What are the principle sites of carbohydrate digestion?
mouth
intestinal lumen
Which enzyme group cataylzes the carbohydrate digestion?
glycoside hydrolases (glycosidases) —> they hydrolyze glycosidic bonds
which glycosidases are the primary enzymes of carbohydrate digestion?
endoglycosidases —> hydrolyze polysaccharides + oligosaccharides
disaccharidases —> hydrolyze tri- + disaccharides into their rducing sugar components
Are glycosidases specific or nonspecific?
are usually specific for the structure + configuration of glycosyl residue to be removed as well as for the type of bond to be broken
what are the final products of carbohydrate digestion?
glucose, galactose, fructose (monosaccharides) —> are absorbed by cells of small intestine
4 basic steps of carbohydrate digestion?
Digestion begins in the mouth
further digestion by pancreatic enzymes in small intestine
final carbohydrate digestion by enzymes synthesized by intestinal mucosal cells
absorption of monosaccharides by intestinal mucosal cells
what are the major diatery polysaccharides?
plant origin —> starch (amylose + amylopectin)
animal origin —> glycogen
what ist the first step of carbohydrate digestion?
during mastification a-amylase acts briefly on dietary starch + glycogen —> hydrolyzes random a(1->4) bonds
branched amylopectin + glycogen also contain a(1->6) bonds —> a-amylase cant hydrolyze this bonds —> digest contains mixture of branched + unbranched oligosaccharides —> are called dextrins
disaccharides also can not be hydrolyzed by a-amylase
Can humans digest cellulose?
No
celullose consist of glucose residues which are bound by b(1->4) bonds
human do NOT produce the enzyme b(1->4) endoglucosidase (only a-)
Does the carbohydrate digestion continue in the stomach?
high acidity inactivates salivary a-amylase
When does the carbohydrate digestion continue? (after stomach)
when acidic stomach contents reach small intestine —> bicarbonates secreted by pancreas neutralize it —> pancreatic a-amylase continues starch digestion
where does the final step of carbohydrate digestion take place + how does it work?
mucosal lining of the upper jejunum
includes action of several disaccharidases —> these enzymes are secreted + remain located within luminal side of the brush border membranes of intestinal mucosal cells
those enzymes cleave disaccharides into monosaccharides
5 examples of disaccharidases?
isomaltase: cleaves a(1->6)bond in isomaltose
maltase: cleaves maltose + maltotriose —> glucose
sucrase: cleaves sucrose —> glucose + fructose
lactase (b-galactosidase: cleaves lactose —> galactose + glucose
trehalase: cleaves trehalose (a 1->1 disaccharide)
how does galactose + glucose absorption work?
galactose + glucose are transported into mucosal cells by active (energy requiring) process —> requires uptake of sodium ions
—> transport protein is sodium-dependent glucose cotransporter 1 (SGLT-1)
how does fructose absorption work?
fructose uptake requires a sodium-independent monosaccharide transporter for its absorption —> GLUT-5
By which transporter are the monosaccharides transported from the intestinal mucosal cells into the portal circularion?
GLUT-2
What is the main problem in abnormal degradation of disaccharides?
a defect in specific disaccharidase activity —> causes passage of undigested carbohydrates into large intestine
What is the consequence of abdnormal degradation of disaccharides?
undigested carbohydrates pass into large intestine —> draw water from mucosa into large intestine because they are osmotically active
—> osmotic diarrhea, abdominal cramps, flatulence
Reasons for digestive enzyme deficiencies?
genetic deficiencies of individual disaccharidases —> result in disaccharide intolerance
intestinal diseases, malnutration, drugs which injure the mucosa of small intestine
Digestive enzyme deficiency in normal individuals - reason + what happens?
in case of severe diarrhea
brush border enzymes are rapidly lost -> temporary enzyme deficienfy
patients should not drink + eat significant amounts of diary products or sucrose —> this could make diarrhea worse
Lactose intolerance - world population?
