Biochem lec 1+2.pdf

Biochemisty lec# 1- Digestion and Absorption of Basic Nutritional Constituents Nutrients types - Digestible o Proteins o Carbohydrates o Fats (Lipids) o Nucleic acids - Indigestible (Fibers)  indigestible in humans because we are missing...

Biochemisty lec# 1- Digestion and Absorption of Basic Nutritional Constituents Nutrients types - Digestible o Proteins o Carbohydrates o Fats (Lipids) o Nucleic acids - Indigestible (Fibers)  indigestible in humans because we are missing the necessary enzymes. o Cellulose o Pectin (complex mixture) o Others Digestion, Absorption and transport of carbohydrates - Starch - Lactose - Sucrose - Important to note that we can only absorb molecules that we can breakdown, so if we don’t have the proper enzyme we can’t break it down (ex, cellulose) Overview of carbohydrate digestion  - Start out as large molecules (polysaccharides)  starts to be broken down into smaller molecules (dextrins) by salivary and pancreatic amylase  then the remaining disaccharides are broken by disaccharidases (ex, maltase) found on the brush borders down into monosaccharides  which can then be absorbed. DIETARY CARBOHYDRATES  - 40 to 45% of caloric intake in USA diet. 50-60 % came from starch - The animal origin carbs is lactose (milk and milk products) - Sucrose and small amounts glucose and fructose are the major natural sweeteners found in fruit, honey, and vegetables. Inter-conversion of Monosaccharaides  amino acids that generate glucose are called glucogenic amino acids (9). These molecules give rise to pyruvate which can then be converted into glucose via gluconeogenesis. GI System - Biochem DIGESTION OF DIETARY CARBOHYDRATES - Glycosidase exhibit some specificity for the glycosidic bond and number of residues. If the carbs remain undigested because it was not broken down by the proper enzyme  they are fermented by the gut bacteria  this will give us the watery content of the feces. - That’s why when someone has food poisoning  the brush borders where the enzymes are located are damaged  leading to an increased amount of carbs being fermented by bacteria  giving us diarrhea Salivary and Pancreatic-Amylase - Breaks down large molecules of starch into different molecules  maltose, isomaltose, limit dextrins, and trisaccharides  each needing its own enzyme to be broken down. - 1 L of saliva/Day. 1.5 L of pancreatic juice/Day - Limit dextrins: are oligosaccharides (4 -9 residues with one or more α-1,6 branches). Disaccharidases of the Intestinal Brush-Border Membrane - Some enzymes come in the form of complexes that can work on different substrates. 1. Maltase-GLUCOAMYLASE  Glucoamylase is similar to the sucrase–isomaltase complex structures. It is an exoglucosidase that is specific for the α–1,4 bonds begin at the non-reducing end of a polysaccharide or limit dextrin. 2. SUCRASE–ISOMALTASE COMPLEX  Similar structure to the glucoamylase GI System - Biochem - This diagram shows us what bonds these complexes break down: 3. Trehalase  Has only one catalytic site. Trehalose (insects, algae, mushrooms, and other fungi) is not currently a major dietary component. Cleaves the α-1,1 bond (‫)سنوات‬  Trehalase deficiency (a woman became very sick after eating mushrooms and was initially thought to have α–amanitin poisoning). 4. GLYCOSIDASE COMPLEX (LACTASE-GLUCOSYLCERAMIDASE)  Hydrolyzes the -bond connecting glucose and galactose in lactose  Around 25% of Jordan has lactose intolerance.  With age, lactose intolerance increases because this enzyme is the first to be damaged when there is an injury to the GI and the last to be repaired. LOCATION WITHIN THE INTESTINE - The production of maltose, maltotriose, and limit dextrins by pancreatic –amylase occurs in the duodenum - Sucrase–isomaltase, β-Glycosidase activity is highest in the jejunum - Glucoamylase activity progressively increases along the length of the small intestine, and its activity is highest in the ileum. Metabolism of Sugars by Colonic Bacteria - Starches high in amylose, or less well hydrated (e.g., starch in dried beans), are resistant to digestion and enter the colon. - Dietary fiber and undigested sugars also enter the colon. - Any carbohydrate remaining undigested will be fermented by gut bacteria Indigestible carbohydrates - Humans lack the necessary enzymes to breakdown the