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Lec:3 biochemistry Dr. Anwar j almzaiel Digestion and absorption The gastrointestinal tract (G.I.T) The principle function of the gastrointestinal tract and its associated organs is the digestion and absorption of nutrient. The major foods are ingested as macromolecules (carbohydrate, proteins, lipids and nucleic acids), which must be broken down to small components for absorption. This is achieved by enzymes hydrolases secreted by the G.I.T, together with the mechanical process involve in digestion. The digestive sequence is controlled by neural and hormonal factors and the gut is an active endocrine organ. Protein Starch triglycerides amino acid monosaccharides monoacylglycerol, glycerol and fatty acid Digestion: A process of converting complicated compounds from the insoluble, non-diffusible state into simple products of higher solubility and great diffusiblity making easier absorption for utilization by tissue The important digestive secretion are (daily) secretion Vol (ml) pH Salivary secretion 1000 6.8 Gastric juice 1500 1-3.5 Pancreatic juice 1000 8-8.3 Bile juice 1000 7.8 Intestinal juice 1800 7.5-8 Metabolism: Is the network of chemical reactions that occur inside the body (within the cell). It describes all biochemical reactions occurring in 1 Lec:3 biochemistry Dr. Anwar j almzaiel the cell exchanging matter and energy between the cell and its environment. Metabolites are the small molecules that are intermediates in the degradation or biosynthesis of biopolymers. The term intermediary metabolism is applied to the reactions involving these low-molecularweight molecules. Metabolic pathways fall into three categories: 1. Anabolic pathways which are those involved in the synthesis of large and more complex compounds from small molecules for example synthesis of protein from amino acids, synthesis of glycogen from carbohydrates and nucleic acid. Free energy is required for these processes. 2. Catabolic pathways which are involved in the breakdown of large molecules into small molecules, therefore, it is the process of degradation (it can be absorbed and metabolized) for example the respiratory chain and oxidative phosphorylation). 3. Amphibolic pathways which occur at the crossroad of metabolism, acting as links between the anabolic and catabolic pathways After digestion, the simple food materials pass into the cells by a process called “absorption”. So the first part of metabolism is the digestion & absorption. 2 Lec:3 biochemistry Dr. Anwar j almzaiel Mouth Ingestion: In the mouth food is ground, moistened and lubricated by saliva a mucal fluid (secreted by three pairs of salivary glands; parotid, submaxillary, and sublingual glands). It is colourless, opalescent, slimy fluid secreted at a rate of 1500 cc/day, this depends on the type and amount of food. Digestion: salivary glands secrete α-amylase, which digests starch into small segments of α-dextrins, maltose and into individual soluble sugars. Salivary glands also secrete lysozyme, which kills bacteria but is not classified as a digestive enzyme. Then the resulting bolus of food is swallowed into the esophagus and carried by peristalsis to the stomach Composition of saliva Saliva contains 99.4% water and 0.6 solids. The saliva has a pH of 6.8 (natural, slightly acidic) which necessary for working of amylase. Saliva contains two major types of protein (two thirds of total solids, 0.4%): a- α-amylase which is an enzyme for digesting starch b- Mucin (glycoprotein) for lubricating purposes It is also contains some inorganic ions (one third of total solid 0.2%) such as Na+, K+, Ca++, PO4, Cl-, I, - SCN (in the smokers) and HCO3- Function of Saliva 1- Digestive role, catalysing hydrolysis of polysaccharide (starch and glycogen) into dextrin and disaccharide (maltose_ 2- Lubricating of food (due to mucin, which is an excellent compound that facilitates passage of food through G.I.T. 3- For testing 4- Neutralization influence upon some of the acidity of the stomach (due to the presence of machinery and bicarbonate ions) The presence of stone in slivery gland because of presence of NaCl and other salts that precipitate and blockage of silvery