1-28-10-PDF_40114 - Review What does the pentose phosphate...

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Unformatted text preview: Review What does the pentose phosphate pathway achieve? The pathway yields reducing potential NADPH in the form of NADPH to be used in anabolic reactions requiring electrons. ribose-5-phosphate The pathway yields ribose 5-phosphate. Review A steady supply of NADPH is vital for RBC Review Peroxides are eliminated by reaction with GSH, catalized by glutathione peroxidase GSH is subsequently regenerated by the reduction of GSSH by NADPH as catalyzed by GSH reductase Supplemental Reactive Oxygen Species (ROS) Reactive oxygen species are molecules like hydrogen peroxide (H2O2) and superoxide (O2-) This is an extremely unstable configuration, and radicals quickly react with other molecules. Damage to Lipid, Protein, and DNA Lecture 4 Gluconeogenesis (new glucose synthesis) Biosynthesis of new glucose (i.e. NOT glucose from glycogen) which is which? 1.Glycogenolysis a 2.Glycogenesis b 3.Gluconeogenesis 4.Glycolysis d c a. Degradation of stored glycogen b. Glycogen synthesis c. Biosynthesis of new glucose d. Glucose breakdown Glycolysis Glycolysis Sequence of 10 enzymatic reactions Glucose + 2 NAD+ + 2 ADP + 2 Pi 2 pyruvate + 2 NADH + 2 ATP + 2 H2O + 4 H+ ^ not very effi cient Gluconeogenesis Gluconeogenesis is the process whereby precursors such as lactate, pyruvate, glycerol, and amino acids are converted to glucose When dietary sources of glucose are not available and when the liver has exhausted its supply of glycogen, glucose is synthesized from noncarbohydrate precursours this is when the process is needed! Fasting requires all the glucose to be synthesized from these non-carbohydrate precursors Most precursors must enter the Krebs cycle at some point to be converted to oxaloacetate < most important content in process Oxidative fuel metabolism occurs in cytosol, outside of mitochondria TCA cycle can supply energy source for oxidative phosphorylation Cytric acid cycle and oxaloacetate Oxaloacetate is the starting material for gluconeogenesis end point gluconeogenesis glycolysis starting point Conversion of pyruvate to phosphoenolpyruvate (PEP) IMPORTANT INFO. Conversion of pyruvate to PEP requires the action of two mitochondrial enzymes 1. Conversion of pyruvate to oxaloacetate Pyruvate carboxylase catalyses the ATP-driven formation of oxaloacetate from pyruvate and HCO3 The CO2 in this reaction is in the form of bicarbonate (HCO3-) *86%-90% of CO2 in the body is converted into carbonic acid (H2CO3), which can quickly turn into bicarbonate (HCO3-). 2. Conversion of oxaloacetate to phosphoenolpyruvate PEP carboxykinase (PEPCK) converts oxaloacetate to PEP that uses GTP as a phosphorylating agent PEPCK is not expressed in most extra-hepatic tissues, so the problem is largely confined to the liver Transport between the mitochondria and the cytosol Mitochondrion Mitochondria Mitochondria are membrane-enclosed organelles distributed through the cytosol of most eukaryotic cells. Their main function is the conversion of the potential energy of food molecules into ATP. Every type of cell has a different amount of mitochondria. There are more mitochondria in cells that have to perform lots of work, for example - your leg muscle cells, heart muscle cells etc. Other cells need less energy to do their work and have less mitochondria. Transport of PEP and oxaloacetate from the MT to the cytosol PEP transport systems are seen in the mitochondria but oxaloacetate can not be transported directly in or out of the mitochondria. Gluconeogenesis occurs in the cytosol summary Citric acid cycle is in mitochondria Gluconeogenesis is in cytoplasm MT can not transport oxaloacetate across membrane PEP can be transported from mitochondria Since PEP is a high energy compound, does not need ATP or biotin Malate can be transported and converted to oxaloacetate, which is then converted to PEP The CO2 in