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1- physiology of nutrient digestion & absorption Flashcards

1
Q

what is digestion?

A

enzymatic conversion of complex dietary substances to form that can be absorbed

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2
Q

what is apical membrane?

A

membrane surface that faces lumen (inner space) of cavity or tube →in small intestine apical membrane faces intestinal lumen

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3
Q

what is secondary active transport?

A

mechanism where movement of 1 molecule across a membrane is coupled with movement of another molecule (often utilises energy stored in conc gradient of 1 molecule to transport another molecule against it’s conc gradient)

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4
Q

what are the names of the 2 main phases of digestion that occur in small intestine?

A
  1. luminal digestion
  2. membrane digestion
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5
Q

what is luminal digestion?

A

breakdown of food in lumen of intestine mediated by pancreatic enzymes secreted into the duodenum

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6
Q

what is membrane digestion?

A

further breakdown of nutrients at brush border of epithelial cells lining the intestine mediated by enzymes situated at the brush border of epithelial cells

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7
Q

what is absorption in intestine?

A

the processes by which the absorbable products of digestion are taken up from intestinal lumen into bloodstream →they’re transferred across both the apical (luminal facing) and basolateral (blood-facing) membranes of enterocytes = they move through transport mechanisms like secondary active transport, facilitated or simple diffusion

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8
Q

what is assimilation?

A

digestion and absorption

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9
Q

what junctions are between enterocytes?

A

tight junctions

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10
Q

what are enterocytes?

A

absorptive cells of the intestinal epithelium

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11
Q

how is glucose digested and absorbed? (what is route)

A

glucose has no digestion and simply diffuses across lumen and epithelium into interstitial space

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12
Q

how are proteins digested and absorbed?

A

proteins are digested by luminal hydrolysis of polymer to monomer, broken down into amino acids that then directly diffuse across lumen,epithelium into interstitial space

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13
Q

how is sucrose digested and absorbed?

A

sucrose is digested by brush border hydrolysis of oligomer to monomers glucose + fructose that can diffuse across lumen, epithelium, interstitial space

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14
Q

how are peptides digested and absorbed?

A

peptides are digested as they move by intracellular hydrolysis and arrive in interstitial space as amino acids

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15
Q

how are triglycerols digested and absorbed?

A

digested by luminal hydrolysis making glycerol + fatty acids that diffuse across lumen, epithelium and then undergo intracellular resynthesis so back as triacylglycerol in interstitial space

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16
Q

what are polymers of glucose?

A

polysaccharides (starch or glycogen)

*starch is again subdivided into amylose + amylopectin

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17
Q

what are oligosaccharides?

A

sucrose + lactose + maltose

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18
Q

what are monosaccharides?

A

glucose + fructose + galactose

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19
Q

what form are carbs absorbed?

A

monosaccharides

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20
Q

what is sequence of carbohydrate digestion from e.g. starch?

A

alpha amylase (produced from salivary and pancreatic glands) catalyses intraluminal hydrolysis to break starch into oligosaccharides (sucrose +lactose+α-limit dextrins)
the oligosaccharides then undergo membrane digestion at brush border catalysed by oligosaccharidases (lactase, maltase, sucrase-isomaltase) to form monosaccharides (glucose, fructose, galactose) that are absorbed

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21
Q

what are examples of oligosaccharidases and what is function?

A

they catalyse membrane digestion at brush border of oligosaccharides to monosaccharides
examples = lactase, maltase, sucrase-isomaltase

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22
Q

is carbs always consumed as big polysaccharides like starch?

A

no can get lactose or sucrose and glucose or fructose from diet = they need less digestion

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23
Q

what is role of alpha amylase?

A

catalyses intraluminal hydrolysis (polysaccharide to oligosaccharide)

= it’s an endoenzyme that breaks down linear internal alpha 1-4 linkages but not terminal alpha 1-4 linkages (hence no production of
glucose - why need another step of cleaving) and producing linear glucose oligomers

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24
Q

what is endoenzyme?

A

(enzyme that catalyses reactions within interior of substrate molecule

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25
Q

what is role of oligosaccharidases?

A
  • Lactase has only one substrate – breaks down lactose to glucose and galactose
  • All other oligosaccharidases cleave the terminal α-1,4 linkages of maltose, maltotriose and α-limit dextrins (to make glucose)
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26
Q

what is the unique function of isomaltase?

A

(type of oligosaccharidase)
- it is only enzyme that can split the branching alpha 1-6 linkages of alpha-limit dextrins

= so if α-limit dextrins formed, only isomaltase can be used to break down

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27
Q

what is sucrase specifically responsible for?

