Melody Daroogar OH: Monday 11 – 11:50am [email protected] At Roma Café Handout 3 (Week 4)Melody Daroogar OH: Monday 11 – 11:50am [email protected] At Roma Café I. Glucose Metabolism A. Glycolysis (see figure 14-2): 1. glycolysis takes place in the cytosol 2. Net outcome of glycolysis: 2 pyruvate, 2NADH, 2ATP 3. One glucose molecule (6 Carbon atoms) is partially broken down into two 3 Carbon molecules (pyruvate). Pyruvate then enters other processes and goes through changes to release more energy. 4. To memorize ☺: all the intermediates of glycolysis, their names and their structures. Also, memorize the names of enzymes. 5. Substrate level Phosphorylation: a. is the phosphorylation of ADP coupled to the hydrolysis of an energy-rich comound; independent of the electron transport chain. b. In glycolysis, this happens twice. The first is the reaction going from 1,3-bisphosphoglycerate (mixed anhydride) to 3-phosphoglycerate. ATP is made in this step by transferring a phosphate group from 13BPG to ADP. The second time we see SLP is in the last step of glycolysis: PEP + ADP Pyuvate + ATP 6. Schiff Base formation: a. A Schiff base is formed in the step between fructose 1,6-bisphosphate and DHAP + GAP. See figure 14-5 for the mechanism (don’t memorize the mechanism, but understand what happens. Also, be able to identify what part of the molecule is the Schiff base) B. Post-glycolysis: Anaerobic conditions: (see pg. 538) 1. in yeast and some bacteria: pyruvate CO2 + acetaldehyde (ethanal) + NADH ethanol + NAD+ a. the first step is catalyzed by pyruvate decarboxylase and uses the cofactor TPP b. the second step is catalyzed by alcohol dehydrogenase (cofactor NADH) 2. in humans: pyruvate + NADH Lactate + NAD+ This reaction is catalyzed by the enzyme: lactate dehydrogenase (cofactor: NADH) a. when O2 is scarce in the muscles b. can later be transported to live and converted to glucose (gluconeogenesis) c. is acidic (lactate = lactic acid) so can lower pH of blood C. TPP: Thiamine Pyrophosphate (see figure 14-13) 1. recognize structure of TPP (involved in decarboxylation reactions) 2. Identify the “business end” of the molecule. The other parts of the molecule help align the cofactor with the enzyme and the other substrates.Melody Daroogar OH: Monday 11 – 11:50am [email protected] At Roma Café II. Regulation of Glucose Metabolism A. Phosphofructokinase-1 (PFK-1): 1. 2 active sites and 2 regulatory sites. 2. ATP binds to both these sites. 3. PFK-1 activity is high when ATP levels are low. When ATP levels are low, the active site has the higher affinity for ATP (to increase glycolysis). When ATP levels are high, it will bind to the regulatory sites, thus decreasing the activity of the enzyme. (See figure 15-18 b and c) 4. 3 main enzymes where regulation of glycloysis occurs: a. Hexokinase, PFK-1, Pyruvate kinase (the 3 kinases) b. These enzymes can be regulated through covalent modifications III. Feeder Pathways for Glycolysis (see pgs. 534-537) A. Fructose - when phosphorylated at the 1 and 6 positions, it is broken into DHAP and GAP (glycolysis) B. Galactose – with the help of UDP, is converted to glucose (C4 is different) C. Mannose – can be converted to fructose glycolysis (C2 is different)Melody Daroogar OH: Monday 11 – 11:50am [email protected] At Roma Café D. UDP-glucose (p. 565) memorize structure 1. know the reactions and steps involved in the conversion of galactose to glucose-1-phosphate 2. epimer: molecules that differ in their spatial arrangements around a single carbon atom. E.g. mannose and glucose are epimers (OH on C4 is different in each) IV. Glycogenolysis A. Glycogen is a polymer of glucose: (glu)n B. Glycogen is broken down in the liver by 3 enzymes: 1. glycogen phosphorylase 2. glycogen debranching enzyme 3. phosphoglucomutase C. Glycogen Phosphorylase (see figure 15-3) 1. only glucose molecules from the non-reducing end are broken off the glycogen molecule (reducing end is where the hemiacetal Carbon is located) 2. remember: phosphorylase adds a Pi to a macromolecule to make a phosphorylated molecule 3. stops breaking off carbons when there are 4 glucose molecules left on a branch 4. the cofactor Pyridoxal phosphate is used in these reaction. It is a derivative of vitamin B6. You must memorize the structure of PLP. D. Glycogen Debranching Enzyme (see figure 15-4) 1. This enzyme has 2 activities: a. Transferase activity: when there are 4 glucose molecules left on the glycogen branch, glycogen debranching enzyme removes the 3 α14 glucose molecules and moves them to the main chain. b. Glucosidase activity: hydrolysis of the α16 linked glucose molecule. Because this is a hydrolysis, only glucose is released, NOT glucose-1-P E. Phosphoglucomutase (see figure 15-5) 1. catalyzes the reaction: G-1-P G-6-P 2. Phosphorylated serine side chain of the enzyme is involved in this step. V. Glycogen Synthesis: A. Glycogen synthase (see figure 15-8) 1. sequentially adds Glucose molecules in an α14 linkage bond 2. can only add glucose to the non-reducing end of the glycogen particle NHCH3OHO HOPOOOPyridoxal PhosphateMelody Daroogar OH: Monday 11 – 11:50am [email protected] At Roma Café B. Glycogen branching enzyme (see figure 15-9) 1. adds branches in an α16 linkage 2. it takes a group of α14 links and transfers them to a glucose molecule farther up the chain C. UDP-glucose and Glycogenin (see figure 15-11) 1. UDP-glucose is the activated precursor to glycogen synthesis 2. the tyrosine residue reacts with UDP-glu to yield a glucosylated tyr 3. UDP-glu keeps adding glu to the nascent chain until there are 8 glucose molecules. Then glycogen synthase takes over the adding of glucose molecules Questions from Week 4 1. Describe each step in glycolysis as a: a. Group transfer b. Red-ox c. Isomerization d. Breaking of C-C bond 2. How does the Schiff base that is formed in glycolysis help the reaction go forward? Draw the structure for your explanation. 3. In the breakdown of glycogen, you can get glucose-1-P and glucose. Which is more efficient for the cell to make? Why? What are the enzymes that make each of these
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