Chapters 2.5,3.3,3.4: Energy&Enzymes

Enzymes Lower the Energy Barrier

•Enzymes lower the activation energy by enabling reactants to come together and react more easily. •Ex: A molecule of sucrose in solution may hydrolyze in ~15 days; with sucrase present, the same reaction occurs in 1 second!

Biochemical Changes Involve Energy

-Chemical reactions occur when atoms have enough energy to combine or change bonding partners. Example of a "Chemical Equation": sucrose + H2O glucose + fructose (C12H22O11) (C6H12O6) (C6H12O6) reactants products Chemical reactions involve changes in energy. -Energy = the capacity to do work (the capacity for change) In biochemical reactions, energy changes are usually associated with changes in the chemical composition and properties of molecules. All forms of energy can be considered as either: •Potential - the energy of state or position, or stored energy •Kinetic - the energy of movement; the type of energy that does work; that makes things change. Energy can be converted from one form to another. -Metabolism—sum total of all chemical reactions occurring in a biological system at a given time Metabolic reactions involve energy changes. Energy is either stored in, or released from, chemical bonds. A chemical reaction will occur spontaneously if the total energy consumed by breaking bonds in the reactants is less than the total energy released by forming bonds in the products.

Activation Energy Initiates Reactions

Activation energy can come from heat—the molecules have more kinetic energy. •This would not work in living systems because all reactions would be accelerated, including destructive ones.

Some Enzymes Change Shape When Substrate Binds to Them

Enzyme 3-D structures are so specific that they bind only one or a few related substrates. •Many enzymes change shape when the substrate binds; "induced fit."

Regulation of Metabolism Occurs by Regulation of Enzymes

Enzyme-catalyzed reactions operate in metabolic pathways. Product of one reaction is a substrate for the next reaction & each step catalyzed by a specific enzyme •Cell have hundreds of enzymes that participate in interconnecting metabolic pathways, forming a metabolic system. Cells can regulate metabolism by controlling the amount of an enzyme. •Cells often have the ability to turn synthesis of enzymes off or on. •Activity of enzymes can also be regulated, which is often faster. •Chemical inhibitors can bind to enzymes and slow reaction rates. -Natural inhibitors regulate metabolism. -Artificial inhibitors are used to treat diseases, kill pests, and study enzyme function

Biochemical System

Enzymes are a major element controlling these pathways. The complex interactions of metabolic pathways can be studied using the tools of systems biology (computer/mathematical algorithms)

Enzyme Action

Enzymes are highly specific - each one catalyzes only one chemical reaction. •Reactants are substrates: they bind to specific sites on the enzyme—the active sites. •Specificity results from the exact 3-D shape and chemical properties of the active site.

The enzyme-substrate complex (ES) is held together by H-bonding, electrical attraction, or temporary covalent bonding. The enzyme is not changed at the end of the reaction.

Enzymes use one or more mechanisms to catalyze a reaction: •Inducing strain—bonds in the substrate are stretched, putting it in an unstable transition state. Substrate orientation—substrates are brought together so that bonds can form. •Adding chemical groups—R groups may be directly involved in the reaction.

^continued

Irreversible inhibition: -Inhibitor covalently binds to a side chain in the active site & the enzyme is permanently inactivated. -Some insecticides act in this way. Reversible inhibition: •A competitive inhibitor •A noncompetitive inhibitor (aka. Allosteric regulation) Allosteric regulation—non-substrate molecule binds a site other than the active site (the allosteric site) -The enzyme changes shape, which alters the chemical attraction (affinity) of the active site for the substrate. -Allosteric regulation can activate or inactivate enzymes. Phosphorylation by protein kinases is an important regulatory mechanism. •Phosphorylation can change a hydrophobic region to hydrophilic. The enzyme twists and exposes the active site. •Protein phosphatases reverse the process by removing phosphate groups. pH affects protein structure & enzyme activity: -Acidic side chains generate H+ and become anions. -Basic side chains attract H+ and become cations Example: glutamic acid—COOH glutamic acid—COO- + H+ •The law of mass action: the higher the H+ concentration, the more the reaction is driven to the left, to the less hydrophilic form. •This can affect enzyme shape and function Protein tertiary structure (and thus function) is very sensitive to the concentration of H+ (pH) in the environment. * All enzymes have an optimal pH for activity. Temperature affects protein structure & enzyme activity: -Warming increases rates of chemical reactions, but if temperature is too high, noncovalent bonds can break, inactivating enzymes. *All enzymes have an optimal temperature for activity Isozymes catalyze the same reaction but have different composition and physical properties. •Isozymes may have different optimal temperatures or pH, allowing an organism to adapt to changes in its environment. •Ex: Rainbow trout - has several isozymes of the enzyme acetylcholinesterase active at different temperatures

Some Proteins Act as Enzymes to Speed up Biochemical Reactions

Living systems depend on reactions that occur spontaneously, but at very slow rates. •Catalysts are substances that speed up the reactions without being permanently altered. •No catalyst makes a reaction occur that cannot otherwise occur. •Most biological catalysts are proteins (enzymes); a few are RNA molecules (ribozymes). An exergonic reaction releases free energy (G), the amount of energy in a system that is available to do work. •Without a catalyst, the reaction will be very slow because there is an energy barrier between reactants and products. •An input of energy initiates the reaction (activation energy or Ea), which puts reactants into a transition state.

Catalyzed Reactions Reach a Maximum Rate

Rates of catalyzed reactions: -There is usually less enzyme than substrate present, so reaction rate levels off when all enzyme molecules are bound to substrate molecules. •The enzyme is said to be saturated.

The Laws of Thermodynamics

The laws of thermodynamics ("energy" "changes") apply to all matter and energy transformations in the universe. •First law: Energy is neither created nor destroyed. •Second law: Useful energy tends to decrease. When energy is converted from one form to another, some of that energy becomes unavailable for doing work. No physical process or chemical reaction is 100% efficient - some of the released energy is lost in a form associated with disorder. •This energy is so dispersed that it is unusable. •Entropy = a measure of the disorder in a system. (As a result of energy transformations, disorder tends to increase.) -If a chemical reaction increases entropy, its products are more disordered or random than its reactants. -If there are fewer products than reactants, the disorder is reduced; this requires energy to achieve.

^continued

Two basic types of metabolism: •Anabolic reactions link simple molecules to form complex ones. ●require energy inputs (endergonic or endothermic; energy is captured in the chemical bonds that form. •Catabolic reactions: energy is released (exergonic or exothermic) ●Complex molecules broken down into simpler ones. ●Energy stored in the chemical bonds is released. Catabolic and anabolic reactions are often linked. The energy released in catabolic reactions is often used to drive anabolic reactions—to do biological work.