Macromolecules from Activated IntermediatesKinetic Energy Starts Reactions and ATP Is Used to Polymerize
A common misconception is that ATP can be used to determine the direction of a reaction. ATP is used to make activated intermediates that are macromolecular precursors.
A cell takes the energy from glucose and uses other simple nutrients to make a new cell. Highly complex proteins fold into functional enzymes capable of controlling biochemical pathways. All of this complexity and structure is achieved by random molecular collisions and energy relationships as simple as a ball rolling down a hill. Polymers are Made of MonomersBiology exploits the polymerization of small monomers into polymers. Hence, proteins, also called polypeptides, are made of hundreds of amino acids joined by peptide bonds. Polysaccharides are polymers of sugars. And nucleic acids, e.g. DNA and RNA, are made up of many individual nucleotides connected by phosphodiester bonds. In each case the large macromolecule is made by stringing together hundreds of linearly bonded monomers, over and over, instead of making one gigantic, complex molecule from hundreds of thousands of individual atoms. Macromolecules (Protein, Polysaccharide, Nucleic Acid) Are Higher Energy Molecules than their MonomersIn each case, a polymer macromolecule can be readily hydrolyzed by enzyme catalysts to produce lower energy monomers. The enzymes increase the rate of the reaction, but do not change the final outcome. Thus, in the stomach and intestines enzymes catalyze the digestion of proteins into amino acids and starch into glucose. This process shows that after the reaction is complete and the lowest energy products of reactions are obtained, the monomers are lower energy than the polymers. This means that energy is needed to make polymers from monomers. Biological macromolecules are not made directly from monomers. Proteins cannot be made from amino acids. There is too much water around (hydrolysis is favored) and the amino acid concentration is too low to drive the reaction in the direction of polymerization. The results of enzyme catalysis demonstrate the basic energy relationships, i.e. polymers are higher energy configurations than monomers. Activated Intermediates Using ATPThe biological answer is to make polymers from activated intermediates rather than directly from monomers. ATP can be used to convert monomers into high energy molecules, activated intermediates, that can combine with a release of energy to make polymers. RNA from Nucleotide Triphosphates, not from Nucleotide MonophosphatesRibonucleic acid, RNA, for example, is a polymer that can be hydrolyzed by ribonuclease to produce four ribonucleotide monophosphates, CMP, GMP, AMP and UMP. This process shows that the monomers are lower energy than the polymer RNA. The reaction cannot be reversed to force the monophosphates together to make RNA. This is like trying to convince a ball to roll back up a hill. Nucleotide Triphosphates Are Activated Intermediates in RNA SynthesisTransferase enzymes can be used, however, to transfer phosphates from ATP to convert the nucleotide monophosphates into the corresponding triphosphates, CTP, GTP, ATP and UTP. (Note that ATP is itself a ribonucleotide triphosphate activated intermediate for RNA synthesis and this is consistent with the view that RNA was the original nucleic acid in the evolution of cellular structure.) The high energy phosphates of the ATP are transferred to the monophosphates to make diphosphates and ultimately triphosphates. In cells the nucleotide triphosphates are then polymerized by RNA polymerase into RNA (using DNA as the template.) In each of the series of new reactions that make the activated intermediates (nucleotide triphosphates), the reactants have more energy in their arrangement of atoms than the products. Biological Polymers (Macromolecules) Made from their Activated Intemediates
Breaking Bonds Always Requires Energy Input, Even ATPNote that all bonds are by definition the result of molecules coming together into a lower energy arrangement and releasing energy. Breaking bonds, even in the case of ATP hydrolysis, requires an input of energy from the thermal, kinetic energy of colliding molecules. ATP can be used to make high energy arrangements of atoms that will tend to rearrange into other lower energy forms, e.g. activated intermediates that tend to polymerize. The formation of the activated intermediate requires the transfer of part of the ATP molecule, either a phosphate or the adenosine, to make the intermediate. Hydrolysis of ATP would non-productively release all of its chemical energy as kinetic energy and raise the temperature of the solution. ATP hydrolysis cannot be used to make anything but hot water.
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