What Starts it All Energy, Enzymes, and Metabolism

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1 What Starts it All Energy, Enzymes, and Metabolism What is Energy? The transformation of energy is a hallmark of life. Energy is the capacity to do work, or the capacity to change. Energy transformations are linked to chemical transformations in cells. All forms of energy can be placed in two categories: Potential energy is stored energy as chemical bonds, concentration gradient, charge imbalance, etc. Kinetic energy is the energy of movement. Metabolism Metabolism: sum total of all chemical reactions in an organism Anabolic reactions: complex molecules are made from simple molecules; energy input is required. Catabolic reactions: complex molecules are broken down to simpler ones and energy is released. Laws of Thermodynamics First Law of Thermodynamics: Energy is neither created nor destroyed. When energy is converted from one form to another, the total energy before and after the conversion is the same. Second Law of Thermodynamics: When energy is converted from one form to another, some of that energy becomes unavailable to do work. No energy transformation is 100 percent efficient. Energy Calculation In any system: total energy = usable energy + unusable energy Enthalpy (H) = Free Energy (G) + Entropy (S) or H = G + TS (T = absolute temperature) G = H TS Change in energy can be measured in calories or joules. Change in free energy ( G) in a reaction is the difference in free energy of the products and the reactants. Gibbs Free Energy G = H T S

2 If G is negative, free energy is released. If G is positive, free energy is consumed. If free energy is not available, the reaction does not occur. Magnitude of G depends on: H total energy added ( H > 0) or released ( H < 0). S change in entropy. Large changes in entropy make G more negative. If a chemical reaction increases entropy, the products will be more disordered. Example: hydrolysis of a protein into its component amino acids S is positive. Second Law of Thermodynamics: Disorder tends to increase because of energy transformations. Living organisms must have a constant supply of energy to maintain order. Exergonic vs. Endergonic Exergonic reactions release free energy ( G) catabolism Endergonic reactions consume free energy (+ G) anabolism In principle, chemical reactions can run in both directions. Chemical equilibrium G = 0 Forward and reverse reactions are balanced. Every reaction has a specific equilibrium point. G is related to the point of equilibrium: the further towards completion the point of equilibrium is, the more free energy is released. G values near zero characteristic of readily reversible reactions. ATP ATP (adenosine triphosphate) captures and transfers free energy. ATP releases a large amount of energy when hydrolyzed. ATP can phosphorylate, or donate phosphate groups to other molecules. What Is the Role of ATP in Biochemical Energetics? ATP is a nucleotide. Hydrolysis of ATP yields free energy. G = 7.3 kcal/mole

3 Bioluminescence an endergonic reaction What Are Enzymes? Catalysts speed up the rate of a reaction. The catalyst is not altered by the reactions. Most biological catalysts are enzymes (proteins) that act as a framework in which reactions can take place. Some reactions are slow because of an energy barrier = the amount of energy required to start the reaction activation energy (Ea) Activation energy changes the reactants into unstable forms with higher free energy transition state species. Activation energy can come from heating the system the reactants have more kinetic energy. Enzymes lower the energy barrier by bringing the reactants together. Biological catalysts (enzymes and ribozymes) are highly specific. Reactants are called substrates. Substrate molecules bind to the active site of the enzyme. Three-dimensional shape of the enzyme determines the specificity. The enzyme-substrate complex is held together by hydrogen bonds, electrical attraction, or covalent bonds. E + S ES E + P The enzyme may change when bound to the substrate, but returns to its original form. Acid-base catalysis: enzyme side chains transfer H+ to or from the substrate a covalent bond breaks Covalent catalysis: a functional group in a side chain bonds covalently with the substrate Metal ion catalysis: metals on side chains loose or gain electrons Shape of enzyme active site allows a specific substrate to fit the lock and key. Many enzymes change shape when they bind to the substrate induced fit. Some enzymes require partners : Prosthetic groups: non-amino acid groups bound to enzymes

4 Cofactors: inorganic ions Coenzymes: not bound permanently to enzymes The rate of a catalyzed reaction depends on substrate concentration. Concentration of an enzyme is usually much lower than concentration of a substrate. At saturation, all enzyme is bound to substrate maximum rate. Rate can be used to calculate enzyme efficiency: molecules of substrate converted to product per unit time also called turnover. Ranges from 1 to 40 million molecules per second! How Are Enzyme Activities Regulated? Thousands of chemical reactions are occurring in cells simultaneously. The reactions are organized in metabolic pathways. Each reaction is catalyzed by a specific enzyme. The pathways are interconnected. Regulation of enzymes and thus the rates of reactions helps maintain internal homeostasis. Metabolic pathways can be modeled using mathematical algorithms. This new field is called systems biology. Inhibitors regulate enzymes: a molecule that binds to the enzyme and slows reaction rates. Naturally occurring inhibitors regulate metabolism. Irreversible inhibition: inhibitor covalently bonds to side chains in the active site permanently inactivates the enzyme. Example: DIPF or nerve gas Reversible inhibition: inhibitor bonds noncovalently to the active site, prevents substrate from binding competitive inhibitors. When concentration of competitive inhibitor is reduced, it detaches from the active site. Noncompetitive inhibitors: bind to the enzyme at a different site (not the active site). The enzyme changes shape and alters the active site. Allostery (allo, different ; stery, shape

5 Some enzymes exist in more than one shape: Active form can bind substrate Inactive form cannot bind substrate but can bind an inhibition 6.5 How Are Enzyme Activities Regulated? Most allosteric enzymes are proteins with quaternary structure. Active site is on one subunit, the catalytic subunit Inhibitors and activators bind to the regulatory subunits Metabolic pathways: The first reaction is the commitment step other reactions then happen in sequence. The final product may allosterically inhibit the enzyme needed for the commitment step, which shuts down the pathway feedback inhibition or end-product inhibition. Every enzyme has an optimal ph. ph influences the ionization of functional groups. Example: at low ph (high H+) COO may react with H+ to form COOH which is no longer charged affects folding and thus enzyme function. Every enzyme has an optimal temperature. At high temperatures, noncovalent bonds begin to break. Enzyme can lose its tertiary structure and become denatured. Isozymes: enzymes that catalyze the same reaction but have different properties, such as optimal temperature. Organisms can use isozymes to adjust to temperature changes. Enzymes in humans have higher optimal temperature than enzymes in most bacteria a fever can denature the bacterial enzymes.