Lec:5 biochemistry Dr. Anwar J amzaiel sodium–potassium pump (Na-K pump) The single most important process that takes place in the small gut, which makes nutrient absorption possible, is the establishment of an electrochemical and concentration gradient of sodium across the epithelial cell boundary of the lumen. To remain viable, all cells of the body are required to maintain a low intracellular concentration of sodium. Low intracellular sodium concentration is maintained by a large number of Na+K+ ATPases, so-called sodium–potassium pumps The transport of sodium creates both an electrical and a chemical gradient across the plasma membrane. In turn this provides: • a cell’s resting membrane potential, the gradient of which is the basis for excitability in nerve and muscle cells • export of sodium from the cell, providing the driving force for several facilitated transporters, which import glucose, amino acids and other nutrients into the cell • translocation of sodium from one side of an epithelium to the other, creating an osmotic gradient that drives absorption of water. Cells contain huge numbers of these pumps. Abnormalities in the number or function of Na+K+-ATPases are thought to be involved in several pathologic states, in particular heart disease and hypertension. Absorption of lipids The products of lipid digestion include a mixture of partially hydrolyzed lipids (primarily, monoacylglycerols and lysophospholipids), free fatty acids, cholesterol fat-soluble vitamins, and other lipophilic molecules (e.g., carotenoids). The main bulk dietary fat of man is triacylglycerol with mixed long chain fatty acids. No hydrolysis of fat in the stomach(i.e. 1 Lec:5 biochemistry Dr. Anwar J amzaiel no lipase). The suspension must be rendered water-soluble so they can enter the intestine cells. All the products of lipid digestion ultimately become solubilized by bile salts to form small mixed micelles that diffuse from the lumen of the intestine toward the duodenum and jejunum, where the dietary lipids undergo lipolysis by pancreatic lipase and absorbed. Whereas absorbed glucose can readily be transported as such to the liver and other tissues in the bloodstream, this process is not suitable for free fatty acids, because of both their limited solubility and their detergent properties, which could disrupt cell membranes and inhibit enzymes. Although free fatty acids released from adipocytes are transported in plasma bound to serum albumin, the higher concentrations of free fatty acids present after a meal would overwhelm this transport system. Instead, the absorbed fatty acids are reesterified into less polar products for transport in the form of large lipoprotein aggregates called chylornicrons. Triacylglycerol also is packaged with cholesterol, lipoproteins and other lipids into chylomicrons. the hydrolysed cholesterol ester and the free cholesterol together with most of the biliary is absorbed after transportation in the micelles. the mixed micelles penetrate the membrane of the cell either by dissolving in the membrane or by a process of pincytosis Bile acids and pancreatic lipase act in the lumen to emulsify and digest triacylglycerols into their monoacylglycerols and free fatty acids. Bile, stored in the gall bladder and released into the duodenum, contains the bile salts, sodium glycocholate and sodium taurocholate. Such amphipathic molecules have a ‘detergent effect’ on lipids, intercalating and breaking them down to smaller aggregates, and eventually to 2 Lec:5 biochemistry Dr. Anwar J amzaiel micelles (4–8 nm diameter), thereby enabling the action of pancreatic lipase. Absorption of Proteins Protein is digested in the stomach and intestine to peptide and amino acid, where proenzymepepsinogen is autocatalytically converted to pepsin A. Most proteolysis takes place in the duodenum via enzymes secreted by the pancreas, including trypsinogen, chymotrypsinogen and pro-carboxypeptidase These proteases are produced in the form of their respective proenzymes; thier combined action leads to the production of amino acids, dipeptides and tripeptides. Enterokinase, activates trypsinogen into trypsin, which in turn converts a number of precursor pancreatic proteases into their active forms. The mechanism by which amino acids are absorbed is conceptually identical to that of monosaccharides. In health about 90% of the proteins are absorbed at very high rate. Most natural a.a is L-isomer which transport actively against concentration gradient. D.isomer transport passively at much slower rate to the portal blood Hartnup disorder is an autosomal recessive impairment of neutral amino acid transport affecting the kidney tubules and small intestine. It is believed that the defect is in a specific system responsible for neutral amino acid transport across the brush-border membrane of renal and intestinal epithelium, but the defect has not yet been characterised 3