Lesson 10: Cellular Metabolism and Carbohydrates PDF

Biochemistry Lesson 10 Cellular Metabolism. Carbohydrates OUTLINE CATABOLISM • Glycolysis • Oxidative and Fermentative Metabolism • Krebs Cycle and Oxidative Phosphorylation • Catabolism of Polysaccharides • Glycogenolysis •Penthose phosphate pathway ANABOLISM • Gluconeogenesis • Glycogenesis G...

Biochemistry Lesson 10 Cellular Metabolism. Carbohydrates OUTLINE CATABOLISM • Glycolysis • Oxidative and Fermentative Metabolism • Krebs Cycle and Oxidative Phosphorylation • Catabolism of Polysaccharides • Glycogenolysis •Penthose phosphate pathway ANABOLISM • Gluconeogenesis • Glycogenesis GLUCOSE METABOLISM  GLUCOSE is the most abundant monosaccharide in nature  GLUCOSE is the main hydrocarbon fuel in most of the cells. And the only one for some specialized cells (ex. Neurons, erytrocytes, cornea…).  GLUCOSE is also the product of the photosynthesis that takes place in green plants because of Chlorophyll.  GLUCOSE can be stored in the form of GLYCOGEN (polysaccharide) in some cells, or can be degraded by OXIDATION  GLUCOSE can serve as a precursor of multiple biomolecules, coenzymes, nucleotides, carbon skeleton of amino acids, … GLUCOSE CATABOLISM Levels of metabolic complexity FATS POLYSACCHARIDES PROTEINS LEVEL 1 Fatty acids and glycerol Glucose and other sugars Amino acids LEVEL 2 ATP O2 ADP Oxidative Phosphorylation Acetyl- CoA e- CoA Citric acid cycle 2CO2 LEVEL 3 GLYCOLYSIS From the Greek “glykis” (sweet) y “lysis” (break)  Initial phase of hydrocarbon catabolism  Universal pathway in all living cells  In animals is the only pathway that yields ATP in the absence of oxygen and probably is the most ancient mechanism that exists to produce energy.  It was the first pathway to be know in detail  It is a complex sequence of 10 reactions enzymatically catalyzed, that take place in the cytosol of the cell.  Metabolic pathway by which the molecule of GLUCOSE splits in 2 molecules of PYRUVIC ACID and 2 ATP and 2 NADH are release . GLYCOLYSIS or EMBDEN-MEYERHOF ROUTE G’º = -16,7 kJ/mol G’º = 1,7 kJ/mol G’º = -14,2 kJ/mol ∆G’º = 23,8 kJ/mol GLYCOLYSIS or EMBDEN-MEYERHOF ROUTE ∆G’º = 7,5 kJ/mol In Duplicate G’º = 6,3 kJ/mol G’º = -18,5 kJ/mol G’º = 4,4 kJ/mol G’º = 7,5 kJ/mol G’º = -31,4 kJ/mol REGULATION of GLYCOLYSIS The rate of glucose oxidation is adjusted to meet the cell’s need for ATP The key regulatory enzyme is: PHOSPHOFRUCTOKINASE-1 (PFK-1) is the first enzyme that is common to the many possible starting points for glycolysis, and is therefore a key point of regulation. It is regulated by allosteric modulators. . Converts fructose 6-phosphate in 1,6-biphosphate High [ATP] High [AMP] Fructose-6phosphate High [citrate] PFK-1 Fructose 1,6biphosphate INHIBITORS ACTIVATORS EXIT To pyruvate This reaction has a free energy change of de –22,2 kJ/mol, highly exergonic, therefore it is irreversible Fructose 2,6biphosphate REGULATION of GLYCOLYSIS When glucose levels in blood are low, glucagon released by the pancreas, REDUCES indirectly the rate of glycolysis, by increasing glucose in blood. glucagon + Glycogen phosphatase Glucose Hexokinase glycogenolysis + Glucose 1 P Insulin + Phosphoglucomutase Glucose 6 phosphate When glucose levels in blood are high, insulin is released by the pancreas and STIMULATES the pathway, reducing glucose in blood. Synthesis of fructose-2,6bisP is a specific response to hormones. PHOSPHOFRUCTOKINASE-1 (PFK-1) is an allosteric enzyme PFK1 is a tetramer of four simple subunits of 36 kDa ATP is a negative effector and is also substrate SUMMARY of GLYCOLYSIS stages 10 steps, 2 phases 1.- Glucose is phosphorylated in its OH of carbon 6 to form glucose-6-phosphate 2.- Glucose-6-phosphate is rearranged (isomerization) to fructose-6 phosphate 3.- Fructose-6-phosphate is phosphorylated in carbon 1 to form 1,6 fructose-bis-phosphate 4.