Unit 1: Intermediary Metabolism (PDF)

Unit 1: Intermediary Metabolism Biochemistry, 8th Edition by Campbell and Farrell.  Metabolism Metabolism: Sum of all chemical reactions in a cell or organism. ▪ Pathway: A series of biochemical reactions. ▪ Catabolism: Breakdown of large nutrient molecules i...

Unit 1: Intermediary Metabolism Biochemistry, 8th Edition by Campbell and Farrell.  Metabolism Metabolism: Sum of all chemical reactions in a cell or organism. ▪ Pathway: A series of biochemical reactions. ▪ Catabolism: Breakdown of large nutrient molecules into smaller molecules with the concurrent production of energy. ▪ Catabolism is generally accompanied by the net release of energy.  Metabolism Metabolism: Sum of all chemical reactions in a cell or organism. ▪ Pathway: A series of biochemical reactions. ▪ Anabolism: Production of biological macromolecules through biosynthesis ▪ Anabolism requires a net input of chemical energy.  Metabolism Metabolism: Sum of all chemical reactions in a cell or organism. ▪ Catabolic and anabolic pathways with the same end points are not simple reversals of each other – each pathway must be thermodynamically favorable in its own direction.  Metabolism Metabolism: Sum of all chemical reactions in a cell or organism. ▪ Metabolic pathways are regulated by several mechanisms, including control of enzyme concentration, enzyme activity, and enzyme compartmentation. Overview of Metabolism Overview of Metabolism  Digestive System and Digestive Juices ▪ Digestion: the process by which food is broken down into components simple enough to be absorbed in the intestine. ▪ The mouth, stomach and duodenum deal with the initial process of mixing ingested food and initiating digestion. ▪ In the duodenum, bile and pancreatic secretions enter through the common bile duct. ▪ The small intestine is the main digestive area: in the jejunum digestive process continue and absorption is initiated; it continues to the ileum. ▪ The large intestine (cecum, colon and rectum; primarily the colon) is involved in the absorption and secretion of electrolytes and water.  Digestive System and Digestive Juices ▪ Most digestive enzymes are secreted as inactive precursors ▪ With the exception of salivary amylase and lingual lipase, digestive enzymes are secreted into the gut lumen as inactive precursors termed as zymogens. ▪ Secretion of enzymes is similar in the salivary glands, gastric mucosa and pancreas. They contain specialized cells for synthesis, packaging and transport of zymogen granules to the cell surface and thence to the intestinal lumen.  Digestive System and Digestive Juices ▪ Most digestive enzymes are secreted as inactive precursors ▪ Enzymes involved in digestion of protein (protease) and fat (Lipase: phospholipase A2) are synthesize as inactive zymogens and are only activated on their release to the gut lumen. ▪ Once active, they can activate their own precursors. ▪ Activation of precursors can also occur by change in pH (pepsinogen in the stomach is converted to pepsin at pH of 4.0) or by action of specific enteropeptidase bound to the mucosal membrane of the duodenum.  Digestive System and Digestive Juices ▪ Digestion is a sequential, ordered series of processes ▪ Lubrication and homogenization of food with fluids secreted by glands of the intestinal tract, starting in the mouth. ▪ Secretion of enzymes that break down macromolecules to a texture of oligomers, dimers and monomers. ▪ Secretion of electrolytes, hydrogen ions and bicarbonate within different parts of the GI tract to optimize the conditions for enzymic hydrolysis. ▪ Secretion of bile acids to emulsify dietary lipid, facilitating enzymic hydrolysis and absorption. ▪ Further hydrolysis of oligomers and dimers by membrane-bound enzymes (jejunum) ▪ Specific transport of digested material into enterocytes and thence to blood or lymph. ▪ Recycling of bile acids. Absorption of the SCFAs produced by colonic bacterial fermentation ▪ Reabsorption of water and electrolyte. Digestive System and Digestive Juices Digestive System and Digestive Juices Digestion and Absorption of Carbohydrates  Digestion and Absorption of Carbohydrates ▪ Carbohydrate digestion: begins in the mouth ✓ Salivary enzyme “α-amylase” catalyzes the hydrolysis of α-glycosidic linkage of starch and glycogen to produce smaller polysaccharides and disaccharide – maltose ✓ Only a small amount of carbohydrate digestion occurs in the mouth because food is swallowed so quickly into the stomach. ▪ In stomach, very little carbohydrates is digested ✓ No carbohydrate digestion enzymes in stomach ✓ Salivary amylase gets inactivated because of stomach acidity ▪ The primary site for the carbohydrate digestion is within the small intestine ✓ Pancreatic α-amylase breaks down polysaccharide chains into disaccharide - maltose ▪ The final step in carbohydrates digestion occurs on the outer membranes of intestinal mucosal cells. ✓ Maltase – hydrolyzes maltose to glucose ✓ Sucrase – hydrolyzes sucrose to glucose and fructose ✓ Lactase – hydrolyzes lactose to glucose and galactose  Digestion and Absorption of Carbohydrates ▪ Glucose, galactose, and