A

sucrase is example of oligosaccharidases

  • specifically responsible for hydrolysing sucrose to glucose and fructose
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28
Q

what is the faster step in digestion of carbs
1. hydrolysis reaction performed by maltase, sucrase + isomaltase
2. subsequent step that is transport of released monosaccharides across the intestinal epithelium into the bloodstream

are there any exceptions to this?

A

step 1 is faster

yes - hydrolysis of lactose by lactase proceeds slower than the transport (so step 2 faster in this scenario) = this means lactase is limiting factor in assimilation of lactose-derived sugars

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29
Q

what is rate limiting factor for assimilation of lactose-derived sugars?

A

lactase (hydrolysis of lactose by lactase takes longest)

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30
Q

where in GI tractdoes absorption of monosaccharides occur?

A

in duodenum or jejunum

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31
Q

what is the 2 step process of absorption?

A

entry and exit from the enterocytes via the apical and basolateral membranes, respectively

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32
Q

for entry: how are glucose and galactose absorbed? (what transporter + type etc)

A

by secondary active transport mediated by SGLT1

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33
Q

for entry: how is fructose absorbed (what transporter + type)?

A

by facilitated diffusion mediated by GLUT5.

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34
Q

how are all monosaccharides absorbed to exit enterocytes?

A

Exit for all monosaccharides is mediated by facilitated diffusion by GLUT2

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35
Q

what is mode of operation for SGLT1?

A

SGLT1 is the transporter for entry of glucose + galactose into enterocyte that works by secondary active transport so coupled protein

  1. 2 Na+ binds
  2. affinity for glucose increases so glucose binds
  3. Na+ and glucose translocate from extracellular to intracellular
  4. 2 Na+ dissociate, affinity for glucose falls and glucose also dissociates
  5. cycle repeated
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36
Q

what must happen to protein?

A

be digested to oligopeptides and amino acids for efficient absorption – four major pathways exist

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37
Q

what are the types of protein digestion?

A
  1. luminal digestion by gastric + pancreatic enzymes
  2. brush border enzymes
  3. intracellular digestion
38
Q

what is the luminal digestion by gastric + pancreatic enzymes type of protein digestion?

A

initially broken down by gastric enzymes (primarily pepsin) into peptides then in lumen of small intestine broken down by trypsin, chymotrypsin into small amino acids

39
Q

what is the brush border enzymes type of protein digestion?

A

luminal enzymes break down to peptides and then brush border enzymes break into amino acids

40
Q

what are the 3 different types of peptidases that hydrolyse proteins?

A

aminopeptidases, carboxypeptidases, endopeptidases

41
Q

what effect does gastric acid have on proteins?

A

changes tertiary structure of protein (denature)

*this happens in stomach

42
Q

what is function of pepsin in digestion in stomach?

A
  • works at optimum pH 1.8-3.5
  • endopeptidase with preference for bonds between aromatic and larger neutral amino acids
  • is not essential for protein digestion
43
Q

what is the main example of gastric protease?

A

pepsin

44
Q

what are the 5 pancreatic proteases? and how do they become activated?

A

they are secreted as pro-enzymes from acinar cells (functional cells of exocrine pancreas) and converted into active form in duodenum

  1. trypsin (endopeptidase)
  2. chymotrypsin (endopeptidase)
  3. elastase (endopeptidase)
  4. carboxypeptidase A(endopeptidase)
  5. carboxypeptidase B (exopeptidase)
45
Q

what is the differences in products between endopeptidases and exopeptidases?

A

endopeptidases = oligopeptidases (as cut in middle)
exopeptidases = single amino acids (as cut at end)

46
Q

what % of pancreatic proteases convert protein to oligopeptidides and free amino acids?

A

70% of protein to oligopeptides and 30 % to free amino acids

47
Q

where can proteases be found?

A

pancreas, brush border, within cytoplasm of enterocyte (to break indiv amino acids)

48
Q

are there more brush border peptidases or cytoplasmic peptidases?

A

more brush border peptidases

49
Q

what do cytoplasmic peptidases primarily hydrolyse?

A

dipeptides or tripeptides

50
Q

what are the 7 different mechanisms present at brush border (for absorption of amino acids)?

A

5 are Na+ dependant co-transporters mediating “uphill” movement (secondary active transport)

2 are Na+ independent

51
Q

what is an example system of Na+ dependant co-transporters? (for amino acid absorption)

A

example system B0AT1 (SLCA19) – mediates uptake of neutral amino acids (dysfunction results in Hartnup disease)

52
Q

what is an example system for Na+ independent amino acid absorption?

