CATABOLISM AND ANABOLISM METABOLISM ENERGY TRANSFER ATP MOLECULE & ENERGY OXIDATION AND REDUCTION
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1 METABOLISM Functions of food source of energy essential nutrients stored for future use Metabolism is all the chemical reactions of the body some reactions produce the energy which is stored in that other reactions consume all molecules will eventually be broken down and recycled or excreted from the body CATABOLISM AND ANABOLISM Catabolic reactions breakdown complex organic compounds providing energy (exergonic) glycolysis, Krebs cycle and electron transport Anabolic reactions synthesize complex molecules from small molecules requiring energy (endergonic) Exchange of energy requires use of (adenosine triphosphate) molecule MOLECULE & ENERGY Each cell has about 1 billion molecules that last for less than one minute Over half of the energy released from is converted to heat 6-3 ENERGY TRANSFER Energy is found in the bonds between atoms Oxidation is a decrease in the energy content of a molecule Reduction is the increase in the energy content of a molecule Oxidation-reduction reactions are always coupled within the body whenever a substance is oxidized, another is almost simultaneously reduced. 6-4 OXIDATION AND REDUCTION 6-5 Biological oxidation involves the loss of electron and a proton (hydrogen atom) dehydrogenation reactions require coenzymes to transfer hydrogen atoms to another compound common coenzymes of fliving i cells that tcarry H+ NAD (nicotinamide adenine dinucleotide ) NADP (nicotinamide adenine dinucleotide phosphate ) FAD (flavin adenine dinucleotide ) NAD + + H Biological reduction is the addition of electron and a proton (hydrogen atom) to a molecule increase in potential energy of the molecule 1
2 CARBOHYDRATE METABOLISM Dietary carbohydrate burned as fuel within hours of absorption All oxidative carbohydrate consumption is essentially a matter of glucose catabolism C 6 H 1 O 6 + 6O 6CO + 6H O+ energy Function of this reaction is to transfers energy from glucose to not to produce carbon dioxide and water 6-7 GLUCOSE CATABOLISM catabolism a series of small steps, each controlled by a separate enzyme, in which energy is released in small manageable amounts, and as much as possible, is transferred to and the rest is released as heat Three major pathways of glucose catabolism glycolysis glucose (6C) split into pyruvic molecules (3C) anaerobic fermentation occurs in the absence of oxygen reduces pyruvic to lactic aerobic respiration occurs in the presence of oxygen completely oxidizes pyruvic to CO and H O 6-8 MECHANISMS OF GENERATION Phosphorylation is bond attaching 3rd phosphate group contains stored energy Mechanisms of phosphorylation within animals substrate-level phosphorylation in cytosol oxidative phosphorylation in mitochondria in chlorophyll-containing plants or bacteria photophosphorylation. OVERVIEW OF PRODUCTION Key Carbon atoms Phosphate groups 1 Phosphorylation ADP 6-phosphate Fat Fructose 6-phosphate Priming ADP Fructose 1,6-diphosphate 3 Cleavage PGAL NAD + P i NADH + H + 4 Oxidation NADH + H + NAD + ADP H O 5 Dephosphorylation ADP pyruvic 6-9 lactic Anaerobic fermentation Aerobic respiration 6-10 STEPS OF GLYCOLYSIS (1) Phosphorylation glucose enters cell has phosphate added - used maintains favorable concentration gradient, prevents glucose from leaving cell Priming isomerization occurs phosphorylation further activates molecule - used Cleavage molecule split into threecarbon molecules Oxidation removes H + STEPS OF GLYCOLYSIS () NAD + +H NADH Dephosphorylation transfers phosphate groups to ADP to form 4 s produced ( used) for a net gain of produces pyruvic Animation