- Fructose 1,6 bis-phosphate is degraded in 2 molecules of 3 carbons: dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate 5.- Dihydroxyacetone-phosphate is isomerized to glyceraldehyde-3-phosphate 6.- Glyceraldehyde-3-phosphate is oxidized and phospharylated by inorganic phosphate and not ATP, forming 1,3-bisphosphoclycerate. The free energy of redox reaction is preserved in the form of phosphate bond energy. 7.- 1,3-bisphosphoglycerate transfers a phosphate group to ADP to form ATP and becomes 3-phosphoglycerate. This is the first reaction where energy is obtained by phosphorylation of substrate. 8.- 3-phosphoglycerate internally transfers a molecule of phosphate to carbon 2 to form 2-phosphoglycerate. 9.- 2-phosphoglycerate is dehydrated and converted to phosphoenolpyruvate 10.- Phosphoeneol pyruvate transfers a phosphate group to ADP, to obtain ATP by phosphorylation of substrate and yields pyruvate, the final product of the pathway. SUMMARY of GLYCOLYSIS Phase 1 Energy intake Phase 2 Energy Production SUMMARY of GLYCOLYSIS GLOBAL BALANCE Glucose + 2ATP + 2NAD+ +4ADP + 2Pi 2 pyruvate + 2ADP + 2NADH + 2H+ + 4ATP + 2H2O ATP NAD+ NADH glucose DEGRADATION 2 pyruvates CYTOSOL Net Result: Glucose: 2 pyruvate 2ADP: 2ATP 2NAD+: 2NADH destinations DEGRADATIVE DESTINATIONS OF PYRUVATE DESTINATIONS OF PYRUVATE 2 and 3: ANAEROBE PROCESSES FERMENTATIONS - in ABSENCE of O2 - in CYTOSOL Pyruvic acid obtained in glysolysis stays in the cytosol and undergoes fermentations, in this process more reduced organic compounds are formed (ethanol, lactic acid). GLUCOSE PYRUVATE CYTOSOL LACTATE / ETHANOL FERMENTATIONS Metabolic pathway used by ancient bacteria It is a less energetic process (2 ATP / glucose) ANAEROBIC BREAKDOWN PATHWAYS OF PYRUVATE 2 pathways for the anaerobic breakdown of pyruvate LACTIC FERMENTATION: When inadequate oxygen is present, for example, in a muscle cell undergoing vigorous contraction, the pyruvate produced by glycolysis is converted to lactate as shown. This reaction regenerates the NAD+ consumed in step 6 of glycolysis, but the whole pathway yields much less energy overall than complete oxidation. ALCOHOLIC FERMENTATION: In some organisms that can grow anaerobically, such as yeasts, pyruvate is converted via acetaldehyde into carbon dioxide and ethanol. Again, this pathway regenerates NAD+ from NADH, as required to enable glycolysis to continue. DESTINATIONS OF PYRUVATE 1. AEROBIC PROCESS: - In the PRESENCE of O2 - In the Mitochondria PYRUVATE Cytosol Oxidative decarboxylation mitochondrial matrix AcetylCoA + CO2 • In aerobic conditions, pyruvate formed in the cystosol is transported to the interior of mitochondria (mitochondrial matrix). • There, it is converted by oxidative decarboxylation to acetyl-CoA, and enters the Krebs cycle. Krebs Cycle Pyruvic acid Pyruvate dehydrogenase Acetyl-Coenzyme A ANAEROBIC AEROBIC OXIDATION Glucose FERMENTATION CYTOSOL 2ATP Pyruvate Acetyl-CoA ADP O2 ATP H2O CO2 32ATP MITOCHONDRIA Pyruvate +H2O + CO2 Glucose CYTOSOL Pyruvate Lactate Muscle contraction ethanol Anaerobic conditions yeast The complete oxidation of 1 molecule of GLUCOSE produces 32 ATP, while fermentation only 2 ATP COMPLETE BREAKDOWN of ACETYL-CoA In Krebs Cycle FATS POLYSACCHARIDES PROTEINS Fatty acids and glycerol Glucose and other sugars Amino acids ATP O2 ADP Oxidative phosphorylation Acetyl- CoA e- Krebs Cycle 2CO2 CoA Krebs Cycle Described by Hans Krebs in 1937. From the evolutive standpoint is more recent than glycolysis It is a metabolic cycle that consists of a series of chain reactions of: OxidationReduction, where molecules transform one another without running out. The only molecule that is metabolized is Acetyl-CoA. The Krebs cycle, also called the citric acid cycle, exists in all aerobic organisms. Requires oxygen to completely oxidize acetyl-CoA. Through the cycle the total oxidation of acetyl-CoA will be achieved to obtain CO2 and H2O. All