Ch 8 An Introduction to Metabolism 8 1 An organism s metabolism transforms matter and energy subject to the laws of thermodynamics Metabolism The totality of an organism s chemical reactions Metabolic pathway Begins with a specific molecule which is transformed in a series of steps into a specific product each step of the pathway is catalyzed by a specific enzyme Anabolic synthesis vs Catabolic break down Energy The capacity to cause change o Kinetic Energy energy associated with the motion of objects o Thermal Energy kinetic energy associated with the motion of particles thermal energy transferred from one object to another is called heat o Potential Energy energy due to location or structure o Chemical Energy potential energy available for release in a chemical The study of the energy transformations that occur in a collection of matter is reaction called Thermodynamics o First law Energy can be transferred and transformed but it cannot be created nor destroyed o Second law Energy transfer or transformation increases the entropy of the universe Entropy measure of randomness Spontaneous energetically favorable 8 2 The Free Energy change of a reaction tells us whether or not the reaction occurs spontaneously Free energy change G The portion of a system s energy that can preform work when temperature and pressure are uniform throughout the system as in a living cell G 0 spontaneous G H T S H change in systems enthalpy S change in systems entropy o o o o T Temperature in K G G final state G initial state Exergonic reaction energy release spontaneous G Endergonic reaction energy required nonspontaneous G 8 3 ATP powers cellular work by coupling exergonic reactions to endergonic reactions Cell does 3 types of work o Chemical work the pushing of endergonic reactions that would not occur spontaneously such as the synthesis of polymers from monomers o Transport work the pumping of substances across membranes against the direction of spontaneous movement o Mechanical work such as the beating of cilia the contraction of muscle cells and the movement of chromosomes during cellular reproduction Energy coupling the use of exergonic reactions to fuel endergonic ones o ATP is responsible for mediating most energy coupling in cells and in most cases it acts as the immediate source of energy that powers cellular work ATP adenine triphosphate contains the sugar ribose with the nitrogenous base adenine and a chain of 3 phosphate groups triphosphate group When the bonds between the phosphate groups are broken by hydrolysis this creates ADP adenine di phosphate o ATP H2O ADP P G 7 3 kcal mol When phosphate group is broken off this releases energy in the cell high energy phosphate bonds How ATP drives chemical work energy coupling using ATP hydrolysis How ATP drives transport and mechanical work ATP hydrolysis causes changes in the shapes and binding affinities of proteins o Directly by phosphorylation o Indirectly by non covalent bonding of ATP and its hydrolytic products Regeneration of ATP o ATP Cycle Energy released by breakdown reactions catabolism in the cell is used to phosphorylate ADP regenerating ATP Chemical potential energy stored in ATP drives most cellular work 8 4 Enzymes speed up metabolic reactions by lowering energy barriers Enzyme macromolecule that acts like a catalyst The activation energy barrier The initial investment of energy for starting a reaction the energy required to contort the reactant molecules so the bond can break is known as the free energy of activation or activation energy Ea How enzymes speed up reactions o An enzyme catalyzes a reaction by lowering the activation energy enabling the reactant molecules to absorb enough energy to reach the transition state even at moderate temperatures Substrate specificity of enzymes o Substrate the reactant an enzyme acts on is referred to as that enzymes substrate o Enzyme substrate complex when the substrate enters the active site it forms weak bonds with the enzyme o Each reaction has a specific enzyme o Induced fit binding of enzyme and substrate becomes tighter after initial complex 1 Substrates enter active site enzyme changes shape such that its active site enfolds the substrates induced fit 2 Substrates are held in active site by weak interactions such as hydrogen bonds and ionic bonds 3 Substrates are converted to products 4 Products are released 5 Active site is available for two new substrate molecules Enzyme activity is affected by conditions such as pH and temperature as well as chemicals that specifically influence that enzyme Cofactors non protein helpers for catalytic activity Coenzyme organic cofactor Competitive inhibitors reduce the productivity of enzymes by blocking substrates from entering active sites o A competitive inhibitor mimics the substrate competing for the Noncompetitive inhibitors do not directly compete with the substrate to bind to the enzyme at the active site o Instead they impede enzymatic reactions by bonding to another part active site of the enzyme o A noncompetitive inhibitor binds to the enzyme away from the active site altering the shape of the enzyme so that even if the substrate can bind the active site functions less effectively if at all 8 5 Regulation of enzyme activity helps control metabolism Allosteric regulation any case in which a protein s function at one site is affected by the binding of a regulatory molecule to a separate site o May result in either inhibition or stimulation of an enzyme s activity Cooperativity a substrate molecule binding to one active site in a multisubunit enzyme triggers a shape change in all of the subunits thereby increasing catalytic activity at the other sites o This mechanism amplifies the response of enzymes to substrates One substrate molecule primes an enzyme to act on additional substrate molecules more readily Considered allosteric regulation because binding of the substrate to one active site affects catalysis in another site Feedback inhibition o When ATP allosterically inhibits an enzyme in an ATP generation pathway the result is feedback inhibition a common mode of metabolic control o A metabolic pathway is halted by the inhibitory binding of its end product to an enzyme that acts early in the pathway Localization of enzymes within the cell o Cells are compartmentalized o Some enzymes are grouped into complexes some are incorporated into membranes and some are contained inside organelles increasing the efficiency of metabolic
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