A

example system b0+AT (SLC7A9/SCL3A1 dimer) – mediates uptake of cationic amino acids (dysfunction results in cystinuria)

53
Q

what are the 5 different mechanisms for amino acid absorption in basolateral membrane?

A

basolateral membrane = facing neighbouring cells

  • 3 mediate efflux of amino acids and are Na+-independent
  • 2 mediate influx (supplying the enterocytes nutritional requirements along with absorbed amino acids) and are Na+-dependent – net movement is thus bidirectional
54
Q

what are di, tri and tetra peptides?

A

oligopeptides = short chains of amino acids which are formed during digestion of proteins

they are taken into enterocytes and as move in broken down to peptides then undergo further hydrolysis to leave as amino acids

55
Q

how are di, tri and tetra peptides absorbed across brush border?

A

via H+ dependant mechanisms at brush border, co-transport e.g. PepT1

56
Q

what happens once di, tri and tetra peptides are absorbed across brush border into enterocyte and how do they leave?

A

they are further hydrolysed and then after intracellular hydrolysis, the amino acids are transported across basolateral membrane of enterocyte into bloodstream by Na+-independent systems (facilitated transport)

57
Q

where do things go when transported across basolateral membrane?

A

the basolateral membrane is from enterocyte to bloodstream

58
Q

what type of diffusion do amino acids do to leave enterocytes?

A

to leave = facilitated diffusion (not co-transport)

59
Q

what are some examples of lipids that you can ingest?

A
  • triacylglycerols (TAGs), phospholipids, cholesterol or fatty acids
  • they’re either insoluble or poorly soluble in water (makes sense as very lipophilic)
60
Q

what must ingested lipids be converted into in the body?

A

Must be converted from solid fat and oil masses into an emulsion of small oil droplets suspended in water

61
Q

how does emulsification occur for ingested lipids in body?

A
  • mouth - chewing
  • stomach - gastric churning and squirting through the narrow pylorus. Content mixed with digestive enzymes from mouth and stomach
  • small intestine – segmentation and peristalsis mix the luminal content with pancreatic and biliary secretions
62
Q

what is the effect of emulsion droplets on surface area?

A

solid fat + oils being turned into smaller droplets of lipid by mechanical disruption vastly increase the surface area to volume ratio so enhances the exposure of lipases and esterases so they can be digested

63
Q

what are emulsion droplets stabilised by?

A

the addition of a ‘coat’ of amphiphilic molecules that form a surface layer on the droplets that includes:
- certain products of lipid digestion itself (e.g. fatty acids, monoacylglycerols)
- biliary phospholipids
- cholesterol
- bile salts (when the droplets have progressively been reduced to unilamellar and mixed micelles)

64
Q

when is gastric lipase secreted and from what?

A

secreted in response to gastrin from chief cells

65
Q

what is function of gastric lipases?

A

they digest for example triacylglycerol (TAG) into diacylglycerol + free fatty acid

  • it has a pH optimum of 4 and is resistant to pepsin
66
Q

why is gastric lipase inactive in duodenum?

A

due to digestion by pancreatic protease and unfavourable pH

67
Q

what position does
a) gastric lipases
b) pancreatic lipases
hydrolyse TAGs? (triacyl glycerase)

A

a) preferentially at the 3 position
b) at the 1 and 3 positions

68
Q

what are examples of lipases?

A
  • gastric lipases
  • pancreatic lipases
  • carboxyl ester hydrolase
  • phospholipase A2
69
Q

what secretes pancreatic lipase?

A

acinar cells of pancreas in response to cholecystokinin (CCK) which also stimulates bile flow

70
Q

what are factors required for full activity of pancreatic lipase?

A
  • colipase co-factor = protein co-factor that enhances activity
  • alkaline pH
  • Ca2+
  • bile salts = aid in emulsification which helps make larger surface area for lipase action
  • fatty acids = act as substrate and help initiate hydrolysis
71
Q

where are bile salts released from?

A

they’re released into duodenum in bile from gall bladder in response to CCK

72
Q

what is function of CCK?

A

Cholecystokinin (CCK) is a peptide hormone produced by cells lining the duodenum and jejunum of the small intestine, specifically the I cells of the mucosa

73
Q

what is general function of bile salts?

A

they are amphipathic and act as detergents that help emulsify large lipid droplets to small droplets

74
Q

what happens if failure to secrete bile salts?

