Small intestine and pancreas Flashcards
1
Q
Where is secretin released?
A
Secreted by S cells in duodenum
2
Q
What is the action of secretin?
A
- Causes secretion of bicarbonate to buffer pH of chyme entering SI
- Triggers insulin release
- Regulates secretion in stoamch, pancreas and liver
3
Q
Under what circumstances is secretin released?
A
Stimulated by HCl
4
Q
Where is cholecystokinin released from?
A
I cells in mucosal epithelium of small intestine (secreted into duodenum)
5
Q
Under what circumstances is cholecystokinin released?
A
Stimulated by HCl, amino acids and fatty acids
6
Q
What is the action of cholecystokinin?
A
Stimulates release of digestive enzymes from pancreas and bile from gall bladder
7
Q
Where is gastric inhibitory polypeptide released from?
A
Synthesised by K cells in small intestine
8
Q
Under what circumstances is gastric inhibitory polypeptide released?
A
Stimulated by hyperosmolarity of glucose in duodenum
9
Q
What is the action of gastric inhibitory polypeptide?
A
- Inhibits HCl secretion in stomach
- Inihibits gastric motility by inhibiting secretion of acid and pepsin
- Induces insulin secretion from pancreas
10
Q
What are the 3 theories of appetite regulation in common domesticated species?
A
- Glucostat
- CCK
- Lipostat
11
Q
Briefly outline the glucostat theory of appetite regulation
A
- Involves glucose, VFAs, AAss
- high levels of these cause satiety centre to be activated
- Inhibit appetite centre
- Reduce feeding behaviour
12
Q
Briefly outline lipostat theory of appetite regulation
A
- Fat deposits and leptin
- Fat deposits trigger leptin release and activate satiety centre
13
Q
What duodenal factors inhibit stomach emptying?
A
- Secretin
- Gastric inhibitory polypeptide (GIP)
- Cholecystokinin (CCK)
14
Q
Describe the intestinal phase of digestion in the duodenum
A
- pH of stomach low, duodenum fragile
- When pH in duodenum too low, triggers release of secretin
- Triggers release of bicarbonate from pancreas
- Contraction of gall bladder controlled by CCK
- Sensitive to fat, bile reeased by gall bladder
- Reduces size of fat blobs coming out of stomach
- Enzymes used to digest protein
15
Q
What is the effect of bicarbonate releas from the pancreas to the duodenum?
A
- Increases pH to stop acid damaging duodenum
- Creates environment stomach enzymes and proenzymes cannot survive in
- Blocks overall digestion process
16
Q
Describe the intestinal phase of digestion in the large intestine
A
- Digestion carries on
- Movement occurs slowly - 4 types of contraction
- Segmentatino, peristalsis, antiperisalsis and mass movement
- Mass movement driven by stretch of wall
- Stomach and duodenum promote large intestine contraction via long reflex mesenteric nervous syste (Gastro-colic reflex)
17
Q
What are the polysaccharides in starch?
A
- Amylose
- Amylopectin
18
Q
Describe amylose
A
- Linear structure
- alpha-1-4-linkage
- Cabrons 1-4 are linked
- Ppolar
- H bonds between monomers hold it in spiral shape
19
Q
Describe amylopectin
A
- Branched chains
- Alpha 1-6 linkage
- Starch molecules
20
Q
What does the structure of amylopectinmean for starch?
A
Starch molecules clustered in granules and are insoluble in water
21
Q
Describe glycogen
A
- Glucose store in animals
- Made up of single highly branched polysaccharide
- Has both alpha 1-4 and alpha 1-6 linkages
- Usually more branched than amylopectin
- More water soluble, increased branching means water can get trapped in spaces
- Stored as granules in liver and skeletal muscle
22
Q
What is the action of alpha-amylase on polysaccharides?
A
- Break bonds between monosaccharides
- Hydrolysis
- Substitutes bond for water molecule
- Preferentially breaks alpha-1-6-linkages
23
Q
Desscribe glucose digestion and absorption in the small intestine
A
- In mouth, salivary apha-amylase begins starch digestion to maltose, some glucose and dextrins
- Complete in small intestine by pancreatic enzymes
- Luminal phase then membranous phase to complete digestion
24
Q
Describe the luminal phase of carbohydrate digestion in the small intestine
A
- Starch breakdown started by alpha-amylase completed by pancreatic amylase to maltose
- Cannot yet be absorbed
25
Describe the membranous phase of carbohydate digestion in the small intestine
- Disaccharides to monosaccharides by glucosidase enzymes (maltase, sucrase, lactase)
- Known as brush border enzymes as are located here
- Resulting monosaccharides transported across intestinal lumen
26
How are glucose and galactose absorbed in the small intestine?