3 STEPS OF GLYCOLYSIS 4 are produced but were consumed to initiate glycolysis, so net gain is per glucose molecule Some energy originally in the glucose is contained in the, some in the NADH, some is lost as heat, but most of the energy remains in the pyruvic End-products of glycolysis are: pyruvic + NADH + ANAEROBIC FERMENTATION Fate of pyruvic depends on oxygen availability In an exercising muscle, demand for > oxygen supply; produced by glycolysis glycolysis can not continue without supply of NAD + NADH reduces pyruvic to lactic, restoring NAD + Lactic travels to liver to be oxidized back to pyruvic when O is available (oxygen debt) then stored as glycogen or released as glucose Fermentation is inefficient, not favored by brain or heart ANAEROBIC FERMENTATION Lactic leaves the cells that generate it enter bloodstream and transported to the liver when oxygen becomes available the liver oxidized it back to pyruvic oxygen is part of the oxygen debt created by exercising muscle Liver can also convert lactic back to G6P and can: polymerize it to form gy glycogen g for storage remove phosphate group and release free glucose into the blood Drawbacks of anaerobic fermentation wasteful, because most of the energy of glucose is still in the lactic and has contributed no useful work lactic is toxic and contributes to muscle fatigue Skeletal muscle is relatively tolerant of anaerobic fermentation, cardiac muscle less so the brain employs no anaerobic fermentation 6-15 AEROBIC RESPIRATION Most generated in mitochondria, which requires oxygen as final electron acceptor In the presence of oxygen, pyruvic enters the mitochondria and is oxidized by aerobic respiration Occurs in two principal steps: matrix reactions their controlling enzymes are in the fluid of the mitochondrial matrix membrane reactions - whose controlling enzymes are bound to the membranes of the mitochondrial cristae 6-16 MITOCHONDRIAL MATRIX REACTIONS Pyruvic (C 3) 6 CO NAD + 7 Acetyl group (C ) 8 Acetyl-Co A Coenzyme A H O 9 Citric (C 6) Oxaloacetic 10 H O (C Citric 6) 18 NAD + cycle H NAD O CO 17 (C 5) H O NAD 13 + Occurs in mitochondrial matrix FADH CO FAD P i 15 GTP GDP ADP Pyruvic oxidation Citric (Krebs) Cycle 6-17 MITOCHONDRIAL MATRIX REACTIONS Three steps prepare pyruvic to enter citric cycle decarboxylation so that a 3-carbon compound becomes a -carbon compound CO removed from pyruvic convert that to an acetyl group (acetic ) NAD + removes hydrogen atoms from the C compound acetyl group binds to coenzyme A results in acetyl-coenzyme A (acetyl- CoA)
4 MITOCHONDRIAL MATRIX REACTIONS Citric Acid Cycle acetyl-co A (a C compound) combines with a C 4 to form a C 6 compound (citric )-- start of cycle hydrogen atoms are removed and accepted by NAD + another CO is removed and the substrate becomes a five-carbon chain previous step repeated removing another free CO leaving a four-carbon chain two hydrogen atoms are removed and accepted by the coenzyme FAD two final hydrogen atoms are removed and transferred to NAD+ reaction generates oxaloacetic, which starts the cycle again 6-19 SUMMARY OF MATRIX REACTIONS pyruvate + 6H O 6CO ADP + P i 8 NAD H 8 NADH + 8 H + FAD + H FADH Carbon atoms of glucose have all been carried away as CO and exhaled Energy lost as heat, stored in, 8 reduced NADH, FADH molecules of the matrix reactions and NADH from glycolysis Citric cycle is a source of substances for synthesis of fats and nonessential amino s 6-1 MEMBRANE REACTIONS Membrane reactions have two purposes: to further oxidize NADH and FADH and transfer their energy to to regenerate NAD + and FAD and make them available again to earlier reaction steps Mitochondrial electron-transport chain series of compounds that carry out this series of membrane reactions most bound to the inner mitochondrial membrane arranged in a precise order that enables each one to receive a pair of electrons from the member on the left side of it. pass electrons to member on the other side 6- ELECTRON TRANSPORT CHAIN 50 NAD + Relative free energy (kcal/mole) FMN Fe-S FADH Enzyme complex 1 FAD CoQ Cyt b Fe-S Cyt c1 Enzyme complex Cyt c Cu Figure Cyt a Cyt a ½ O + H Reaction progress Enzyme complex 3 H O 6-4 4
