Metabolism JL Spadano Gasbarro PhD LDN Northeastern University HSCI 1105 Overview Energy metabolism basics Extracting energy from CHO Fat Protein Brief overview of biosynthesis Feast and Famine Energy Metabolism Def Reactions by which the body obtains and expends energy from food Whitney Rolfes 13th ed Our body cells obtain their energy from chemical energy held in the molecular bonds of CHO lipids and protein as well as alcohol Photosynthesis Converts radiant energy from sun into chemical energy within the bonds that hold atoms together specifically between the C and H atoms Metabolic Reactions Catabolic vs Anabolic Role of Enzymes Cofactors Coenzymes B vitamins Coupling Reactions A pair of chemical rxns in which E released from breakdown of one compound is used to create a bond in the formation of another compound Often energy captured and transferred by go between molecules such as ATP Body uses ATP to transfer the energy released from the breakdown of energy yielding nutrients to power its anabolic reactions Conversion is not very efficient Production of ATP directly related to energy needs Insel et al Nutrition 5th ed Breakdown and Release of Energy Shared catabolic pathways Citric Acid Cyle Electron Transport Chain Electron Acceptors Oxidation results in release of high energy electrons NAD Nicotinamide adenine dinucleotide Accepts 2 electrons and 2 H ions to form NADH H FAD Flavin adenine dinucleotide Forms FADH2 Extracting Energy from CHO From 4 main pathways Glycolysis Conversion of pyruvate to acetyl CoA Citric Acid Cycle Electron Transport Chain Step 1 Glycolysis An anaerobic process Occurs in the cytosol Requires 2 molecules of ATP Each glucose molecule yields 2 pyruvate molecules Net yield of 2 ATP and 2 NADH H Step 2 Conversion of Pyruvate to Acetyl CoA If cells need energy and O2 is available Aerobic rxn Occurs in cell s mitochondria Yields 1 NADH H Derived from B vitamin pantothenic acid Thiamin is part of coenzyme TTP When oxygen is in short supply such as with rapidly contracting muscle pyruvate alternatively forms lactic acid Anaerobic Lactic acid Alternative fuel used by muscle cells Converted back to glucose by liver cells can then return to muscles Cori cycle Step 3a Citric Acid Cycle TCA Cycle Krebs Cycle Set of rxns that proceed on a circular pathway in the mitochondria Begins with Acetyl CoA binding with Oxaloacetate Each AcetylCoA or turn of the citric acid cycle yields recall 2 AcetylCoA per glucose CO2 3 NADH FADH2 electron transport chain 3 NAD FAD used GTP ATP Step 4 Electron Transport Chain Located in the inner mitochondrial membrane Aerobic process Main site of ATP production Formation of ATP coupled with the flow of electrons across the electron transport chain is called oxidative phosphorylation Without oxygen to accept the energy depleted electrons the transport of electrons down the chain would stop halting ATP production Complete Oxidation of Glucose End Products CO2 Pyruvate to Acetyl CoA Citric acid cycle H2O Electron transport chain ATP 2 ATP from glycolysis 1 GTP from citric acid cycle remaining from electron transport chain Total 30 32 ATP Depends on cytosolic NADH from glycolysis NADH yields 2 5 ATP FADH2 yields 1 5 ATP Figure 8 13 Insel et al Nutrition 5th ed Extracting Energy From Fat Glycerol Pyruvate or Glucose in liver Only 5 of fat s weight FAs Acetyl CoA FA activated by CoA Ferried into the mitochondria by carnitine Beta oxidation removes 2 C at a time from the beta end End product Acetyl CoA NADH H FADH2 Stearic Acid C18 16C yields 8 Acetyl CoA 7 FADH2 7 NADH H Figure 7 11 Whitney and Rolfes Understanding Nutrition 13th ed Figure 8 15 Insel et al Nutrition 5th ed Fat Burns In A Flame Of CHO Need oxaloacetate for acetyl CoA to enter citric acid cycle When oxaloacetate is depleted fat can not be fully oxidized Acetyl CoA rerouted to form ketone bodies in process called ketogenesis Ketone Bodies Body makes and uses small amts all the time When production exceeds excretion through urine or exhalation ketone bodies accumulate in the blood ketosis normal ketosis brief fast hyperketonemia of diabetic ketoacidosis Given time body can adapt to a high fat low CHO diet e g Inuit peoples and avoid ketosis Extracting Energy from Protein Takes priority during starvation or when CHO not available First step Deamination Removal of amino grp and ultimately excretion as urea Fate of remaining carbon skeleton determined by unique R group Glucogenic aa Pyruvate energy or glucose Ketogenic aa Acetyl CoA energy or FA synthesis Some aa enter TCA cycle directly energy or glucose Yields comparatively little ATP Figure C 3 Whitney and Rolfes Nutrition 13th ed Biosynthesis and Storage Glucose Gluconeogenesis Occurs in liver 90 and kidneys Not reversal of glycolysis although share some common reactions Sources pyruvate lactate gluconeogenic aa glycerol Glycogen liver and muscle Biosynthesis and Storage Fat Lipogenesis Acetyl CoA most important ingredient Precursors Ketogenic aa FAs Alcohol Assembles 2 C Acetyl CoA into FA chains but NOT the reversal of beta oxidation Different rxns Different location cytosol for FA synthesis and endoplasmic reticulum for triglyceride synthesis into body fat Requires energy Biosynthesis and Storage Protein Synthesis of non essential aa Transamination Transfers the amino grp from one aa to form a different aa C skeletons provided from pyruvate and intermediates of glycolysis and citric acid cycle One group of enzymes involved in transamination called aminotransferases are derived from the B vitamin pyridoxine B6 Hormonal regulators of metabolism Insulin CHO use and storage as glycogen Fat storage AA uptake by cells and protein synthesis Glucagon Stimulates breakdown of liver glycogen Cortisol Promotes breakdown of aa for gluconeogenesis and increases activity of gluconeogenic enzymes Epinephrine Promotes conversion of glycogen to glucose in muscle Times of plenty Rapid secretion of insulin CHO Refill liver and muscle glycogen store Excess CHO maximizes oxidation of CHO minimizes fat oxidation body fat storage Fat predominantly fat storage requires only a few steps and costs little energy Protein Refills aa pool Some increases in protein oxidation Excess deaminated body fat storage Fasting and Starvation First priority to preserve glucose depending tissue Brain cells RBCs and rest of CNS Leads to shift to FA and ketone bodies as primary fuel for body Second priority to maintain muscle mass Stages of Fasting Starvation