more than 3/4 of worlds adults are lactose intolerant —> manifested particularly in certain popularions
90% of adults from Africa or Asia are lactose intolerant
—> due to modified inactive enzyme
Lactose intolerance ->age-dependent
there is an age dependent loss of lactase activity —> reduction in the amount of enzyme
—> caused by variations in DNA sequence of a region in chromosome 2 which controls the expression of the gene for lactase
Treatment od lactose intolerance?
reduced intake of milk
usage of lactase-treated products
intake of lactase in pill form prior to eating
which is another term for lactose intolerance?
hypolactasia
Sucrase-isomaltase complex deficiency - consequences of this disease + populations we can find it in + treatment?
disease results in intolerance of ingested sucrose
found in 10% of Inuits of Greenland + Canada
treatment: dietary restriction of sucrose + enzyme replacement therapy
How can we diagnose a specific enzyme deficiency in a patient?
oral tolerance tests with individual disaccharides
measurment of hydrogen gas in breath —> test to determine amount of ingested carbohydrate not absorbed by the body but which is instead metabolized by intetsinal flora
In which form does the average intake of lipids in adults take place?
90% triacylglycerol
10% cholesterol, cholesteryl esters, phospholipids, unesterified (free) fatty acids
What are the 6 general steps of lipid digestion?
Processing of dietary lipids in stomach
Emulsification of dietary lipids in the small intestine
Degradation of dietary lipids by pancreatic enzymes
Absorption of lipids by intestinal mucosal cells (enterocytes)
Resynthesis of TAG and cholesteryl esters
secretion of lipids from enterocytes
Where does the lipid digestion start?
stomach
which 2 enzymes are important in lipid digestion of TAG with short or medium-chain length of fatty acids (<12C)?
1) lipase (lingual lipase)
originates from glands at the back of the tongue
2) gastric lipase
secreted by gastric mucosa
—> both enzymes are acid stable —> pH optimums 4-6
In which people are the 2 enzymes lingual lipase + gastric lipase especially important?
neonats —> for them milk fat is the primary source of energy
individuals with pancreatic insufficiency + people with cystic fibrosis —> gastric + lingual lipase help those people in digestion of lipids even though they suffer from near or complete absence of pancreatic lipase
Cause of Cystic fibrosis (CF)?
autosomal recessive disease
caused by mutations to gene for CF transmembrane cobductance regulator (CFTR) protein —> this protein functions as chloride channel in epithelium
defective of CFTR results in decreased secretion of chloride + increased reabsorption of sodium + water
in pancreas this decreased hydration results in thickened secretion —> pancreatic enzymes are not able to reach the small intestine —> pancreatic insufficiency
Treatment of CF?
replacement of pancreatic enzymes + supplementation with fat-soluble vitamins
where in the body occurs the process of emulsification of dietary lipids?
duodenum
what is the aim of emulsification of dietary lipids?
emulsification increases the surface area of hydrophilic lipid droplets —> digestive enzymes which work at the interface of the droplet + the surrounding aqueous solution can act effectively
emulsification is accomplished by which 2 complementary mechanisms?
1) use of the detergent properties of bile salts
bile salts (made in liver + stored in gallbladder) are derivatives of cholesterol
consist of sterol ring structure + side chain to which a molecule of glycine or taurine is covalentely attached by amid linkage
these emulsifying agents interact with dietery lipid particles + the aqueous duodenal contents —> they stabilize the particles as they become smaller + prevent them from coalescing
2) mechanical mixing due to peristalsis
Which chemical components are enzymatically degraded by pancreatic enzymes?
TAG
Cholesteryl ester
Phospholipids
Which 2 enzymes are involved in the digestion of TAG and what are there functions?