gland - α-amylase hydrolase only α 1-4 bonds such as the bonds in starch, it cannot hydrolyse β (1-4) like in cellulose - Some people have acidic pH of saliva because of the presence of organic acid (lactic acid)in their saliva as a result from the bacteria found in the carries of the teeth 3 Lec:3 biochemistry Dr. Anwar j almzaiel Esophagus The esophageal secretions are entirely mucoid in character and principally provide lubrication for swallowing. The food passes to stomach through the peristaltic movement of the esophagus. No digestive juice is secreted in the esophagus, but amylase of the saliva continues its activity during this passage Stomach The main digestion of protein takes place in the stomach. The digestion of carbohydrates and fats is stopped due to the presence of HCl (high acidity). Gastric secretion is initiated by nervous or reflex mechanism; effective stimuli are similar to those of salivary secretion. Secretion is due to hormonal stimulus gastrin, which produced by gastric glands The gastric juice, which is a mixture of HCl, organic material (enzymes) secreted from the gastric gland, which is composed of 3 types of cells: 1- Columnar cells: present in the neck of gastric gland, secret mucin 2- Parietal cells: found in the tubular part of gastric gland, arranged in layers, secrete HCl 3- Chief cells: these are exhibiting a single layer of secreting cells in the neck of gastric gland, secrete HCl, pepsin and other enzymes Function of gastric mucin: a- Protect epithelial tissue from being digested, through its buffering action of the gastric juice to protect the stomach wall from the action of HCl and pepsin and prevents the formation of gastric ulcers b- Provide us with glycoprotein called intrinsic factor that facilitates absorption of Vit. B12 The most common cause of maturation failure is not lack of Vit B12 in the diet, but instead failed to absorb Vit B12 from the G.I.T. This often occurs in the disease called pernicious (malignant) anemia Stimulation of gastric secretion The factors stimulate gastric juice in 3 phases: 4 Lec:3 biochemistry Dr. Anwar j almzaiel a- Cephalic phase: includes the taste, smell and sight of foods b- Gastric phase: includes the presence of food in the stomach, this stimulation due to mechanical and chemical factors which cause the wall of the stomach to secrete hormone called gastrin carried by the blood to the parietal cells of gastric gland to the wall and cause HCl secretion Histamine: also stimulates the secretion of HCl (like gastrin) but has a different structure (produced from removal of CO2 from histidine) c- Intestinal phase: presence of food in the duodenum of intestine stimulates secretion of gastric juice, which is due to hormonal stimulation The composition of gastric juice - Colourless clear fluid and contain about (99.4% water), 0.6% total solids - Chief inorganic substances in gastric juice are HCl and small amounts of NaCl, KCl, PO4-3 - The organic substances are enzymes: a- Pepsin It is produced in the peptic and mucous cells of the gastric glands, and secreted as inactive form pepsinogen and in the cavity it is activated as it come in contact with HCl formed pepsin that cataylase the conversion of protein into polypeptides, proteoses and small particles b-Renine This enzyme is in the infant stomach only and facilitate the digestion of casine of milk and this enzyme after 6 months of age will disappear (it absent in adult) c-Lipase Which is inactive because of low pH, it has minor lipolytic influence when compared with pancreatic and intestinal lipase (hydrolyse triglycerides of short and medium chain length) Hydrochloric acid (HCl) 5 Lec:3 biochemistry Dr. Anwar j almzaiel The parietal cells are the main source of HCl. These cells contain the enzyme carbonic anhydrase, which catalyses the reversible reaction of CO2 with H2O to carbonic acid The HCl conc=170 meq/L pH=0.87 and normality of 0.17 N Davenport theory: according to this theory, plasma CO2 can pass through parietal cells freely. The solubility of CO2 is very low in normal conditions, but by the action of carbonic anhydrase the solubility becomes 100 times more soluble. H2CO3 will then dissociate to give bicarbonate + H+ions. The hydrogen ion in some way is secreted and accompanied with Cl- which is from lymph to form HCl. H2O get out, HCO3 is absorbed into the blood the bicarbonate ions go to the lymph to replace the Cl- ions taken The membrane adjacent to the gastric lumen secretes H+ & Cl.