iron across the duodenum which matches losses.
92
What is dietary iron?
Mainly in the oxidised form, Fe3+, present in meat, or vegetables, as:
* inorganic iron
* haem (which is most easily absorbed)
* ferratin (an iron store)
93
What is the daily amount required for dietary iron?
Only in minor amounts: 12-15mg ingested - but only 5-10% absorbed; female more than male
94
What does iron deficiency cause?
Microcytic anaemia: world wide health problem particularly in women of childbearing age
95
Why is iron excess toxic?
Due to accumulation in liver, pancreas & heart & molecularly the production of hydroxyl radicals & hydroxide ions
96
What does Fe2+ bind to in the stomach?
Gastroferrin
97
How does reduction of Fe3+ to Fe2+ occur?
By Fe3+ accepting an electron
98
What promotes Fe3+ accepting an electron?
HCl within the stomach
Vitamin C
A ferric reductase, duodenal
cytochrome B (Dctyb),
present on the brush border
membrane of enterocytes
Gasteroferrin, secreted by
gastric parietal cells,
reversibly binds Fe2+
preventing the formation of
insoluble anion salts
99
How is Fe2+ influx via DMT1 (Fe2+ transport coupled to H+ transport) succeeded?
By transport by mobilferrin to ferroportin 1 that mediates efflux
100
What happens to some Fe2+ in the cytoplasm?
Combine with cytoplasmic apoferratin & is stored (oxidised to Fe3+) as ferratin
101
What happens to haem entering the cytoplasm by an uncertain mechanism?
Degraded by haem oxidase to release Fe2+ that may be stored, or exported. Biliverdin is also produced
102
What increases the expression of divalent metal transporter 1?
Blood loss
103
What decreases the expression of divalent metal transporter 1?
human haemochromatosis protein (HFE) – mutations of HFE cause hereditary haemochromatosis (iron levels build up over the years), due to iron accumulation
104
How is ferroportin 1 regulated?
Negatively regulated by the hormone hepicidin.
105
When is hepicidin released & what is its role?
Released from liver when body iron levels are high. Major control on iron absorption
106
What is the function of hephaestin?
Oxidises Fe2+
107
How much of vitamin B12 (cobalamin) is present in the diet?
Present in minutes amounts in the diet (5-15 micrograms day - daily requirement approximately 6 micrograms per day, hence efficient & selective absorption required)
108
Where is vitamin B12 not present in?
Vegetables - vegans susceptible to deficiency
109
What does absorption of fat soluble vitamins (ie A - retinoic acid, D, E, & K) require?
Absorption requires adequate bile secretion and an intact intestinal mucosa - incorporated into mixed micelles
110
How are fat vitamin soluble transported?
Usually passively transported into enterocytes - incorporated into chylomicrons, or VLDLs
111
What distributes fat soluble vitamins?
Intestinal lymphatics
112
How are water soluble vitamins (ie B complex vitamins - but not B12, C, H) transported?
Transport processes in the apical membrane are similar to those described for monosaccharides, amino acids and di- and tri-peptides. May be either Na+-dependent, or Na+-independent.
113
How is vitamin B9 (folic acid) transported?
the Na+-independent proton-coupled folate transporter 1; FOLT – aka SLC19A1) – driven by pH gradient?
114
How is vitamin C (ascorbate) transported?
the Na+-dependent vitamin C transporters (SVCT1 and 2, aka SLC23A1 and SLC23A2) – couples inward movement of 2 Na+ to 1 ascorbate
115
How is vitamin H (biotin) transported?
the Na+-dependent multivitamin transporter (SMVT, aka SLC5A6) – couples inward movement of 2 Na+ to one biotin