this process takes place in the MITOCHONDRIAL MATRIX Krebs Cycle Its function is to OXIDIZE organics metabolites. The energy of oxidation is preserved as NADH and FADH2 . It accounts for about two-thirds of the total oxidation of carbon compounds in most cells. Obtaining Energy from an organic molecule occurs when it is oxidized (loses e- or H). Redox process, the organic molecule is oxidized, gives e- to a finalacceptor (reduced), usually a coenzyme (NAD+) It is the central nucleus of intermediate metabolism PROVIDING the cell with a huge variety of metabolic precursors: Amphibolic character: participates in catabolism as well as in anabolism. Many intermediates from the cycle can be used as a start point for many biosynthetic products. Anaplerotic reactions or pathways or replenishing of intermediates of the cycle. PATHWAYS THAT CONVERGE INTO THE KREBS CYCLE Krebs Cycle Phase 1: OXIDATION of 2 CARBONS (acetyl-CoA) to CO2 Step 1: introduction of 2 atoms of C in the form of acetyl-CoA Step 2: isomerization of citrate Step 3: generation of CO2 by a dehydrogenase link to NAD+ Step 4: generation of the second CO2 by multienzymatic complex Phase 2: REGENERATION of OXALOACETATE Step 5: phosphorylation at substrate level Step 6: dehydrogenation flavin dependent Step 7: hydration of double bond carbon-carbon Step 8: dehydrogenation that regenerates oxaloacetate Krebs Cycle Krebs Cycle Pyruvate OXIDATION CO2 Acetyl-CoA NADH2 For each turn of the cycle: 1 acetil-CoA = 2CO2 + 3 NADH + 1 FADH2 + GTP (≈ATP) + CoA OXIDATIVE PHOSPHORYLATION Krebs Cycle Simple overview NET RESULT The reaction of acetyl-CoA with oxaloacetate starts the cycle by producing citrate (citric acid). In each turn of the cycle, two molecules of CO2 are produced as waste products, plus three molecules of NADH, one molecule of GTP, and one molecule of FADH2. The number of carbon atoms in each intermediate is shown in a yellow box. Krebs Cycle Amphibolic character The Krebs cycle, besides being a degradative route, cycle intermediates are used as precursors in biosynthetic pathways. It is therefore considered an amphibolic pathway, catabolic and anabolic at the same time. ANAPLEROTIC REACTIONS OF KREBS CYCLE The Krebs cycle intermediates used for biosynthetic pathways must be replaced to maintain the flow through the cycle, anaplerotic routes. Main Anaplerotic Reactions Reactions that replenish the oxaloacetate: Enzyme:pyruvate carboxylase Pyruvate- Oxalacetate Enzyme: malate dehydrogenase Pyruvate - Malate Enzyme: Transaminases AspartateOxalacetate ANAPLEROTIC REACTIONS Krebs Cycle: Key regulatory enzymes REGULATION OF KREBS CYCLE Cycle rate is estimated in 100 turns/min, allowing the formation of 70 kg of ATP/day The rate of Krebs cycle depends on: 1.- amount of available oxaloacetate 2.- amount of ATP present in the cell 3.- mitochondrial relationship of relative concentrations of NAD + versus NADH 4.- Allosteric regulation of isocitrate dehydrogenase enzyme and αketoglutarate dehydrogenase complex X downregulation upregulation KEY CRITERIA TO REMEMBER A METABOLIC PATHWAY KEY CRITERIA TO REMEMBER A METABOLIC PATHWAY RESPIRATORY CHAIN AND OXIDATIVE PHOSPHORYLATION POLYSACCHARIDES Glucose and other sugars Phases 1 and 2 pyruvate GLYCOLYSIS LEVEL 1 LEVEL 2 Acetyl- CoA ATP O2 Oxidative phosphorylation NAD CoA ADP e- Citric acid cycle NADH 2CO2 LEVEL 3 RESPIRATORY CHAIN or ELECTRON TRANSPORT It consists of a chain of protein complexes (I-V) and coenzymes (coenzyme Q and cytochrome-C) located in the inner membrane of mitochondria, that accept and transfer electrons given by the coenzymes NADH and FADH2 from the Krebs cycle and glycolysis Intermembrane space H+ + e- H NADH NAD+ Mitochondrial matrix Respiratory chain: Internal membrane Mitochondria RESPIRATORY CHAIN or ELECTRON TRANSPORT In Mitochondria Electrons pass from high to lower energetic levels: Electron flow is in favor of