- The HCO3 formed within the cell is passed back to plasma. The Cl- is freely permeable membranes so Cl- comes from plasma enters the cell and then secreted into the lumen. HCO3- will combine with Na+ to form NaHCO3 and increases slightly the pH of the blood, the buffering system of blood, neutralize this alkalinity, then pass away in the urine,i.e. urine will be less acidic. The hydrogen ion needed may come from the following methods: 1- The dissociation of H2CO3 as follows 6 Lec:3 biochemistry Dr. Anwar j almzaiel 2- It may also come from glucose metabolism within mitochondria 3- Or the dissociation of water as result of contact with gastric HCl, proteins are denatured (destruction)this allows the polypeptide chain to unfold, making it more accessible to the action of proteolytic enzymes. The low pH also has the effect of destroying most microorganism entering G.I.T Clinical investigation of gastric function The highly acid nature of gastric juice predisposes to the formation of nonhealing ulcer or slowly healing ulcer in the stomach known as “peptic ulcer” or in the duodenum “duodenal ulcer” - Hyperacidity (hyper chlorohydria): acidity may be associated with hypermotility and rapid emptying of the stomach. This is seen in patients suffering from a duodenal ulcer due to a state of irritation of the lining mucosal membrane. The secretary phase increase secreting high amount of HCl - Hypoacidity (hypochlorohydria): this take place in gastric juice obstruction in patients of chronic illness of the stomach associated with atrophic changes in the gastric lining of the stomach such as chronic gastritis and gastric ulcer. - Achlohydria: when there is no HCl secretion, this is a diagnostic feature of stomach cancer; there might be detected of acidity, but due to organic acids as lactic acid or butyric acid due to fermentation by bacterial flora. i.e. , bacteria can act only in the absence of HCl. Function of HCl 1234- Activates pepsinogen Provides optimum pH for the action of pepsin(acidic medium) Denaturates protein , become easily digested Facilitates absorption of iron, its deficiency causes anaemia 7 Lec:3 biochemistry Dr. Anwar j almzaiel 5- Because of its high acidity, it acts as a germicide, that kills pathogenic bacteria Note Factors inhibit gastric secretion 1- fat presents in large amount in stomach (fatty meal) 2- fat present in the duodenum which gastric secretion and HCl due to: a- it decreases gastric motality b- fat cause the release of hormone called enterogastrone released by duodenal mucosa thus gastric juice and HCl secretion is inhabited Pancreatic Juice It is a clear, watery secretion. It contains (1.5% total solids &98. 5 % water). It has a pH of (8.0-8.3, which is alkaline) depends upon HCO3- concentration. Amount of secreted per day is about (1000 cc) depend on the amount and type of diet. Two thirds of total solids which is equivalent to 1% is organic material and consist mainly of enzymes. Some of these enzymes secreted as zymogens (trypsine, chemotrypsine and procarboxypeptidase) inactive forms which are secreted by pancreases, when reach duodenum, they are activated by an enzyme of intestinal wall called entrokinase. The activation involves hydrolytic removal of a small peptide from the inactive enzymes. Once active trypsine is produced thus in small amounts, it can activate the rest of trypsinogen &chymotrypsinogen (auto catalysis) Carboxyepeptidase secreted probably as aprocarboxyypeptide which is inactive form and activated by trypsin, it acts on the carboxyl group of amino acid in the polypeptides Function of trypsin 8 Lec:3 abcd- biochemistry Dr. Anwar j almzaiel Protein digestion Auto catalysis Chymotrypsinogen activation Procarboxy peptide activation 4. Lipase: hydrolyse lipid into glycerol or fatty acid and monoglycerides 5. Amylase: which hydrolyse α1-4 glycosidic linkages in polysaccharides (like starch into amylopectine or glycogen into maltose) 