BMS100 BCH1 Metabolism Overview Student PDF

Metabolism Overview Dr. Heisel Dr Fraser BMS100 Objectives Define and contrast anabolism and catabolism List examples of direct and indirect cellular energy Provide the substrate(s), product(s), purpose and cellular location of the following anabolic pathways: Gluconeogenesis, glycogenesis, fatty ac...

Metabolism Overview Dr. Heisel Dr Fraser BMS100 Objectives Define and contrast anabolism and catabolism List examples of direct and indirect cellular energy Provide the substrate(s), product(s), purpose and cellular location of the following anabolic pathways: Gluconeogenesis, glycogenesis, fatty acid synthesis, lipogenesis, ketogenesis, pentose phosphate shunt Objectives Provide the substrate(s), product(s), purpose and cellular location of the following catabolic pathways: Glycolysis, glycogenolysis, beta oxidation, lipolysis, ketolysis, citric acid cycle Differentiate between glycolysis under aerobic and anaerobic conditions Describe the overall set-up and working of the ETC Metabolism Anabolism Metabolic pathways that build molecules from smaller subunits – requires energy Energy Catabolism Metabolic pathways that breakdown larger molecules into smaller subunits – releases energy Energy Review: ATP for Energy http://commons.wikimedia.org/wiki/File:ATP-3D-vdW.png Review: ATP ATP structure Note the three parts of the nucleotide structure – what are they? Note the high energy phosphoanhydride bonds Burning of fuels ADP + Pi Biological Work ATP NH2 C N HC O O O O P O P O P O C H2 O O O H H HO N C N C N O H H HO CH Energy Production Forms of cellular energy ATP = direct energy NADH and FADH2 = indirect energy Need to go to ETC to make ATP Next: Overview of Anabolic and Catabolic Pathways A closer look at sugars and fats ANABOLIC PATHWAYS Purpose Location Gluconeogenesis Gluconeogenesis Makes glucose from precursor molecules Mitochondria and cytosol Glycogenesis Glycogenesis Makes glycogen to store glucose Cytosol Fatty acid synthesis Fatty Acid Synthesis Makes fatty acids from acetyl CoA Cytosol Lipogenesis/ triglyceride Lipogenesis synthesis Adds fatty acids to a glycerol backbone to make triglyceride lipids Cytosol Ketogenesis Ketogenesis Makes ketone bodies from acetyl CoA Mitochondria Pentose Phosphate Shunt Pentose Phosphate (PPS) Shunts glucose into the creation of various 5-carbon sugars and NADPH Cytosol Shunt CATABOLIC PATHWAYS Glycogenolysis Glycogenolysis Purpose Location Breakdown of glycogen to release glucose. Glucose can then enter glycolysis to produce energy. Cytosol Glycolysis Glycolysis Breakdown of glucose to pyruvate to produce Cytosol energy (NADH, ATP). After glycolysis, pyruvate can be converted to acetyl CoA to enter the CAC to produce more energy. Beta oxidation Beta Breakdown of fatty acyls to acetyl CoA to produce energy (NADH, FADH2). Acetyl CoA can enter the CAC to produce more energy. Mitochondria Ketolysis/ketone Ketolysis body oxidation Breakdown of ketone bodies to acetyl CoA. Acetyl CoA can enter the CAC to produce more energy. Mitochondria Krebs Cycle/Citric Citric Acid Acid Cycle (CAC) Breakdown of citrate (made from acetyl CoA and oxaloacetate) to produce energy (NADH, FADH2, ATP). Mitochondria oxidation Cycle Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones *NADH, FADH2 Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA Glucose for energy Glycolysis Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA Glycolysis Cytosol Glucose Glucose 6-P Conversion of glucose into two pyruvate in the cytosol ATP NADH ATP and NADH produced Pyruvate can then be converted to acetylCoA Creates more NADH Can enter CAC Why does conversion of pyruvate to acetyl CoA only happen under aerobic conditions? Pyruvate Mitochondia Pyruvate NADH Acetyl CoA NADH FADH2 ATP CAC Anaerobic Glycolysis When there is a lack of oxygen, pyruvate converts to lactate rather than ? Purpose Cytosol Glucose Glucose 6-P NADH + H+ NAD+ ADP + Pi ATP Regenerates NAD+ How is this helpful in terms of energy production? Lactate Pyruvate NAD+ Glucose for energy: How do we get it? Besides indulging in chocolate, option 1 = make