gradient. From a substance with a negative redox potential to another of positive redox potential. Internal membrane is impermeable to protons: H+ are pumped from the matrix to the intermembrane space where they accumulate. Intermembrane space Matrix pH is ~ 8, while in intermembrane space is ~ 7 matrix Both the pH gradient and electrical potential drive the flow of protons back into the mitochondrial matrix Through a protein channel: ATP-synthase RESPIRATORY CHAIN AND OXIDATIVE PHOSPHORYLATION http://www.wiley.com/college/pratt/0471393878/student/animations/oxidative_phospho rylation/index.html RESPIRATORY CHAIN or ELECTRON TRANSPORT Electron Transport Complexes Complex I NADH-Ubiquinone reductase Complex II Succinate-Ubiquinone reductase Electrons of FADH2, transferred through complexes II, III and IV Complex III Ubiquinone-cytochrome C reductase Complex IV Cytochrome C oxidase Electrons of NADH +H+ create a major electrochemical gradient OXIDATIVE PHOSPHORYLATION Chemiosmotic theory (Mitchell): Mechanism in which a gradient of hydrogen ions (a pH gradient) across a membrane is used to drive an energy-requiring process, such as ATP production. Oxidative phosphorylation takes place in the inner membrane of mitochondria, and catalyzes several redox reactions, where oxygen is the final acceptor of electrons and phosphorylation of ADP to produce ATP happens. ATP-synthase, located at the inner membrane of mitochondria, uses the proton gradient (proton motive force) to convert the major part of energy of NADH to generate ATP from ADP. RESPIRATORY CHAIN and OXIDATIVE PHOSPHORYLATION Respiratory chain Mitochondrial matrix  NADH, FADH Inner membrane  Electron transport chain: Protein complexes and coenzymes.  ATP synthase (complex V, complex F0F1) Intermembrane space  High concentration of H+ Chemiosmotic Theory Mitochondrial Cristae complex F0F1 or ATP synthase ATP synthase View from above • For each NADH, 10 protons are pumped to the intermembrane space. • For each FADH2 only 6 protons are pumped. • For every 3 protons that go through ATP synthase, 1 ATP molecule is generated. Thus, each NADH produces 3 ATP (or 2,5 ATP); each FADH2 produces 2 ATP (or 1,5 ATP). To take into consideration  NADH and FADH2 (reduced coenzyme) are electron donor molecules to the electron transport chain, since they were "charged" during the citric acid cycle. When they are oxidized release electrons (e-) and protons.  The transport chain molecules are arranged according to their redox potential: low to a greater tendency to capture e-, so at the end of the chain requires a very avid acceptor of e-: oxygen  The generated electrons are transported through the electronic transport of the respiratory chain, including several enzyme complexes, coenzyme Q and cytochrome c.  The protons released into the matrix will be pumped into the intermembrane space against the gradient, generating a proton gradient (high in the intermembrane space and low in the matrix) The transport of e- by the transport chain generates energy to pump protons (in three points) from the mitochondrial matrix to the intermembrane space against the gradient. Oxygen is required as the final acceptor of e- in the transport chain Oxygen binds to the e- and protons to form water To do in class: COMPLETE THE SCHEME AND CALCULATE THE ENERGETIC OUTPUT OF THE TOTAL OXIDATION OF A MOLECULE OF GLUCOSE FINAL BALANCE OF GLUCOSE OXIDATION IN CELLULAR RESPIRATION Assuming 1 NADH = 2,5 ATP 1 FADH2= 1,5 ATP FINAL BALANCE OF GLUCOSE OXIDATION IN CELLULAR RESPIRATION Assuming 1 NADH = 3 ATP 1 FADH2= 2 ATP 38 ATP POLYSACCHARIDE CATABOLISM In animal metabolism there are two main sources of glucose from polysaccharides: - The digestion of dietary polysaccharides (mainly vegetable starch and glycogen of the meat) - The mobilization of glycogen stocks DEGRADATION OF STARCH DEGRADATION OF GLYCOGEN MOBILIZATION OF GLYCOGEN