bonds: GI System - Biochem - LACTOSE INTOLERANCE  caused by low levels of lactase o Adult levels are less than 10% of that present in infants (lactase non- persistence phenotype). o When the levels of lactase remain at, or only slightly below infant levels throughout adulthood (lactase persistence phenotype) o Table is not for memorization, only to consider. - Intestinal injury  Lactase is usually the first activity lost and the last to recover. - Glycemic index  Glucose and maltose have the highest o The glycemic index is a value assigned to foods based on how quickly and how high those foods cause increases in blood glucose levels. o Absorption of monosaccharides  - Certain transporters are needed to bring in these monosaccharides into the blood - Facilitated diffusion  the carrier itself is not using the ATP, indirect active transport GI System - Biochem - 14 types of GLUTS  different tissues use different carries, depending on their glucose requirement and their response to insulin (insulin dependent vs insulin independent) - GLUT2 function can be seen in insulin stimulation  the influx of glucose from the GLUT2 carrier causes the release of insulin - GLUCOSE TRANSPORT THROUGH THE BLOOD-BRAIN BARRIER AND INTO NEURONS  in order for glucose to enter the CNS, it needs specific carriers (ex, GLUT3), to make sure only glucose is allowed in to the brain. Digestion and Transport of Dietary Lipids - DIGESTION OF TRIACYLGLYCEROLS  Triacylglycerols are the major fat in the human diet - Can be saturated or unsaturated - Digestion begins in the mouth by lingual lipase. - Secretion of the bile salts from the gallbladder help in the digestion of lipids. - The bile salts work by facilitating the absorption of lipids. It doesn’t activate lipase (‫)سنوات‬. - The colipase binds to the dietary fat and to the lipase, thereby increasing lipase activity. - Fatty acids are cleaved from position 1 and 3 from a triacylglycerol into 2- monoacylglycerol which can then be packed into micelles. GI System - Biochem  - Short- and medium-chain fatty acids (C4 to C12) do not require bile salts for their absorption. - When inside the endothelial cells, the triacylglycerol is reformed  and with the addition of certain proteins (apoB)  a new lipid structure is formed  a chylomicron - Certain apolipoproteins are needed for the further processing of chylomicrons. - Cholesterol and phospholipid are broken down by their respective enzymes. - Recycling of bile salts  most of the bile salts synthesized are reabsorbed in the distal ilium Protein Digestion and Amino Acid Absorption - First site of digestion starts in the stomach. - Similar to carbs and fat  peptides needed to be broken down into di and tri peptides by specific peptidases  then aborbed - Proenzymes are needed to be activated  - Aminopeptidases, located on the brush border, cleave one amino acid at a time from the amino end of peptides. - Intracellular peptidases act on small peptides that are absorbed by the cells. GI System - Biochem Lec# 2- Liver metabolism - Hepatocytes (parenchymal cells)  make up 80% of the liver volume o Responsible for almost all pathways of metabolism o Replaceable. Have an ability to regenerate MAJOR FUNCTIONS OF THE LIVER - Ketone Body Formation - The Liver Is a Central Receiving and Recycling Center for the - Nucleotide Biosynthesis Body. - Synthesis of Blood Proteins- almost - Inactivation and Detoxification of Xenobiotic Compounds all of the blood proteins are and Metabolites synthesized in the liver. - Regulation of Blood Glucose Levels - The Synthesis of Glycoproteins and - Synthesis and Export of Cholesterol and Triacylglycerol Proteoglycans - Detoxifies ammonia by using the urea cycle - The Pentose Phosphate Pathway FUELS FOR THE LIVER - Consumes approximately 20% of the body oxygen- the liver is not supposed to consume a lot of energy because it is needed for other metabolic activities in the body. - The principle forms in which energy is supplied 1. Adenosine triphosphate (ATP) 2. Uridine triphosphate (UTP) 3. Guanosine triphosphate (GTP) 4. Reduced NADPH- not an energy supplying molecule however it is used for anabolism. 