Actively
27
How is fructose absorbed in the small intestine?
Facilitate transport
28
What is the absorption of glucose limited by?
The rate of epithelial transport only
29
What is the rate of lactose digestion limited by?
Rate of hydrolysis
30
Describe cellulose
- Non-starch polysaccharide
- beta 1-4 linkages
- Structural role, major component of plant cell wall
- Polysaccharide of glucose
- No branching
- Insoluble in water, indigestible in humans
31
Describe the locationof the pancreas
- Adjacent to stomach and duodenum
| - One lobe lies within duodenal flexure
32
List the products released by the endocrine function of the pancreas
- Glucagon
- Insulin
- Somatostatin
33
What cell type secretes glucagon?
Alpha cells
34
What cell type secretes insulin?
Beta cells
35
What cell type secretes somatostatin?
Delta cells
36
What cell type secretes digestive enzymes?
Cells of the pancreatic acini
37
What is produced by the exocrine function of the pancreas?
Digestive enzymes
38
Where are the digestive enzymes produced in the pancreas?
Pancreatic acini
39
What cells are in the Islets of Langerhans?
- Alpha, beta, delta
40
List the enzymes produced by the exocrine pancreas
- Trypsin
- Chymotrypsin
- (Pro)elastase
- Pro-carboxypeptidase
- Lipase
- Phospholipase
- Amylase
- Ribonuclease
- Deoxyribonuclease
41
What are the functions of trypsin, chymotrypsin and (pro)elastase?
- Act on proteins and peptides
- Cleave interior peptide bonds
- Are endonucleases
42
What is the functin of pro-carboxypeptidase?
- Acts on peptides/proteins
- Releases amino acid at carboxy terminal
- Exopeptidase
43
What is the function of lipase?
- Acts on triglycerides
| - Cleaves ester bond at 1&3 positions yeilding free fatty acids and monoglycerides
44
What is the function of phospholipase?
- Acts on phospholipids
| - Cleaves ester bond at 2- position of phospholipids
45
What is the function of amylase?
- Acts on starch (polysaccharides)
| - Cleaves to maltose
46
What is the function of ribonuclease?
- Acts on RNA
| - Cleaves RNA to nucleotides
47
What is the function of deoxyribonuclease?
- Acts on DNA
| - Cleaves DNA to nucleotides
48
Define "zymogen" and give examples
Inactive nezyme precursor
| - Trypsinogen, chymotrypsinogen, pepsinogen, proelastase, procarboxypeptidase
49
Define exopeptidase
Detach terinal acids from polypeptides e.g. aminopeptidases (on membrane of small intestine only) or carboxypeptidases
50
Define endopeptidase
Hydrolyse internal peptide bonds of a protein (e.g. typsin, chymotrypsin, pepsin, elastase)
51
Define protease
An enzyme that conducts proteolysis i.e. begins protein catabolism by hydrolysis of the peptide bonds between adjacent amino acids in polypeptide chain
52
Name the groups of proteases
- Serine proteases (trypsin, chymotrypsiin)
- Threonine proteases
- Cysteine proteases
- Aspartic acid proteases
- Metallo proteases
- Glutamic acid proteases
53
Describe the mechanism of action of serine endopeptidases
- Synthesised by pancreatic acinar cells
- Secreted into SI
- Share similar structure, differ in peptide bond they cleave
- Highly specific to regions of polypeptide chain, based on side chains of amino acid residues surrounding site of cleavage
54
What bonds are cleaved by chymotrypsin?
- Bonds following large hydrophobic amino acid residues
| - e.g. on C-terminal side of phenylalanine, tryptophan and tyrosine residue
55
What bonds are cleaved by trypsin?
- Bonds after positively-charged amino acid residue
| - e.g. C-terminal side of arginine and lysine residue
56
What bonds are cleaved by elastase?
- Bonds after small neutral amino acid residue
| - e.g. alanine, glycine and valine (connective tissues in meat)
57
What is an aminopeptidase?
An exopeptidase that attacks amino terminal (N-terminal) of peptides secreted from small intestine
58
What are the 2 main pathways of protein absorption?