5 CHEMIOSMOTIC MECHANISM Electron transport chain energy fuels respiratory enzyme complexes pump protons from matrix into space between inner and outer mitochondrial membranes creates steep electrochemical gradient for H + across inner mitochondrial membrane Inner membrane is permeable to H + at channel proteins called synthase Chemiosmotic mechanism - H + current rushing back through these synthase channels drives synthesis (ANIMATION) 6-5 OVERVIEW OF PRODUCTION NADH releases an electron pair to electron transport system and H + to prime pumps enough energy to synthesize 3 FADH releases its electron pairs further along electron-transport system enough energy to synthesize Complete aerobic oxidation of glucose to CO and H O produces efficiency rating of 40% - 60% is lost as heat GENERATED BY OXIDATION OF GLUCOSE Glycolysis (net) NADH + H + pyruvate Cytosol Mitochondria NADH + H + 6 NADH + 6 H + Citric cycle FADH Electron-transport chain CO Total O H O GLYCOGEN METABOLISM is quickly used after it is formed it is an energy transfer molecule, not an energy storage molecule converts the extra glucose to other compounds better suited for energy storage (glycogen and fat) esis - synthesis of glycogen stimulated by insulin chains glucose monomers together olysis hydrolysis of glycogen releases glucose between meals stimulated by glucagon and epinephrine only liver cells can release glucose back into blood Gluconeogenesis - synthesis of glucose from noncarbohydrates, such as glycerol and amino s occurs chiefly in the liver and later, kidneys if necessary
6 GLUCOSE STORAGE AND USE 6-phosphatase (in liver, kidney, and intestinal cells) Key esis olysis Blood glucose 6-phosphate Glycolysis Hexokinase (in all cells) 1-phosphate Figure 6.8 synthase phosphorylase Extracellular Intracellular P i P i 6-31 LIPIDS Triglycerides are stored in body s adipocytes constant turnover of lipid molecules every - 3 weeks released into blood, transported and either oxidized or redeposited in other fat cells Lipogenesis - synthesis of fat from other types of molecules amino s and sugars used to make fatty s and glycerol PGAL can be converted to glycerol 6-3 LIPIDS Lipolysis breaking down fat for fuel begins with the hydrolysis of a triglyceride to glycerol and fatty s stimulated by epinephrine, norepinephrine, glucocorticoids, thyroid hormone, and growth hormone glycerol easily converted to PGAL and enters the pathway of glycolysis generates only half as much as glucose beta oxidation in the mitochondrial matrix catabolizes the fatty components removes two carbon atoms at a time which bonds to coenzyme A forms acetyl-coa, the entry point for the citric cycle a fatty with 16 carbons can yield 19 molecules of LIPOGENESIS AND LIPOLYSIS PATHWAYS Stored triglycerides Glycerol Fatty s Beta oxidation Acetyl groups 6-phosphate PGAL Pyruvic Acetyl-Co A Ketone bodies β-hydroxybutyric Acetoacetic Acetone Citric cycle Glycerol Fatty s New triglycerides Key Lipogenesis Lipolysis richer source of energy than the glucose molecule KETOGENESIS Fatty s catabolized into acetyl groups (by beta-oxidation in mitochondrial matrix) may: enter citric cycle as acetyl-coa undergo ketogenesis metabolized by liver to produce ketone bodies acetoacetic -hydroxybutyric acetone rapid or incomplete oxidization of fats raises blood ketone levels (ketosis) and may lead to a ph imbalance (ketoosis) PROTEINS Amino s in the pool can be converted to others Free amino s also can be converted to glucose and fat or directly used as fuel Conversions involve three processes: deamination removal of an amino group (-NH ) amination addition of -NH transamination transfer of -NH from one molecule to another As fuel - first must be deaminated (removal of -NH ) what remains is keto and may be converted to pyruvic, acetyl-coa, or one of the s of the citric cycle during shortage of amino s, citric cycle intermediates can be aminated and converted to amino s in gluconeogenesis, keto s are used to synthesis glucose
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