DIGESTION AND ABSORPTION

DIGESTION BEGINS IN THE ORAL CAVITY

- Saliva
o Secreted by salivary glands
o Consists of about 99.5% water
o Acts as lubricant for mastication and for swallowing
o Vehicle for excretion of
 Certain drugs (ethanol and morphine),
 Inorganic ions (K+, Ca2+, HCO3)
 Thiocyanate
 Iodine
 IgA
o pH: usually about 6.8
- Mastication subdivides the food, increasing its solubility and surface area for enzyme atta
- Saliva contains an amylase
o Salivary amylase
 Capable of bringing about the hydrolysis of starch and glycogen to maltose
 Readily inactivated at pH 4.0 or less
o Lingual lipase
 Secreted by dorsal surface of tongue (Ebner’s glands)
 In rat, it is the only preduodenal lipase

PROTEIN DIGESTION BEGINS IN THE SMOTACH

- Gastric secretion is known as gastric juice

o Clear, pale yellow fluid
o O.2 – 0.5% HCl
o pH about 1.0
o 97-99% water
 Remainder consists of mucin and inorganic salts, digestive enzymes (pepsin and rennin), and lipase
- Hydrochloric acid denatures protein and kills bacteria
o Parietal (oxyntic) cells
 Source of gastric HCl
 Process is similar to that of “chloride shift” described for RBC
 Also resemblance to renal tubular mechanisms for secretion of H+
 Wherein the source of H+ is also the carbonic anhydrase catalyzed formation of H2CO3 from H20 and CO2
 Secretion of H+ into the lumen is an active process driven by membrane-located H+ -K+ ATPase
o Ouabain-insensitive
- Pepsin initiates protein digestion
o Pepsin
 Produced in the chief cells as inactive zymogen, pepsinogen
 Activated to pepsin by H+ (splits off a protective polypeptide to expose active pepsin)
 And also pepsin itself (further activates molecules of pepsinogen: autocatalysis)
 Splits denatured protein into large polypeptide derivative
 An endopeptidase
 Since it hydrolyzes peptide bonds within nthemain polypeptide structure rather than adjacent to amino or carboxyl
terminal residues (being an exopeptidase)
 Specific for peptide bonds formed by aromatic amino acids or dicarboxylic amino acids (glutamate)
- Rennin (Chymosin, Rennet) coagulates milk
o Important in infants because it prevents rapid passage of milk from the stomach
o In the presence of calcium, rennin changes the casein of milk irreversibly to paracasein
 Then acted on by pepsin
o Absent from the stomach of adults
o Used in making of cheese (rennet)
- Lipases continue the digestion of tracylglycerols
o Gastric lipase
 Secreted by stomach
o Lingual and gastric lipases initiate lipid digestion by hydrolyzing triacylglycerols containing short-, medium, and unsaturated long-chain fatty
acids, to form
 Free fatty acid
 1,2 diacylglycerols
 Sn-3 ester bond being the primary site of hydrolysis
o Enzymes are destroyed at low pH
o Active after feeding because of buffering action of dietary proteins in stomach
o Ph optimum: 3 – 6
o Preduodenal lipase
 Important during neonatal period when pancreatic lipase may be low in activity and milk fat need to be digested
 Retention time: 2 – 4 hours in stomach
 Milk fat act as good substrate for this enzyme
 Because it contains shirt and medium chain fatty acids, tend to be esterified in the sn-3 position
o Short and medium chain fatty acids
 Absorbed via stomach wall and enter portal vein
 o Longer chain fatty acid
 Pass on to the duodenum

