Dr. Nurdin A. Mappewali, Sp. Biok.Department of BiochemistryFaculty of Medicine UNHASBiomedical Science 2Makassar, 3rd March 2011

Introduction General Principles of Digestion Digestive Juices and Enzymes Digestion and Absorption of Carbohydrates Digestion and Absorption of Lipids Protein Digestion and Amino Acid Absorption Liver and Bilirubin Metabolism

Digestion:Mechanical digestion: breaking food in small particles so they are easily broken down by enzymes mouth and stomachChemical digestion: pancreas and duodenum

Nutrient absorption: small intestine

Water reabsorption: colon

Koolman, 2004

The process of digestion is characterized by several specific stagesInteraction of fluid, pH, emulsifying agents, and enzymes

This requires concerted actions of the salivary glands, pancrease, gall bladder, and liver

Lubrications and homogenizationsSecretion of enzymesSecretion of electrolytes, hydrogen ion, and bicarbonateSecretion of the bile acidsFurther hydrolysis of the oligomers and dimers Specific transport of digested material

Major function of the gastrointestinal organs in digestion and absorption

OrganPrimary functionSalivary glandsProduction of fluid and digestive enzymes for homogenization, lubrication, and digestion of carbohydrate (amylase) and lipid (lingual lipase)StomachSecretion of HCl and proteases to initiate hydrolysis of proteinsPancreaseSecretion of HCO3-, proteases, lipases, and amylase to continue digestion of protein, lipid, and carbohydrate respectivelyLiverElaboration of bile acidsGallbladerStorage and concentration of bileSmall intestineFinal intraluminal digestion of foodstuffs, digestion of carbohydrate dimers and specific absorptive pathway for digested materialLarge intestineAbsorption of fluid and electrolyte and products of bacterial action in colon

The organs involved in digestion and absorption has the capacity to increase its activity several fold in response to specific stimulation

Minor functional loss may unnoticed by the individual, allowing the pathology to progress for some time before being diagnosed

Approximately 30 g of digestive enzymes are secreted per day

Exocrine gland

The salivary, gastric mucosa, pancrease

Contain specialized cell for synthesis, packaging, and transport of the enzymes to the cell surface , and thence to the intestinal lumen

All digestive enzymes hydrolyze their substratesThe products of such hydrolytic procedures are oligomers, dimers, and monomers of parent macromolecules

Koolman, 2004

Salivary enzymesThe main function of saliva is not the digestion of nutrients but the conversion of food into a homogeneous mass during mastication

SalivaryProteinsAnti-BacterialBufferingDigestionMineral-izationLubricat-ion &Visco-elasticityTissueCoatingAnti-FungalAnti-ViralCarbonic anhydrases,HistatinsAmylases,Mucins, LipaseCystatins,Histatins, Proline-rich proteins,StatherinsMucins, StatherinsAmylases,Cystatins, Mucins, Proline-rich proteins, StatherinsHistatinsCystatins,MucinsAmylases, Cystatins,Histatins, Mucins,Peroxidasesadapted from M.J. Levine, 1993

Stomach In the stomach the food is mixed, stored for some time then finally discharge into the duodenum

GastrinDistension of the stomachProteins and polypeptide Vagal stimulationPlasma calcium concentrationCirculating catecholamines

Gastrin increases acid secretion and the acid then feeds back to inhibit further gastrin secretionStimulating gastrin secretionPepsinogen and intrinsic factorIncreases gastric motilityStimulates the growth of gastric mucosa

Gastrin

Acid in the antrumBlood-borne factors (secretin, GIP, VIP, glucagon, calcitonin)

Inhibiting gastrin secretion

Gastrointestinal hormones

Gastrin, cholecystokinin, secretin, pancreozimin, enterokrin belongs to the group of gastrointestinal hormones

All of these are formed in the gastrointestinal tract and mainly act in thevicinity of the site where they are formedi. e., they are paracrine hormones

Hormon-hormon penting dalam pengaturan pencernaan usus halus: Sekretin: merangsang kelenjar pankreas mengeluarkan getah yang mengandung bikarbonat. Pelepasan hormon ini distimulasi oleh HCl lambungKolesistokinin: merangsang kontraksi serta pengosongan kandung empedu. Pelepasan hormon ini distimulasi oleh lemak yang bersentuhan dengan mukosa duodenumPankreozimin: merangsang kelenjar pankreas mengeluarkan getah yang kaya enzim; distimulasi oleh hasil-hasil pencernaan proteinEnterokrin: merangsang pengaliran getah intestinHormon-hormon di atas dihasilkan oleh mukosa duodenum(Hardjasasmita, 2004; Price, 1995)

Pancrease secretions

Pancrease secretions

Small intestine enzymesThe glands of the small intestine (the Lieberkhn and Brunner glands), the microvilli of the intestinal epithelium secrete additional digestive enzymes that ensure almost complete hydrolysis of the food components previously broken down by the endoenzymes

ZymogensSome digestive enzymes are potentially so damaging to the cells that synthesizes them that they are secreted as inactive precursors