- Peptide transport
| - Single amino acid transport
59
Describe the peptide transporter
- High afinity for di-tripeptides
- Prefers peptides with L-amino acids and is driven by electrochemical gradient produced by Na+ pump
- Represents majority of peptide transport i.e. few enter as single amino acids
60
Describe the amino acid transporter
- From intestinal lumen is an active process
- Involves Na+ dependent, carrier mediated cotransport system similar to that for glucose
- Selective carrier systems for certain groups of amino acids
- Some sharing of transporters
61
What are the 4 groups of amino acids within which transporters are shared?
- Neutral amino acids (neutral brush border system)
- Acidic (dicarboxylic) amino acids
- Imino amino acids (glycine, proline and hydroxyproline)
- Basic amino acids
62
Define exocrine
- "out of the body" into gut
| - Ducts to get where needs to be
63
Define endocrine
- Into the body (tissues)
| - No ducts
64
Name the major components of bile
- Polar derivatives of cholesterol
- Lecithin
- Bile pigments (bilirubin)
- Bila salts and bile acids
65
What are bile acids and where are they formed?
- Polar derivatives of cholesterol
- Amphipathic molecules with detergent like properties, emulsion
- Formed in liver, secreted into gall bladder
66
Describe the breakdown of triacylglycerols by lipases
- CCK stimulates bile secretion into intestine, aid digestion of fats and fat-soluble vitamins
- Bile acids start emulsion process
- Phospholipase A2 (pancreas) transforms lecithin (bile) into lysophospholipid that acts as a strong detergent
- Large drop of fat covered by components of bile to form emulsion
- Lingual lipase first then pancreatic lipase
- Pancreatic lipase secreted from pancreas as proenzyme activated by trypsin
- Catalyse hydrolysis of TAGs at positions 1 an 3, forming 1,2-diacylglycerols and then 2 monoacylglycerols
- Colipase aids binding of enzyme at lipid-water interface
67
Why is the majority of lipid taken up as monoacylglycerol?
- Lipase removes 2 fatty acids per TAG
| - Ratio of 2:1 monoacylglycerols to cleaved TAG, so 70% lipid taken up as MAG
68
Outline the basics of lipid absorption by intestinal cells
- micells needed for lipid to be able to enter cells
- Concentration gradient aids passive absorption into enterocyte
- Intracellular fatty-acid binding protein maintains this gradient
- Fat components accumulate inside ER of epithelial cells
- TAG molecules reformed
- Chol transformed into cholesterase
69
Describe chylomicrons
- TAG and cholsterol esters carried in core
- Outer skin of chylomicrons made up partly of amphipathic phospholipids, partly of free cholesterol, partly of protein
- Cholesterol esterified to increase hydrophobicity
- TAGs/lipids/FAs/chol/cholesterols gather in ER to form chylomicrons (lipoproteins)
70
What are the different of lipoprotein?
- Chylomicron
- Very low density lipoprotein
- Intermediate density lipoprotein
- Low density lipoprotein
- High density lipoprotein
71
What is the major protein in chylomicrons?
Apolipoprotein B
72
What is the function of apolipoprotein B in chylomicrons?
- Forms hydrophilic shell around lipid layer and allows it to form a stable structure in the blood
- Activates lipoprotein lipase
73
How do lipoproteins get around the body?
- use lymphatic circulation cia thoracic duct
- Too big to enter systemic circulation via capillaries
- Bypass hepatic metabolism
74
What is the function of lipoprotein lipase?
- Enzyme attached to lumenal surface of small blood vessels
| - Catalyses hydrolytic cleavage of fatty acids from TAGs of chylomicron
75
What happens the the fatty acids and monoacylglycerols released from chylomicrons?
Picked up by body cells for use as energy sources
76
Describe chylomicrons in terms of density
Largest, lowest in density
- High lipid/protein ration
- Highest % weight of TAG
77
Describe VLDLs in terms of density
Very low density lipoprotein
| - 2nd highest in TAG as % weight
78
What does IDL stand for?
Intermediate density lipoprotein
79
Describe LDLs in terms of density
- low density lipoprotein
| - Highest in cholesteryl esters as % of weight
80
Describe HDLs in terms of density
- High density lipoproteins
| - Highest in density due to high protein/lipid ratio
81
What is meant by Michaelis-Menton kinetics?
- At low substrate concentrations the substrate is rate limitigng - 1st order kinetics (kinetics reduces over time as substrate is used up)
- At high substrate concentration the enzyme is at maximal capacity - zero order kinetics
82
What is Vmax?