A
  • lipid malabsorption, steatorrheoa (fat in faeces)
  • secondary vitamin deficiency due to failure to absorb fat soluble vitamins (A,D,E,K)
75
Q

how do bile salts help emulsify large lipid droplets to small droplets?

A

they increase surface area for attack by pancreatic lipase (by emulsifying) but block access of enzyme to TAGs
- colipase helps solve this problem as helps lipase reach triacylglycerides

76
Q

what is colipase?

A

co-protein that is an amphipathic polypeptide secreted with lipase by pancreas - it binds to bile salts and lipase allowing lipase to bind to tri and di acylglycerides

  • it is secreted as inactive procolipase which is activated by trypsin
77
Q

how do emulsion droplets decrease ins zie until mixed micelle?

A

as TAGs at the surface of emulsion droplets are hydrolysed, they are replaced by tags within the core eventually getting smaller and smaller until mixed micelle

78
Q

how are lipids absorbed from mixed micelles?

A
  1. they’re transferred across apical membrane into enterocytes (they enter by passive diffusion) and/or membrane fatty-acid translocases (fatty acid binding protein & fatty-acid transport proteins)
  2. short + medium chain fatty acids diffuse through enterocyte and exit through basolateral membrane, entering villus capillaries. long chain fatty acids + monoglycerides are resynthesized to triglycerides in ER and incorporated into chylomicrons
79
Q

how are chylomicrons formed?

A

within the enterocytes, long chain fatty acids are resynthesised into triglycerides in the endoplasmic reticulum
chylomicrons are then formed as lipid droplets coated with a layer of phospholipids, cholesterol and proteins called apolipoproteins
they chylomicron coated by apolipoprotein is then exocytosed into central lacteal and they’re carried in lymph vessels to systemic circulation (subclavian vein) via thoracic duct

80
Q

how is cholesterol absorbed?

A

mainly due to transport by endocytosis in clatherin coated pits by a protein (NPC1L1)

81
Q

does calcium absorption require a transport protein - when?

A

can be passive (in small intestine) and can be active (duodenum + upper jejunum)

low levels of calcium means active transport is required

82
Q

how is iron absorbed?

A
  • absorbed across apical membrane by transport processes. carried to basolateral membrane by “molecular chaperone” and transported across basolateral membrane, once outside basolateral membrane, Fe2+ converted to Fe3+ and then distributed to tissues via blood
83
Q

what form is iron mostly in? (like ion form)

A

dietery ion mostly in Fe3+ state but can only be absorbed in Fe2+ so have to be converted

*iron supplements are given as Fe2+

84
Q

how can Fe3+ be reduced to Fe2+?

A

by Fe3+ accepting an electron and being promoted by HCl in stomach, vitamin C, ferric reductase + duodenal cytochrome at brush border

85
Q

what role does gasteroferrin have in reducing Fe3+ and Fe2+?

A

gasteroferrin (secreted by gastric parietal cells) reversibly bind Fe2+ preventing formation of insoluble anion salts

86
Q

what is ferratin?

A

storage form of iron in cell
(made from fe2+ and apoferrin)

87
Q

how is vitamin B12 absorbed?

A
  1. vitamin B12 is ingested in food bound to proteins
  2. stomach acid releases vitamin B12 from protein
  3. haptocorin, secreted in saliva binds vitamin B12 once it’s released in stomach
  4. pancreatic proteases digest haptacorin in small intestine (vitamin B12 released again)
  5. vit B12 binds to intrinsic factor in small intestine
  6. vit B12 intrinsic factor complex absorbed in terminal ileum by endocytosis
88
Q

how are fat soluble vitamins like A,D,E,K absorbed?

A

they’re incorporated into mixed micelles and usually passively transported into enterocytes then incorporated into chylomicrons and distributed by intestinal lymphatics

  • their absorption also requires adequate bile secretion and intact intestinal mucosa
89
Q

how are water soluble vitamins like B complex vitamins (NOT B12), C, H?

A

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

90
Q

what transporter is used for vitamin B9 (folic acid)?

A

the Na+independent proton-coupled folate transporter 1; FOLT – aka SLC19A1) – driven by pH gradient

91
Q

what transporter is used for vitamin C (ascorbic acid)?

A

the Na+dependent vitamin C transporters (SVCT1 and 2, aka SLC23A1 and SLC23A2) – couples inward movement of 2 Na+ to 1 ascorbate

92
Q

what transporter is used for vitamin H (biotin)?

A

the Na+dependent multivitamin transporter (SMVT, aka SLC5A6) – couples inward movement of 2 Na+ to one biotin

GI (56 decks)

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