Among the digestive enzymes, the proteases and phospholipases are dangerous

Once secreted, these zymogens are converted into their active forms. This activation process is irreversible

Pepsinogen pepsin

Trypsinogen tripsin

Chymotrypsinogen chymotrypsin

Proelastase elastase

Procarboxypeptidase carboxypeptidase H+enteropeptidasetripsintripsintripsin

Overview of carbohydrate digestion. Digestion of the carbohydrates occurs first, followed by absorption of monosaccharides. Subsequent metabolic reactions occur after the sugars are absorbed

Lieberman, 2009

Action of salivary and pancreatic -amylases

Lieberman, 2009

Metabolism of Sugars by Colonic BacteriaSome indigestible carbohydrates. These compounds are components of dietary fiberLieberman, 2009

Digestion of triacylglycerols in the intestinal lumenTG, triacylglycerol; bs, bile salts; FA, fatty acid; 2-MG, 2-monoacylglycerol.

Lieberman, 2009

12Action of pancreatic lipase. Fatty acids (FA) are cleaved from positions 1 and 3 of the triacylglycerol, and a monoacylglycerol with a fatty acid at position 2 is producedAction of pancreatic esterases (A) and phospholipase A2 (B)

Absorption of Food Lipids

Digestion of proteins The proteolytic enzymes, pepsin, trypsin, chymotrypsin, elastase, and the carboxypeptidases, are produced as zymogens (the [pro] and [ogen], in red, accompanying the enzyme name) that are activated by cleavage after they enter the gastrointestinal lumen

Lieberman, 2009

Action of the digestive proteasesPepsin, trypsin, chymotrypsin, and elastase are endopeptidases; they hydrolyze peptide bonds within chains. The others are exopeptidases; aminopeptidases remove the amino acid at the N-terminus and the carboxypeptidases remove the amino acid at the C-terminus. For each proteolytic enzyme, the amino acid residues involved in the peptide bond that is cleaved are listed beside the R group to the right of the enzyme name.

Lieberman, 2009

Absorption of Peptides and Amino Acids

Sodium: active absorption in jejunum-ileum. Chloride follow by electromagnetic attraction.

Potassium: passive secretion or absorption, depending on lumenal concentration if diarrhea, hypokalemia due to loss of K+

HCO3-: secreted by pancreas, neutralizes H+ from stomach. Used as a buffer

Calcium: need an active transport to cross the intestinal epithelium. Absorption promoted by a derivative of Vitamin D

Iron: actively reabsorbed. Stored as ferritin

Water: two liters of fluids are taken as food or drink per day. In addition, 7 liters are used to secrete digestive juices need to reabsorb most of H2O.

H2O reabsorbed throughout the small and large intestines. Colon is especially designed to reabsorb H2O.

Colonic bacteria produce some gases such as: CO2, methane, hydrogen, nitrogen, H2SLecithin will be decomposed into choline & neurin

Some amino acids that will be decarboxylated in putrefaction process: Lysin Kadaverin Arginine Agmatin. Tyrosine Tyramin. Ornithine Putressin. Histidine Histamin.These amino acids have strong vasomotor effectTryptopan Indol + Methyl Indol (Skatol) giving specific scent to the faeces

Nitrogen diubah menjadi Amonia ke hati sekresi portal shg pada penyakit sirosis hepatik dan Ca.amonia meninggi dalam darah perifer Toksik Koma Hepatik; Zat Neomycin peroral bisa mengurangi kadar amonia darah.

(Koolman, 2004)

(Koolman, 2004)

Bile acids and bile saltsBile is an important product released by the hepatocytesIt promotes the digestion of fats from food by emulsifying them in the small intestine The emulsifying components of bile, apart from phospholipids, mainly consist of bile acids and bile salts The bile also contains free cholesterol, which is excreted in this way

BILEHeme ProteinCholesterolBiliverdin, bilirubin(Bile pigment)Cholic acid, chenodeoxycholic acid (Bile acids)

(Koolman, 2004)

Meisenberg, G., Simmons, WH. Principles of Medical Biochemistry, 2 ed. Mosby Elsevier, 2006Lieberman, M., Marks, DA. Marks Basic Medical Biochemistry a Clinical Approach 3rd ed. Lippincott Williams and Wilkins, 2009Koolman, J.; Roehm, KH. Color Atlas of Biochemistry, 2 ed. Thieme, 2004; 266-273; 306-315Broom, I. Function of the Gastrointestinal Tract in Medical Biochemistry (Baynes, J.W., Dominiczack, M.H., editors), 2nd ed. Elsevier, 2005.Hopfer, U. Digestion and Absorption of Basic Nutritional Constituents in Textbook of Biochemistry with Clinical Correlations, Devlin, TM (editor), 6th ed. Wiley Liss, 200Bender, D.A., Mayes, P.A. Nutrition, Digestion, and Absorption in Harpers Ilustrated Biochemistry, Murray, RK., Granner, DK., Rodwell, VW(editors), 28th ed., 2009