DIGESTION CONTINUES IN THE INTESTINE

- Stomach concents (chyme) are introduced during digestion into the duodenum through pyloric valve
- Alkaline content of pancreatic and biliary secretion neutralizes acid of chime and changes the pH to alkaline side
o This shift necessary for the activity of the enzymes containe in pancreatic and intestinal juice but it inhibits further action of pepsin
- Bile emulsifies, neutralizes, and excretes cholesterol and bile pigments
o Composition of bile
o Properties of bile
 Emulsification
 Bile salt has ability to lower surface tension
 Enable them to emulsify fatsand dissolve fatty acids and water-insoluble soaps
 Present of bile in intestine is important to accomplish digestion and absorption of fats as well as absorption of fat-soluble
vitamins A, D, E, K
 Neutralization of acid
 Bile
o pH slightly above 7
o Neutralizes acid chime from the stomach and prepares it for digestion in the intestine
 Excretion
 Bile is important vehicle for bile acid, and cholesterol excretion
 Also removes many drugs, toxin, bile pigments, and inorganic substances (Cu, Zinc, Hg)
o Pancreatic secretion contains enzymes for attacking all the major foodstuffs
 Pancreatic secretion is a nonviscid watery fluid
 Contains some proteins and organic and inorganinc compounds
o Na+, K+, HCO3, and Cl
o Ca2+, Zn2+, HPO4, SO4 – in small amounts
 pH is distinctly alkaline
o 7.5-8.0 or higher
 Trypsin, chymotrypsin, and elastase are endopeptidase
 Trypsin
o Specific for peptide bonds of basic amino acids
 Chymotrypsin
o Specific for peptide bonds containing uncharged amino acid residues such as aromatic amino acids
 Elastase
o Has broad specificity in attacking bonds next to small amino acids residues such as glycine, alanine, serine
 ALL THREE ENZYMES ARE SECRETED AS ZYMOGEN
 Enterokinase
o Activates tyrpsinogen
o Secreted by intestinal mucosa
o Hydrolyzes a lysine peptide bond in the zymogen releasing small polypeptide that allows molecule to unfold as
active trypsin
 Once tryspsin is formed, it will attack other zymogens in pancreatic secretion such as
 Chymotrypsinogen  chymotrypsin
 Proelastase  elastase
 Procarboxypeptidase  carboxypeptidase
 Carboxypeptidase is an exopeptidase
 Attacks the carboxyl terminal peptide bond, liberating single amino acids
o Amylse attacks starch and glycogen
 Pancreatic α-amylase
 Starch-splitting action of pancreatic function is due to this enzyme
 Similar in action to salivary amylase, hydrolyzing starch and glycogen to
o Maltose
o Maltotriose (three α-glucose residues linked by α14 bonds)
o Mixture of branched oligosaccharids
o Nonbranched oligosaccharides and some glucose
o Lipae attackes the primary ester link of triacylglycerols
 Pancreatic lipase
 Acts at the oil-water interface of finely emulsified lipid droplets
o Formed by mechanical agitation in the gut in presence of products of
 Lingual and gastric lipase activity
 Facilitates hydrolysis of pancreatic lipase, particularly in milk triacylglycerol
 Bile salts
 Colipase
 Protein present in pancreatic secretion
 Function Is to overcome bile salt inhibition by
o Binding in a 1:1 molar ration with lipase
o Binding to bile salt-covered traicylglycerol interface
 Anchors lipase to its triacylglycerol substrate