1) Esterase (pancreatic lipase)
removes the fatty acids at carbon 1+ 3 -> primary product of hydrolyzes are a micture of 2-monoacylglycerol + free fatty acids
2) Colipase
also secreted by pancreas
binds lipase at ratio 1:1
anchors in lipid-aqueous interface
they restore the activity of lipase in the presence of inhibitors
which enzyme is involved in cholesteryl ester degradation?
pancreatic cholesteryl ester hydrolase (cholesterol esterase)
produces cholesterol + free fatty acids
When is the cholesteryl ester hydrolase activity greatly increased?
at presence of bile salts —> enzyme requires bile salts for optimum activity
which enzyme is involved in phospholipid degradation?
Phospholipase A2
removes one fatty acid from carbon 2 of phospholipid —> lysophospholipid
remaining fatty acid at C1 can be removed by lysophospholipase —> glycerrylphosphoryl base (may be excreted in feces, further degraded or absorbed)
Which enzymes of lipid digestion require bile salts for optimum activity?
phospholipase A2
Cholesteryl ester hydrolase (cholesterol esterase)
Which enzymes of lipid digestion are activated by trypsin?
lipase
What controls the pancreatic secretion of hydrolytic enzymes?
hormones
cholecystokinin (CCK) —> poduced in cells of mucosa of small intetsine when there is presence of lipids or partially digested proteins entering lower duodenum + jejunum
secretin —> causes pancreas + liver to release solution rich in bicarbonates -> helps neutralize pH of intestinal contents (pH optimum for pancreatic enzymes)
CCK acts on which structures?
acts on:
gallbladder —> causes it to contarct and to release bile
exocrine cells of pancreas —> release of digestive enzymes
does CCK have an impact on gastric motility?
decreases gastric motility
slower release of gastric contents into the small intestine
what are the primary products of lipid digestion in jejunum?
free fatty acids
free cholesterol
2-monoacylglycerol
Which structures together form micelles in the small intetsine?
primary products of lipif digestion —> free FA, free cholesterol, 2-monoacylglycerol
bile salts
fat soluble vitamins (A,D,E,K)
What is the structure of a micelle?
disk shaped cluster of ampiphatic lipids that coalesce with their hydrophobic groups on the inside + their hydrophilic groups on the outside
—> are soluble in aqueos envoíronment of intestinal lumen
How + where are micelles absorbed?
primary site of lipid absorption = brushborder membrane of enterocytes (mucosal cells)
—> this membrane is separated from the liquid contents of intestinal lumen by an unstirred water layer that mixes poorly with bulk fluid
—> hydrophilic surfaces of micelles facilitates the transport of the hydrophobic lipids through the unstirred water layer of brush border membrane —> there they are absorbed
Which lipids do Not require the help of mixed micelles to be absorbed in intestinal mucosa?
short + medium length fatty acids
What happens after mixed micelles are absorbed by the enterocytes?
the mixture of lipids migrates to the endoplasmic reticulum where biosynthesis of complex lipids takes place
—> FA are first converted into their activated form by the enzyme acyl-CoA synthetase (thiokinase)
—> 2-monoacylglycerols are converted into TAG by the enzyme complex TAG synthase
—> Lysophospholipids are recycled to form phosphilipds by acyltransferase
—> cholesterol is esterified to a FA by acylCoA cholesterol acyltransferase
What is the result of Lipid malabsorption?
increased lipid in the feces (=steatorrhea)
What can be the reason for lipid malabsorption?
disturbance in lipid digestion and or absorption
—> this can result from several conditions
CF (poor digestion)
shortened bowel (decreased absorption)
What happens after the resynthesis of TAG + cholesteryl esters?
the newly synthesized TAG + cholesteryl esters are very hydrophobic —> it is necessary that they are packaged as particles of lipid droplets surrounded by a thin layer composed of phospholipids, unesterified cholesterol and a molecule of the characteristics protein apolipoprotein B-48
—> this layer stabilizes the particle + increases its solubilty
TAG contained in chylomicrons is primarly broken down in which tissues?