The macimum rate of the reaction at the maximum substrate concentration
83
What is Km?
The rate constant
- Measure of enzyme-substrate complex stability
- Indicator of enzyme affinity for substrate
84
What is the importance of Km?
- Describes the enzyme affinity for substate
- Concentrations fo susbtrates in cells should be approx. the Km
- Used in lab assays to get results in correct range
- Depends on precise relationship between substrate and enzyme
85
Why should the concentration of substrates in cells be close to the Km?
Allows good physiological regulation
86
What is shown by a low Km?
High affinity
87
What is shown by a high Km?
Low affinity
88
What are the main types of enzyme inhibitors?
- Competitive vs non-competitive
- Irreversible vs reversible
- Competitive reversible
- Non-competitive
- Irreversible
89
Descrieb the basics of a competitive reversible enzyme inhibitor
- Mimics substrate or transition state analogue
- Substance competes with substrate for active site
- Negative feedback signal sent to turn off production or release of susbtrate
- Not transformed into a product
- Reversible
- Amount of inhibition depends on Ki
- Increases Vm, no change in Vmax
90
What is a transition state analogue?
- Enzyme and substrate combined together
| - Enzyme-substrate complex
91
What is meant by Ki?
- Enzyme affinity for inhibitor
| - Enzyme may bind preferentially to inhibitor over substrate
92
Describe non-competitive inhibition
- Substrate and inhibitor bind at different site
- Little to no resembalnce to substrate
- Able to bind to enzyme even if E already bound to substrate
- Causes change in 3D structure
- Decreases Vmac, no effect on Km (no change to substrate concentration)
- End product design to bind to allosteric site when high concentrations present to stop production of product, prevent accumulation
93
Describe irreversible inhibition
- Forms covalent bond to amino acid near/at active site
- Permanently inactivates enzyme
- Susceptible AA residues e.g. -OH, -SH (ser, cys)
94
Define the term enzyme
Proteins that function by accelerating chemical reactions in biological systems
95
List the key features of enzyme action
- Higher reaction rates
- Milder conditions required
- Greater reaction specificity
- Capacity for regulation - allostery, covalent modification
96
Explain how enzyme specificity is produced
- Small cleft on surface
- Often non-polar
- Binds complementary substrate
- Highly conserved (same sacross families and species)
- Specific due to shape
- 2 models of substrate binding - lock and key and induced fit
- Depends on specific spatial arrangement of amino acids/atoms
- Able to distinguish stero-isomer
97
Describe the lock and key mechanism of enzyme-substrate binding
Substrate fits exactly into the active site
98
Describe the induced fit mechanism of enzyme-substrate binding
- Enzyme fits around the substrate
- substrate binding induces conformation change in enzyme
- optimal orietation for formation of transition state
- Stabilisation of transition state
- Exlusion of water
99
Define activation energy
The energy required to make a reaction happen
| - Is lowered by enzymes
100
Define specific activity
The way in which an enzyme will only act on one or two substrate
101
List the steps involved in enzyme catalysis
- Stabolose transition state
- Alter substrate orientation
- Change substrate reactivity
- Induce substrate strain
- Exclude water
102
Describe the enzymes function in controlling substrate orientation in enzyme catalysis
- Hold substrate together correctly to allow reaction to take place
- Lines things up to allow interaction
103
Describe the enzyme's role in changing substrate reactivity in enzymes catalysis
- Take susbtrate with slightly wrong ionic charge, temporarily give correct ionic charge and allow substrate to become reactive
- Can be done by acid base catalysis (removal/addition of protins - donor/acceptor in active site)
- Also by covalent catalysis - nucelophilic/electrophilic substitution, reactive amino acids and cofactors
104
Explain why substrate strain is induced in enzyme catalysis
- Expose correct part of substrate
| - Allows that part to tak epart in reaction
105
Explain why water is excluded in enzyme catalysis
Allows reaction to tak eplace without interference
106
Describe the histological appearance of the duodenum
- Villi loonger
| - Submucosa expanded due to presence of Brunner's glands
107
Describe the histological features of the ileum
- Lymph tissue (Peyer's patches) present
| - Short villi
108
Describe the histological appearance of the jejunum
- Shorter villi
| - Thinner submucosa than duodenum
109
Describe the histological appearance of the pancreas
- Glands present
- Lobules and conective tissue septa = looks similar to salivary glands
- Islets's of Langerhans present
- Secretory acini present
- Islets are paler than acini (but look quite similar)
