LEC:2 biochemistry date:14/10/2014 Dr. Anwar J almzaiel Digestion and absorption 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 1 LEC:2 biochemistry date:14/10/2014 - 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 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 2 LEC:2 biochemistry date:14/10/2014 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: 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) 3 LEC:2 biochemistry date:14/10/2014 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) 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. 4 LEC:2 biochemistry date:14/10/2014 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 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. 5 LEC:2 biochemistry date:14/10/2014 Function of HCl 12345- 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 Because of its high acidity, it acts as a germicide, that kills pathogenic bacteria 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 abcd- Protein digestion Auto catalysis Chymotrypsinogen activation Procarboxy peptide activation 6 LEC:2 biochemistry date:14/10/2014 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 & 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+ 7