fructose are absorbed into the bloodstream through the intestinal walls. ▪ Galactose and fructose are converted to products of glucose metabolism in the liver. ▪ Following absorption, the monosaccharide are carried by the portal vein to the liver where galactose and fructose are enzymatically converted to glucose intermediates that enter into the glycolysis pathways. ▪ The glucose may then pass into the general circulatory system to be transported to the tissues or converted to glycogen reserve in the liver ▪ The glucose in the tissues may be ✓ Oxidized to CO2 and H2O (ATP) ✓ Converted to fat ✓ Converted to muscle glycogen Digestion and Absorption of Carbohydrates Digestion and Absorption of Lipids  Digestion and Absorption of Lipids ▪ Dietary Lipids: 98% triacylglycerols (TAGs): Fats and oils ▪ Salivary enzymes (water soluble) in the mouth have no effect on lipids (TAGs) which are water insoluble ▪ In stomach: most, not all, of TAGs change physically to small globules or droplets – called chyme which floats above other material: ▪ Lipid digestion starts in the stomach: ✓ Gastric lipase hydrolyzes ester bonds – 2 fatty acids and one monoacylglycerol – about 10% of TAGs are hydrolyzes ✓ High fat foods stay in stomach for longer time – high fat meal gives you a feeling of being full for longer time ✓ For infants, they contain salivary lipase. Thus, lipid digestion starts in the mouth.  Digestion and Absorption of Lipids ▪ Chyme enters into small intestine and is emulsified with bile salts. ▪ Pancreatic lipase hydrolyzes ester bonds to form fatty acids and glycerol ✓ Normally, 2 out of 3 fatty acids are hydrolyzed ▪ Fatty acids, monoacylglycerol and bile salts make small droplets: called micelles – hydrophobic chain in the interior ▪ Micelles consist of monoacylglycerols and free fatty acids: ✓ Small enough to absorb through intestinal cells ▪ In the intestinal cells, monoacylglycerols and free fatty acids are repackaged to form TAGs ▪ Those new TAGs combine with membrane lipids (phospholipids and cholesterol) and lipoproteins to form chylomicrons ▪ Chylomicrons transport TAGs from intestinal cells to the bloodstream through the lymphatic system  Digestion and Absorption of Lipids ▪ From the lymphatics, the fats flow through the thoracic duct into the bloodstream and then to the liver. ▪ In the liver, some of the fats are changed to phospholipids, so the blood leaving the liver contains both fats and phospholipids ▪ These phospholipids, such as sphingomyelin and lecithin are necessary for the formation of nerve and brain tissue ▪ Lecithins are also involved in the transport of fat to the tissue ▪ Cephalin, another phospholipid, is involved in the normal blood clotting ▪ From the liver, some fat goes to the cells through the bloodstream.  Digestion and Absorption of Lipids ▪ In the bloodstream, TAGs are completely hydrolyzed by lipase enzymes ▪ Fatty acids and glycerol are absorbed by the cell and are either broken down to the acetyl-CoA for energy or repacked to store as lipids ▪ The fat in excess of what the cells need is stored in specialized cells called adipocytes (the largest cell in the body) in the adipose tissue ✓ Located primarily beneath the skin especially in the abdominal region and vital organs ✓ Adipose tissue also serves as a protection against the heat loss and mechanical shock ▪ Triacylglycerol energy reserves (fat reserves) are the human body’s major source of stored energy ✓ Energy reserves associated with protein, glycogen, and glucose are small to very small when compared to fat reserves Digestion and Absorption of Lipids Digestion and Absorption of Proteins  Digestion and Absorption of Proteins ▪ Protein digestion (denaturation and hydrolysis) starts in the stomach: ✓ Dietary protein in stomach promotes release of gastrin hormone which promotes secretion of pepsinogen and HCl; HCl in stomach has 3 functions: Gastric acidity denatures protein thereby exposing peptide bonds Gastric acidity (pH of 1.5-2.0) kills most bacteria Activates pepsinogen (inactive) to pepsin (active) ✓ Enzyme pepsin hydrolyzes about 10% peptide bonds ▪ Large polypeptide chains pass from stomach into small intestine: ✓ Passage of acidified protein promotes secretion of “Secretin” hormone which stimulates: Bicarbonate (HCO3-) production which in turn helps neutralize the acidified gastric content Promotes secretion of pancreatic digestive enzymes trypsin, chymotrypsin and carboxypeptidase in their active forms.  Digestion and Absorption of Proteins ▪ Protein digestive enzymes in intestine: ✓ Enzymes (Trypsin, chymotrypsin, carboxypeptidase and aminopeptidase) are produced in inactive forms called zymogens and are activated at their site of action ✓ Trypsin, chymotrypsin and carboxypeptidase in pancreatic juice released into the small intestine help hydrolyzed proteins to smaller peptides ✓ Aminopeptidase secreted by intestinal mucosal membrane further hydrolyze the small peptides to amino acids ✓ Amino acids liberated are transported into bloodstream via active transport process Digestion and Absorption of Proteins Summary of Intermediary Metabolism Summary of Intermediary Metabolism