Digestion

• mouth

• intestinal lumen

glycoside hydrolases (glycosidases) —> they hydrolyze glycosidic bonds

• endoglycosidases —> hydrolyze polysaccharides + oligosaccharides

• disaccharidases —> hydrolyze tri- + disaccharides into their rducing sugar components

are usually specific for the structure + configuration of glycosyl residue to be removed as well as for the type of bond to be broken

• glucose, galactose, fructose (monosaccharides) —> are absorbed by cells of small intestine

1. Digestion begins in the mouth

2. further digestion by pancreatic enzymes in small intestine

3. final carbohydrate digestion by enzymes synthesized by intestinal mucosal cells

4. absorption of monosaccharides by intestinal mucosal cells

• plant origin —> starch (amylose + amylopectin)

• animal origin —> glycogen

• 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

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-)

No

• high acidity inactivates salivary a-amylase

when acidic stomach contents reach small intestine —> bicarbonates secreted by pancreas neutralize it —> pancreatic a-amylase continues starch digestion

• 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

• 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)

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)

fructose uptake requires a sodium-independent monosaccharide transporter for its absorption —> GLUT-5

GLUT-2

• a defect in specific disaccharidase activity —> causes passage of undigested carbohydrates into large intestine

  
  

undigested carbohydrates pass into large intestine —> draw water from mucosa into large intestine because they are osmotically active

—> osmotic diarrhea, abdominal cramps, flatulence

• genetic deficiencies of individual disaccharidases —> result in disaccharide intolerance

• intestinal diseases, malnutration, drugs which injure the mucosa of small intestine

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

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

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

• reduced intake of milk

• usage of lactase-treated products

• intake of lactase in pill form prior to eating

hypolactasia

• disease results in intolerance of ingested sucrose

• found in 10% of Inuits of Greenland + Canada

• treatment: dietary restriction of sucrose + enzyme replacement therapy

• 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

• 90% triacylglycerol

• 10% cholesterol, cholesteryl esters, phospholipids, unesterified (free) fatty acids

1. Processing of dietary lipids in stomach

2. Emulsification of dietary lipids in the small intestine

3. Degradation of dietary lipids by pancreatic enzymes

4. Absorption of lipids by intestinal mucosal cells (enterocytes)

5. Resynthesis of TAG and cholesteryl esters

6. secretion of lipids from enterocytes

   
   

stomach

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

• 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

  
  

• 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

• replacement of pancreatic enzymes + supplementation with fat-soluble vitamins

duodenum

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

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

• TAG

• Cholesteryl ester

• Phospholipids

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

pancreatic cholesteryl ester hydrolase (cholesterol esterase)

• produces cholesterol + free fatty acids

at presence of bile salts —> enzyme requires bile salts for optimum activity

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)

• phospholipase A2

• Cholesteryl ester hydrolase (cholesterol esterase)

• lipase

• phospholipase A2

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)

acts on:

• gallbladder —> causes it to contarct and to release bile

• exocrine cells of pancreas —> release of digestive enzymes

decreases gastric motility

• slower release of gastric contents into the small intestine

• free fatty acids

• free cholesterol

• 2-monoacylglycerol

• primary products of lipif digestion —> free FA, free cholesterol, 2-monoacylglycerol

• bile salts

• fat soluble vitamins (A,D,E,K)

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

• 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

short + medium length fatty acids

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

increased lipid in the feces (=steatorrhea)

disturbance in lipid digestion and or absorption

—> this can result from several conditions

• CF (poor digestion)

• shortened bowel (decreased absorption)

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

• capillaries of skeletal muscles + adipose tissue

• heart

• lung

• kidey

• liver

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

• 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

• 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

• 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

• stomach

• pancreas

• small intestine

1. Digestion of proteins by gastric secretion

2. Digestion of proteins by pancreatic enzymes

3. Digestion of oligopeptides by enzymes of small intestine

4. absorption of amino acids + small peptides

stomach

• hydrochloric acid (secreted by parietal cells)

• proenzyme pepsinogen (secreted by chief cells)

• hydrochloric acid

• pepsin

denaturates proteins —> makes them more susceptible to subsequent hydrolysis by proteases

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

• large polypeptides produced by action of pepsin in the stomach are further cleaved to oligopeptides + AA by the pancreatic proteases

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

• cholecystokinin

• secretin

—> both are polypeptide hormones of digestive tract

• deficiency in pancreatic secretion —> due to chronic pancreatitis, cystic fibrosus, surgical removal of pancreas

  
  

• digestion + absorption of proteins is incomplete

• results in abnormal appearance of undigested proteins in feces

aminopeptidase = exopeptidase

• repeatedly cleaves the N-terminal residue from oligopeptides —> produces even smaller peptides + amiino acids

• 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

are not metabolized by liver

are directly sent from liver via blood to muscles

• 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)