5. Acyl-CoA thioesters How the body deals with certain molecules during the fed state vs. fasting state  In the Fed state: - Glucose is taken up by the liver and is either: o Converted to glycogen and stored. o Sent to the pentose phosphate pathway which generates NADPH, used as a reducing agent. o Converted to pyruvate for energy - Chylomicron remnants are taken up and generate fatty acids and then triacylglycerol. - Acetyl CoA is the connection between carbohydrates, proteins and lipids. - So just remember  glucose is used for multiple pathways, lipids will be broken down to other lipids which can be stored if the body has enough energy. GI System - Biochem In the fasting state: - The liver must maintain the blood sugar level by breaking down glycogen or by gluconeogenesis. - Another source of energy is the breakdown of lipids to generate ketone bodies. - Protein help in the formation of glucose (glycogenic amino acids) or ketone bodies (ketogenic amino acids) - So just remember  the liver is consuming material to maintain the energy source for the body. Carbohydrate Metabolism in the Liver Glucose as a Fuel - The Km for (GLUT2) and glucokinase is so high (approximately 10 mM)- a high Km means that it needs high concentration to work well. - Glucose will enter after its concentration rises to 10 to 40 mM in the portal blood. - Glycogen synthesis will be increased - Glycolysis will be increased - F. A. Synthesis will be increased - The first step of glycolysis is catalyzed by gluco-kinase (GK)  the function of GK is regulated by glucokinase regulatory protein (GKRP), this enzyme will remove GK from the cytosol making it inactive  the balance of available GK in the cytosol is defined by the amount of glucose (+) vs. fructose 6-phosphate (-). GI System - Biochem  - Another way glycolysis is being regulated is by pyruvate kinase  high amounts of glucagon (low glucose levels)  will phosphorylate pyruvate kinase, inactivating it  and the opposite is true if we have high glucose levels. - The major regulatory step for liver glycolysis  the PFK-1 step (‫)سنوات‬ HORMONAL REGULATION OF GLYCOLYSIS  Regulation of GLYCOLYSIS  *No need to memorize these pathways just see glycolysis is con In summary: GI System - Biochem Lipid Metabolism - Long-chain fatty acids are a major fuel for the liver during periods of fasting. - PEROXISOMAL OXIDATION OF VERY-LONG-CHAIN FATTY ACIDS- the breakdown of these molecules happens in the peroxisome instead of the mitochondria. - De novo synthesis of fatty acids  o Citrate causes the polymerization and activation of acetyl CoA carboxylase which forms malonyl CoA  this happens in the well fed state. o Long-chain fatty acyl CoA acts as a negative feedback and will inhibit this process. - In order to synthesize fatty acids you need glycerol 3-phosphate which can come from the liver or adipose tissue  - KETONE BODIES: AN ALTERNATE FUEL FOR CELLS  - Ketone bodies produced in the liver transported to the blood system to peripheral tissues. - Liver is unable to use ketone bodies because it lacks the thiophorase enzyme. GI System - Biochem  Amino acid metabolism - A list of nitrogen containing compounds that are produced in the liver. - And some other types of proteins that are made in the liver. - No need to memorize anything just read through it. - Pathway of protein absorption, uptake, degradation into the urea cycle and then excretion  - Glucose-alanine cycle: o Alanine produced by peripheral tissue acts as an ammonium carrier  travels to the liver for breakdown into ammonia and pyruvate  ammonia can then be excreted as urea and pyruvate and be used again for generation of glucose. GI System - Biochem - Liver is the principle site of amino acid metabolism in humans. o The liver contains all the pathways for catabolism of all of the amino acids and can oxidize most of the carbon skeletons to carbon dioxide. o It contains the urea cycle. o After a mixed or high-protein meal, the gut uses dietary aspartate, glutamate, and glutamine as a fuel (during fasting the gut uses glutamine from the blood as a major fuel). o The branched-chain amino acids (valine, leucine, and isoleucine) can be used by most cell types as a fuel, including cells of the gut and skeletal muscle. o Most tissues transfer the amino acid nitrogen to the liver to dispose of as urea o The liver uses amino acids for the synthesis of proteins that it requires as well as for the synthesis of proteins to be used elsewhere. - Fed state  - Fasting state  GI System - Biochem