 Phospholipase A2
 Also present in pancreatic secretion)
 Secreted in proforms and require activation by tryptic hydrolysis of specific peptide
bonds
  Secreted in proforms and require activation by tryptic hydrolysis of specific peptide
bonds
 Phospholipids
 Ca2+ is necessary in their activity
 Inhibited by bile salts
 Specific for hydrolysis of primary ester linkages, at positions 1 and 3 of triacylglycerols
 2nd and 3rd fatty acids are hydrolyzed from triacylglycerol with difficulty by this enzyme
o Digestion proceeds by removal of terminal fatty acids to produce 2-monoacylglycerol
o Reuires isomerization to a primary ester linkage to achieve complete hydrolysis
o Relatively slow process
o 2-monoacylglycerol are major end product
 Enetrostatin
 A pentapeptide that acts as a satiety signal for lipids
 Bile salt- activated lipase
 Present in human milk ester
 An added factor for ensuring complete digestion of milk fat when it comes into contact with bile salts in duodenum
 Important in premature infants
 Identical to a pancreatic bile salt-activate lipase
o Cholesteryl esters are broken down by a specific hydrolase
 By cholesteryl hydrolase (cholesterol esterase)
o Ribonuclease (RNAse) and deoxyribonuclease (DNase)
 Responsilble for digestion of dietary nucleic acids
o Phospholipase A2, hydrloyzes the ester bond in the 2 position of glycerophospholipids
 Both biliary and dietary origins to form lysophospholipids
 Being deterdents, aid emulsification and digestion of lipids
- Intestinal secretion complete the digestive process
o Intestinal juice secretd by glands of Brunner and Lieberkuhn contains digestive enzymes, includes:
 Aminopeptidase
 An exopeptidase
 Attacking peptide bonds next to amino terminal amino acids of polypeptides and oligopeptides
 Dipeptidase
o Complete digestion of dipeptides to free amino acids
 Disaccharidases and oligosaccharidases
 α-glucosidase (maltase)
o removes single glucose residues from α(14)- linked oligosacchardies and disaccharidesm, starting from the
nonreducing ends
 sucrose-isomaltase complex
o found as the proenzyme on one polypeptide chain by as active enzymes on separate polypeptides chain but as
active enzymes on separate polypeptides chain
o hydrolyzes sucrose and 16 bonds in α-limit dextrins
 β-glucosidase (lactase)
o Removes galactose from lactose
o Which also attacks cellobiose and other β-glycosides
o Has a second catalytic site that splits glycosylceramides
 Trehalase
o For hydrolyzing trehalose
o Remain attached to brush border of enterocyte while the catalytic domains are free in the lumen to react with
substrate
 Phosphatase
 Removes phosphate from certain organic phosphates such as hexose phosphates, glycerophosphate, and nucleotides
derived from diet and digestion of nucleic acids by nucleases
 Polynucleotidases
 Which split nucleic acids into nucleotides
 Nucleosidases (nucleoside phosphorylases)
 Catalyze phosphorolysis of nucleosides to give free nitrogen base plus a pentose phosphate
 Phospholipase
 Attack phospholipids to produce glycerol, fatty acids, phosphoric acid, and bases such as choline
o The major products of digestion are assimilated
 Products of digestion
 Carbohydrates  monsaccharides (glucose)
 Proteins  amino acids
 Triacylglycerol  fatty acids, glycerol, monoacylglycerol
 Nucleic acid  nucelobases, nucleosides, an pentoses
 Dietary fiber
 Make up the bulk of the residues from digestion

ABSORPTION FROM THE GASTROINTESTINAL TRACT RESULTS IN PASSAGE OF NUTRIENTS INTO THE HEPATIC PORTAL VEIN OR THE LYMPHATICS