this reaction is in the form of bicarbonate (HCO3-) IMPORTANT REACTION! Carbon dioxide (CO2) is somewhat inert (inactive) and requires the energy from ATP hydrolysis to drive the reaction forward. Most enzymes that have CO2 as a substrate require biotin. Pyruvate carboxylase requires biotin as a cofactor Biotin functions as a CO2 carrier by forming a carboxyl substituent at its N1 ureido group Biotin is covalently bound to an enzyme Lys residue to form a bicytin (AKA: biotinyllysine) residue E: enzyme - Activated carboxyl group is transferred from carboxybiotin to pyruvate Exergonic Biotin is an essential nutrient FYI Vitamin A (Retinol) Vitamin B1 (Thiamin) Vitamin B2 (Riboflavin) Vitamin B3 (Niacin) Vitamin B5 (Pantothenic acid) Vitamin B6 (Pyridoxine) Vitamin B7/Vitamin H (Biotin) Vitamin B9 (Folic acid) Vitamin B12 (Cobalamin) Vitamin B13 (Orotic Acid) Vitamin B15 (Pangamic acid) Vitamin B17 (Laetrile) Vitamin C (Ascorbic Acid) Vitamin D (Calciferol) Vitamin E (Tocopherol) Vitamin K (Phylloquinone) Vitamin P (Bioflavonoids) Egg-white injury syndrome Biotin was first recognized as an essential nutrient factor in mammals in 1936. Ten years earlier, the inclusion of large amounts of raw egg whites in experimental diets in rats had produced symptoms of toxicity (e.g. severe dermatitis, loss of hair, and lack of muscular coordination) within a few weeks of the diet being initiated. Biochemical basis for egg-white injury syndrome Raw egg whites are found to contain the glycoprotein avidin, which has a remarkable affinity for biotin. Once a biotin-avidin complex forms, the bond is essentially irreversible; the biotin-avidin complex is not broken. As a result, biotin is not liberated from food. SOLUTION The syndrome could be prevented by heating the egg whites, a process that denatures avidin and destroys its affi nity for biotin. Can the tight binding of avidin to biotin be used as a tool in biochemical analysis? Immobilized Monomeric Avidin and Kit Ideal affinity support for reversibly binding biotinylated proteins Protein purification etc. (affinity purification) PEP carboxykinase (PEPCK) GTP requiring Gluconeogenesis is NOT just the reverse of glycolysis Several steps are different so that control of one pathway does not inactivate the other. However many steps are the same. Three steps are different from glycolysis. 1. Pyruvate to PEP 2. Fructose 1,6- bisphosphate to Fructose-6phosphate 3. Glucose-6-Phosphate to Glucose Gluconeogenesis is not just the reverse of glycolysis gluconeogenesis glycolysis Three steps of interconversions are catalyzed by different enzymes Substrates for Gluconeogenesis Lactate Lactate is a predominate source of carbon atoms for glucose synthesis by gluconeogenesis. During anaerobic glycolysis in skeletal muscle (fast-twitch muscle fibers), pyruvate is reduced to lactate by lactate dehydrogenase (LDH). Lactate produced by the LDH is released to the blood stream and transported to the liver where it is converted to glucose. Glucose is then returned to the blood for use by muscle as an energy source and to replenish glycogen stores. Pathways of Discovery: Cori cycle The Nobel Prize in Physiology or Medicine 1947 "for their discovery of the course of the catalytic conversion of glycogen" Carl Ferdinand Cori Gerty Theresa Cori, née Radnitz USA Washington University St. Louis, MO, USA b. 1896 (in Prague, then Austria) d. 1984 USA Washington University St. Louis, MO, USA b. 1896 (in Prague, then Austria) d. 1957 http://nobelprize.org/nobel_prizes/medicine/laureates/1947/ Pathways of Discovery: Krebs cycle The Nobel Prize in Physiology or Medicine 1953 "for his discovery of the citric acid cycle" Hans Adolf Krebs United Kingdom Sheffield University Sheffield, United Kingdom b. 1900 (in Hildesheim, Germany) d. 1981 http://nobelprize.org/nobel_prizes/medicine/laureates/1953/ Low blood glucose (dietary fuels are not available) Liver Muscle ...
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