capillaries of skeletal muscles + adipose tissue
heart
lung
kidey
liver
Which enzyme degrades TAG in cholymicrons into free FA + glycerol?
lipoprotein lipase
enzyme is synthesized by adipocytes + muscle cells
is secreted and becomes associated with luminal surface of endothelial cells of capillary beds of peripheral tissues
What is the FAte of free fatty acids?
free FA derived from hydrolysis of TAG may enter directly adjacent muscle cells or adipocytes or may be transported in blood associated with serum albumin until they are taken up by cells
most cells can oxidize FA to produce energy
adipocytes can also reesterify FA to produce TAG molecules —> are stored until FA are needed by the body
What is the fate of glycerol?
is released from TAG
is almost exclusively used by liver to produce 3-phosphate —> can either enter glycolysis or gluconeogenesis by oxidation to dihydroxyacetone phosphate
What is the fate of the remaining chylomicron components?
after most of TAG has been removed the chylomicron remmants bind to receptors on liver —> are then endocytosed
remants are then hydrolyzed to their component parts —> cholesteryl esters, phospholipids, apolipoproteins, fat soluble vitamins, some TAG
cholesterol + nitrogenous bases of phospholipids can be recycled by body
Which 3 organs produce proteolytic enzymes for the digestion of dietary proteins?
pancreas
small intestine
what are the general 4 steps of protein digestion?
Digestion of proteins by gastric secretion
Digestion of proteins by pancreatic enzymes
Digestion of oligopeptides by enzymes of small intestine
absorption of amino acids + small peptides
where does the digestion of proteins begin?
what does gastric juice contain?
hydrochloric acid (secreted by parietal cells)
proenzyme pepsinogen (secreted by chief cells)
which 2 components are important in the protein digestion in the stomach?
hydrochloric acid
pepsin
what is the function of hydrochloric acid in the digestion of proteins?
denaturates proteins —> makes them more susceptible to subsequent hydrolysis by proteases
What is the function of pepsin in protein digestion?
pepsin = an endopeptidase
proenzyme pepsinogen is activated to pepsin by HCL or atocatalytically by other pepsin molecules that have alraedy been activated
pepsin releases peptides and a few amino acids from dietary proteins
What happenes with dietary proteins that enter the small intestine?
large polypeptides produced by action of pepsin in the stomach are further cleaved to oligopeptides + AA by the pancreatic proteases
What is the specificity of pancreatic enzymes + an example?
each pancreatic enzyme has a different specificity for the amino acid R-groups adjacent ti the susceptible peptide bond
trypsin
it cleaves only when the carbonyl group of the peptide bind is contributed by arginine or lysin
which hormones mediate the release of pancreatic zymogens?
cholecystokinin
secretin
—> both are polypeptide hormones of digestive tract
What is the cause of abnormalities in protein digestion?
deficiency in pancreatic secretion —> due to chronic pancreatitis, cystic fibrosus, surgical removal of pancreas
What may be the result of abnormalities in protein digestion?
digestion + absorption of proteins is incomplete
results in abnormal appearance of undigested proteins in feces
What is the function of the enzyme aminopeptidase?
aminopeptidase = exopeptidase
repeatedly cleaves the N-terminal residue from oligopeptides —> produces even smaller peptides + amiino acids
How does the absorption of free amino acids work?
free AA are talen into enterocytes by Na+-linked secondary transport system of apical membrane
are released into the portal system by facilitated diffusion
AA are either metabolized by the liver or released into the general circulation
What happens with branches-chained AA after their absorption?
are not metabolized by liver
are directly sent from liver via blood to muscles
How does the absorption of small peptides work?
Di- + Tripeptides are taken up by H+-linked transport system
then are hydrolyzed in cytosol to amino acids
AA are released to portal system by facilitated diffusion —> we only can find free AA in portal vein after a meal containing proteins (not peptides)
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