GLYCOGEN Branched polysaccharide present in animals cells, certain protozoans and algae. A very efficient way to store glucose, the main molecule that provides energy in animal cells. In humans is stored in the liver in the form of granules, and in the skeleton muscle. It is a soluble molecule. In cells is stored in cytoplasmatic vesicles to be used in glycolysis. Free inside the cell could cause osmotic problems BREAKDOWN OF GLYCOSILIC BOND by HYDROLYSIS OR PHOSPHOROLYSIS Polysaccharides from the diet are degraded by Hydrolysis to monosaccharides GLUCOSE Hydrolysis of glycosilic bonds OH O O O H2O hydrolysis + OH OH OH Intracellular deposits of glycogen are mobilized by PHOSPHOROLYSIS BREAKDOWN OF GLYCOGEN GLYCOGENOLYSIS: Breakdown of glycogen to glucose 6-phosphate Catalyzed by three enzymes: 1. Glycogen phosphorylase kinase (GPK) 2.- Glycogen debranching enzyme 3.- Phosphoglucomutase 1. Glycogen phosphorylase kinase (GPK) : Catalyzes the phosphorolytic cleavage, which consists of the sequential output of traces of glucose from the nonreducing end, according to the reaction (glucose)n + Pi <---------------> (glucose)n-1 + glucose-1-P 2. The glycogen debranching enzyme has two activities: α(1-4) glycosyl transferase that transfers each unit of the nonreducing end trisaccharide, and (1-6) glycosidase that hydrolyzes the remaining glucose unit in α(1-6). 3. Phosphoglucomutase: It transforms glucose 1-P in glucose 6-P glucose-1-P <---------------> glucose-6-P GLYCOGENOLYSIS: Breakdown of glycogen to glucose 6-phosphate 1.Glycogen phosphorylase kinase (GPK) 2.The glycogen debranching enzyme: has two activities: α(14) glycosyl transferase that transfers each unit of the nonreducing end trisaccharide, and (16) glycosidase that hydrolyzes the remaining glucose unit in α(1-6). GLYCOGENOLYSIS: Breakdown of glycogen to glucose 6-phosphate 3. The glucose 6phosphate is an intermediate metabolite that participates in different metabolic pathways. GLYCOGENOLYSIS is regulated by glucagon and epinephrine REGULATION: Stimulated by a rise in cAMP following epinephrine OR glucagon stimulation of cells and, in muscle, by a rise in Ca2+ following neuronal stimulation STARCH Polysaccharide for storage in plants Present in 2 forms: - Amylose, a type of unbranched starch - Amylopectin a type of branched starch, similar to glycogen Both are rapidly hydrolysed by amylase enzyme secreted by salivary glands and pancreas. DEGRADATION OF STARCH HYDROLYSIS amylase 2 glucoses maltase maltotriose dextrin 2 glucoses maltotriose 3 glucoses dextrinase GLUCOSE amylose amylopectin maltose GLUCOSE ANABOLISM • GLUCONEOGENESIS: SYNTHESIS OF GLUCOSE (mainly in hepatocytes) from non-carbohydrate elements (aa + lactate) • GLYCOGENESIS: GENERATION of GLYCOGEN by joining glucose molecules GLUCONEOGENESIS • Glucose synthesis in non-autotrophic cells • Very important pathway as it allows the supply of glucose when blood levels are not adequate • Synthesis from pyruvate, with the expense of ATP, NADH + , H + • Synthesis from non-carbohydrate precursors: aa, lactate, glycerol, Krebs cycle intermediates • It only takes place in the liver and kidney cortex • It takes place in the cytosol, except the first step, which occurs in mitochondria GLUCONEOGENESIS Biological significance  Certain tissues need a continuous supply of glucose: brain and erythrocytes  Direct glucose stocks are only sufficient to cover the needs of one day; longer periods of fasting involve the need for more glucose Gluconeogenesis: synthesis of glucose from: - Lactate: active skeletal muscle Glycerol: triglyceride hydrolysis in adipose cells - Amino acids: proteins of skeletal muscle or degradation of dietary protein CORI CYCLE Coupling of two metabolic pathways (glycolysis and gluconeogenesis) in two different organs (muscle and liver) Allows muscle cells to have energy at all times The muscle gets ATP in the