- Small intestine
o Main absorptive organ
o About 90% of ingested food and water are absorbed
- 2 pathways for the transport of materials absorbed by the intestine
o Hepatic portal system
 Which leads directly to the liver and transporting water-soluble nutrients
o Lymphatic vessels
 Which lead to the blood by way of thoracic duct and transport lipid-soluble nutrients
 - Carbohydrates are absorbed as monosaccharides
o Absorbed from jejunum into blood of portal venous system in the form of monosaccharides chiefly as
 Hexose (glucose, fructose, mannose, and galactose)
 Pentose sugars (ribose)
o 2 mechanism are responsible for the absorption of monosaccharides
 Active transport
 Molecular configurations that seem necessary for active transport , which are present in glucose and galactose
o OH on carbon 2
o Pyranose ring
o Methyl or substituted methyl group on carbon 5
 Simple diffusion
 Fructose is transported by this mechanism
o By means of a sodium-independent facilitative transporter (GLUT)
o Glucose facilitates fructose absorption
- Active absorption of glucose is powered by the sodium pump
o Sodium-dependent glucose transporter (SLGT 1) binds glucose and Na+
 Transport them both through plasma membrane of intestinal cell
o Active transport of glucose in inhibited by ouabain (a cardiac glycoside)
 An inhibitor of sodium pump
o Phlorhizin
 Known inhibitor of glucose reabsorption in the kidneytubule
o Hydrolysis of lactose proceeds at only half the rate for sucrose accounting that digestion of lactose does not lead to saturation of transport
mechanism for glucose and galactose
- The products of lipid digestion are absorbed from bile salt micelles
o Bile salts pass on the ileum, where most are absorbed into the enterohepatic circulation by an active process
o Phospholipids of dietary and biliary origin
 Hydrolyzed by phospholipase A2 of pancretice secretion to factty acids and lysophospholipids
 Are also absorbed form the micelles
o Cholesteryl esters are hydrolyzed by cholesteryl ester hydrolase of pancreatice juice,
o Over 98% of dietary lipid is normally absorbed
o 1-monoacylglycerols are further bydrolyzed to produce free glycerol and fatty acids by an intestinal lipase (glycerol esterhydrolase)
o 2-monoacylglycerols are reconverted to triacylglycerols via monoacylglycerol pathway
- The products of protein digestion are absorbed as individual amino acids
o Natural (L) isomer of amino acid is actively transported across intestine from mucosa to serosa
 Vitamin B6 (pyridoxal phosphate) may be involved in this transfer
 2,4-dinitrophenol inhibits transport
 Can be transported by Na+-dependent mechanism
 A neutral amino acid carrier
o Phenylalanine carrier
o Methionine carrier
o A carrier specific for imino acids such as prline and hydroxyproline
- Bacteria in the large intestine cause putrefaction and fermentation
o During putrefaction and fermentation, bacteria produce various gases
 CO2, methane, hydrogen, nitrogen, hydrogen sulfide,
 Acetic, lactic, propionic, butyric acid
o Bacterial decomposition of phosphatidylcholine may produce choline and related toxic amines such as neurine
o Many amino acids undergo decarboxylaion as a result of action of intestinal bacteria to produce toxic amines (ptomaines)
o Such decarboxylation reactions produce
 Cadaverine from lysine
 Agmatine from arginine
 Tyramine from tyrosine
 Putrescine from ornithine
 Histamine form histidine
 Indole and methylindole (skatole: responsible for odor of feces) from Tryptophan
o Oral administration of neomycin reduce quantity of ammonia delivered from intestine to blood
- Site of absorption of nutrients
o Jejunum
 Glucose, other monosaccharides, some disaccharides, monoacylglycerol,glycerol, cholesterol, FA, amino acids, peptides, vitamins,
folate, electrolytes, iron, calcium, water
o Ileum
 Bile acids, vitamin B12, electrolytes, and water
- Intestinal bacteria are also beneficial
o Intestinal flora make up 25% of dry weight of feces

CLINICAL ASPECTS

- The limited solubility of cholesterol in bile causes gallstones

- Defects in enzymes of carbohydrate digestion cause specific disorders
o Lactose intolerance
 Deficient in lactase enyme
 Three types of lactase deficiency
 Inherited lactase deficiency
o Rare
o Symptoms of intolerance develop very soon after birth
 Secondary low-lactase activity
o Examples are tropicsl and nontropical (celiacl)sprue, kwashiorkor, colitis, gastroenteritis, after surgery for
peptic ulcer
  Primary low-lactase activity
o Common syndrome
o Gradual decline in activity of lactase
o Not due to lack of lactase mRNA
o Sucrose deficiency
 Together with isomaltase
o Disacchariduria
 Increase in excretion of disaccharides due to disaccharidase deficiency
 300 mg are excreted in urine
o Monosaccharide malabsorption
 Congenital condition due to single mutation in which glucose and galactose are absorbed only slowly
 Defect in Na+ glucose cotransporter carrier mechanism
 Fructose in normal, not absorbed by this transporter
- In chyluria, chylomicrons are present in urine
o Chyluria
 Abnormality which patient excretes milky urine
 Because of presence of an abnormal connection between urinary tract an dlymphatic drainage system of intestine
 So called chylous fistula
 Feeding triacylglycerol with medium chain length result in disappearance of chyluria
o Chylothorax
 Abnormal connection between pleural space and lymphatic drainage of small intestine
 Result in accumulation of milky pleural fluid
 Feeding triacylglycerol with short-chain length result in disappearance of chylothorax
o Colipase deficiency
 Patients suffer form steatorrhoea as a result of defective pancreatic lipase activity
- Absorption of undigested polypeptides may cause antigenic reactions
- Summary of disturbances due to malaborption
o Sign or symptoms Substance malabsorbed
 Anemia Iron, vitamin B12, folate
 Edema Products of protein digestion
 Tetany Calcium, magnesium, vitamin D
 Osteoporosis Calcium, products of protein digestion, vitamin D
 Milk intolerance Lactose
 Bleeding, bruising Vitamin K
 Steatorrhea (fatty stools) Lipids and fat-soluble vitamins
 Hartnup disease Neutral amino acids

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