it from scratch Gluconeogenesis Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA Gluconeogenesis Cytosol Glucose Glucose 6-P Liver is a main site of GNG Helps make glucose to send to other tissues when blood sugar is low Glycerol Pyruvate Lactate oxaloacetate Substrates include: Certain amino acids (“glucogenic” aa’s) Lactate Mitochondia Pyruvate oxaloacetate Glycerol Various aa’s Glucose for energy: How do we get it? Option 2: Breakdown glycogen Glycogenolysis Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA Glycogenolysis Liver and muscle breakdown glycogen for different reasons Liver Releases glucose to raise blood sugars levels when they are low Muscles Why do you think? Glucose – What do we do with it if have more than we need? Store it Glycogenesis Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA Glycogenesis This is an anabolic process – where is the energy input? Glycogen Cytosol UDP-glucose ATP Not recuperated via glycolysis UTP What is UTP? Breaking P off of UTP is similar to breaking P off of ATP UTP Glucose ATP Glucose 6-P Glucose – What else can we do with it? Send it into the pentose phosphate shunt Makes: NADPH – used for fatty acid synthesis, antioxidation 5-C sugars - such as ribose -5- P for nucleotide synthesis Can feed sugars back into glycolysis (“shunt”) if needed Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA Breakdown of fatty acids for energy Beta oxidation What type of energy is produced? What are the fats broken down into? What happens to this molecule next if you want more energy? Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA Making fatty acids Excess glucose can divert to make fatty acids What is one connection between excess glucose and fatty acid synthesis? NADPH Glucose Glucose 6-P 5-C sugars Fatty Acids Pyruvate Acetyl CoA Lipogenesis If you don’t need your fatty acids for energy, how do you store them for later retrieval and use? Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA Lipolysis Releases fatty acids from triglycerides How does this contribute to energy production? Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA Triglycerides for energy Compared to glycogen, TG’s take up less space Based on their structures, why do you think this is? This is one reason they can store more energy https://commons.wikimedia.org/wiki/File:Glycogen_chain.png https://commons.wikimedia.org/wiki/File:220_Triglycerides-01.jpg Ketones Ketogenesis The liver can make ketone bodies from acetyl CoA These ketone bodies can then be used by other tissues (such as cardiac muscle, smooth muscle, brain) when energy is needed Ketolysis The breakdown of ketone bodies to release acetyl CoA How does this help with energy production? Note: The liver only makes ketone bodies, it cannot use them itself Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones *NADH, FADH2 Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA Citric Acid Cycle Any cycle that can lead to the production of acetyl CoA can feed into CAC to make more energy What 3 catabolic pathways can feed into CAC? Cytosol Glycogen ATP Glucose 6-P Glucose NADPH ATP Pyruvate Glycerol PentoseP-Sugars ATP *NADH Triglycerides Fatty AcylCoA *NADH Fatty Acids Oxaloacetate *NADH Pyruvate ATP AcetylCoA Oxaloacetate Mitochondria CO2 *NADH, FADH2 O2 *NADH, FADH2 Citrate Citric Acid Cycle Ketones *NADH, FADH2 Fatty AcylCoA ATP Electron Transport Chain ATP ATP H2O Acetyl CoA ETC Found in the inner mitochondrial membrane Takes electrons from NADH and FADH2 Passes them down a chain of electron carriers with increasing electron affinity Eventually donates them to oxygen to make water Energy from electron movement used to pump H+ into the intermembrane space Creates an H+ gradient that is used to drive the production of ATP ETC Cytosol Outer Membrane InterMembrane Space Inner Membrane e- I H+ NADH Matrix H+ Q II e- H+ e- FADH2 H+ III c e- H+ H+ IV H+ H+ 4 e- + 4H+ + O2 2H2O ATP Synthase I, II, III, IV, Q and c = parts of the ETC that accept/donate e Movement of e- down ETC results in pumping of H+ into intermembrane space H+ move back out via ATP Synthase, which makes ATP H+ ATP