glycolysis; in anaerobic conditions glucose is degraded to pyruvate and this is reduced to lactate. Lactate is exported to the blood stream and is taken up by the liver. The liver synthesizes new glucose from lactate through the gluconeogenic pathway GLYCOGENESIS Synthesis of glycogen after ingestion of a carbohydrate-rich diet Glucose is stored as glycogen in muscle and liver The Liver is the main storage organ of glycogen, due to the presence of glucokinase For the biosynthesis of glycogen is required: 1) two enzymes: glycogen synthase and branching enzyme 2) UDP-glucose molecules 3) a pre-existing glycogen chain or primer UDPglucosepyrophos phorylase GLYCOGEN Glycogen synthesis from glucose is called Glycogenogenesis or Glycogenesis (glucose)n + UDP-glucose (glucose)n+1 + UDP Glycogen synthase ATP ADP Glucose GLYCOGENESIS UDP-glucose, the activated intermediate in glycogen synthesis, is formed from glucose 1phosphate and UTP. Synthesis is primed by glycogenin, an autoglycosylating protein that contains a covalently attached oligosaccharide unit on a specific tyrosine residue. A branching enzyme converts some of the α-1,4 linkages into α-1,6 linkages to increase the number of ends so that glycogen can be made and degraded more rapidly. Glycogen synthase catalyzes the transfer of glucose from UDPglucose to the C-4 hydroxyl group of a terminal residue in the growing glycogen molecule. Branching is important because it increases the solubility of glycogen. Furthermore, branching creates a large number of terminal residues, the sites of action of glycogen phosphorylase and synthase. Thus, branching increases the rate of glycogen synthesis and degradation. GLYCOGENESIS REGULATION GLYCOGEN DEGRADATION GLYCOGEN SYNTHESIS Inactive forms are shown in red, and active ones in green. Glycogen metabolism is regulated, in part, by hormone-triggered cyclic AMP cascades. The sequence of reactions leading to the activation of protein kinase A is the same in the regulation of glycogen degradation and synthesis. Phosphorylase kinase also inactivates glycogen synthase. HORMONAL REGULATION OF GLYCOGEN METABOLISM PENTOSE PHOSPHATE PATHWAY It is a secondary route for the degradation of glucose, that does not aim at the formation of ATP, but to obtain non-hexose monosaccharides or trioses: pentose-phosphate, necessary for the biosynthesis of nucleic acid and NADPH The pentose phosphate pathway meets the need of all organisms for a source of NADPH to use in reductive biosynthesis This pathway consists of two phases: the oxidative generation of NADPH and the nonoxidative interconversion of sugars. It takes place in the cytosol. BASIC CONCEPTS METABOLIC ROUTES • Glycolysis: type of metabolic pathway, key regulatory enzymes, hormonal regulation, energetic balance, cellular location, • Oxidative and Fermentative Metabolism: differences and similarities, cellular location, regulation, energetic output. • Krebs Cycle: amphibolic and anaplerotic character, key regulatory enzymes, cellular location, energetic balance, regulation. Central role of Krebs cycle • Electronic chain and Oxidative Phosphorylation: purpose, cellular location, proteins implicated, chemiosmotic theory. Importance. • Catabolism of Polysaccharides: hydrolysis and phosphorolysis • Glycogenolysis: type of metabolic pathway, key regulatory enzymes, cellular location, purpose • Penthose phosphate pathway: type of metabolic pathway, cellular location, purpose. • Gluconeogenesis: type of metabolic pathway, purpose, cellular location, • Cori cycle: purpose and biological importance. Metabolic pathways implicated • Glycogenogenesis: type of metabolic pathway, key regulatory enzymes, cellular location, purposes and biological importance. METABOLITES AND ENERGETIC MOLECULES: Glucose, Fructose 1-6biP, pyruvate, acetyl coA, oxalacetate, citrate and other metabolites of Krebs cycle. NAD+, NADH, FAD+, FADH2, ATP, ADP