6. Cholesterol esterase: hydrolyse cholesterolester into cholesterol and fatty acids 7. Ribonuclease:hydrolyse ribonucleic acid (RNA) into nucleotides 8. Deoxyribonuclease:hydrolyse deaoxyribonucleic acid(DNA) into nucleotides 9. Collagenase: hydrolyse collagen in diet (muscle &tissue) 10. Phosphatase: can remove phosphate from organic substances All these enzymes act in either neutral or slightly alkaline One third of the solid (0.5%) is inorganic material & consist mainly of the Cl - & HCO3- and Na+ . They function to neutralize the HCl action in stomach 9 Lec:3 biochemistry Dr. Anwar j almzaiel & provide alkaline pH for the action of these enzymes which act on neutral or alkaline media. The other inorganic materials which present in small amounts K+, Ca+ & PO4+ Secreted from different intestinal glands in mucosa at intestinal and duodenum from the gland called Brunner LieberKuhn gland. The juice contains desquamated epithelial cells, leukocytes and mucus. Intestinal juice contains 98.5% water and 1.5% total solids. The organic solids contain enzymes, musin, phosphate lipids and enzyme like substances, pH= 7.0-8.0 The enzymes are: 1- Nucleotidase: hydrolse the nucleotide into nucleoside with PO4-3 Nucleotide: nitrogen base, ribose & phosphoric acid Nucleoside: nitrogen base and ribose only 2- Nucleosidase: converts nucleoside to nitrogen base & pentose sugar (ribose) 3- Maltase: converts maltose to 2 molecules of glucose 4- lactase: converts lactose to glucose and galactose 5- Sucrase: converts sucrose to glucose and fructose 6- Amino peptidase: hydrolyze the polypeptide release amino of the polypeptide to dipeptide 7- Dipeptidase: hydrolyze the didpeptide into a.a.(amino acids) 8- phospholipases: convert the phospholipid to fatty acids (saturated & unsaturated), PO4- , glycerol and nitrogen 9- Phosphatases: remove the phosphate group from organic compound & phosphate will be available to be absorbed the 10 Lec:3 biochemistry Dr. Anwar j almzaiel inorganic solid (Na+, Cl-, HCO3-, K+, Ca++, PO4-3) are similar as that found in the pancreatic juice The intestinal juice secretion is stimulated by hormone called ‘Enterocrinin’ which is produced from Duodenum & jejunum 11 Lec:3 biochemistry Dr. Anwar j almzaiel Bile is secreted in the small intestine; it isn’t digestive secretion & contains no enzymes but help in digestion, secreted at site of pancreatic juice. It helps in digestion of fat and its absorption. Bile is secreted by the liver and collected in the gall bladder, stored & undergoes concentration; therefore we’ve bile with its main constituents of organic material which is bile pigment, mucin, cholesterol, bile acids and salts. Bile acids may increase when we have inflammation in stomach or gall bladders, its increased in the blood of liver in case of cancer, so bile acids are marker if there’s any damage in the gall bladder of liver or any change in bile itself The volume secreted per day 500-1000 ml The bile acids are cholic acids; there are 3 types of bile acids: - Cholic acid - Deoxycholic acid - lithocholic acid These cholic acids are conjugated with a.a like Tyrosine tyrocholic acid or may be conjugated with a.a. like glycine glycine glycocholic acid 12 Lec:3 biochemistry Dr. Anwar j almzaiel These are known as bile salt, these bile acids and salts are synthesized by liver from cholesterol by oxidation of the side chain of the molecule to give cholic acid, and they are soluble in water. Function of bile salt 1- Breakdown protein molecule to very small particles 2- Increase surface area of fat molecules to be acted by enzyme lipase for digestion of fat. 3- Highly emulsion agents, breakdown fat molecules into small particles and decrease the surface tension of water, thus increase the surface area of fat molecule to be acted by enzyme lipase for digestion of fat 4- Facilitate the action of pancreatic lipase by shifting pH to be optimum for lipase activity (6.5-8) 5- They form miscells with fatty acids & mono and diglycerides 6- It stimulates intestinal peristalsis (movement of intestine) help in absorption of diet and pass of feces 7- Stimulate the liver to produce and synthesize of bile, this is due to the mechanism by the action of hormones 13