Chemical Reactions in Cells Energetics, Enzymes and Metabolic Reactions

Energy Energy is the capacity for work or change. Kinetic Energy = energy of movement Potential Energy = stored energy 1st Law of Thermodynamics Energy can be transferred and transformed from one form to another but it cannot be created or destroyed.

Energy 2nd Law of Thermodynamics Energy transfer or transformation increases the entropy of the universe Increase in entropy = randomness Energy conversions result in a loss of useful energy usable

Free Energy = Energy Useful for Change Spontaneity of a reaction depends on free energy change G G reaction = Gproducts – Greactants If is negative, free energy is released and the reaction is spontaneous G If is positive, free energy is consumed G

Free Energy = Energy Useful for Change Free Energy change depends on changes in total energy (enthalpy) entropy (unusable energy, disorder) H S In living systems, entropy changes have substantial influence when is positive, and the term is large, a negative value predicts a spontaneous reaction S T G G H S T = –

Chemical Reactions Involve the breaking and formation of chemical bonds Reactants are converted to products. Two types of reactions based on energy use: Exergonic– free energy released Endergonic – free energy consumed

Burning glucose (sugar): an exergonic reaction Exergonic Reactions Burning glucose (sugar): an exergonic reaction Reactants changed to transition-state species Energy content of molecules high low Activation energy needed to ignite glucose Glucose + O2 G Energy released by burning glucose C O2 + H2O Progress of reaction

Energy content of molecules Endergonic Reactions Photosynthesis: an endergonic reaction Energy content of molecules high low Glucose Activation energy from light captured by photosynthesis Net energy captured by synthesizing glucose G CO2 + H2O Progress of reaction

Applying Your Knowledge Endergonic Reaction Exergonic Reaction A. Which type of reaction would be spontaneous? B. For which type of reaction will the products have a higher energy than the reactants? C. Which type of reaction releases energy? D. Which type of reaction would have a positive value for G?

ATP Provides Energy for Cellular Reactions + H2O + Pi + free energy

Short-Term Energy Storage Chemical Energy is stored in the bonds of ATP ATP = adenosine triphosphate ADP = adenosine diphosphate to store energy ADP + Phosphate + Energy ATP to release energy ATP  ADP + Phosphate + Energy

Coupled Reactions Pairing of an Exergonic reaction, often involving ATP, with an Endergonic reaction Note that overall free energy change is negative

Metabolic Reactions Anabolic Catabolic link simple molecules to produce complex molecules (eg. dehydration synthesis of starch) require energy Catabolic break down complex molecules to release simple ones (eg. hydrolysis of starch sugars) release energy stored in chemical bonds

Metabolic Pathways F G B A C E D Pathway 1 Pathway 2 Initial Reactants Intermediates Final Products D B E C A Enzyme 1 Enzyme 2 Enzyme 3 Enzyme 4 Pathway 1 F G Pathway 2 Enzyme 5 Enzyme 6

Enzymes Assist in Biological Reactions Enzymes are biological catalysts. biological: composed of protein or, rarely, RNA catalyst: speeds up a reaction without being changed by the reaction

Properties of Enzymes Enzymes speed up biological reactions by lowering the activation energy for the reaction. Enzymes provide a surface where the catalysis takes place The reaction reaches equilibrium more rapidly – The value of and the ratio of reactants and products at equilibrium is the same as for an uncatalyzed reaction G

Activation Energy: Controls Rate of Reaction Amount of energy required for reaction to occur transition state Energy content of molecules high low Activation energy without catalyst G Activation energy with catalyst Progress of reaction

Properties of Enzymes Enzymes are SPECIFIC for the reactants (substrates) in the reactions that they catalyze. Only substrates that fit the active site of the enzyme can bind and complete the reaction active site: region on enzyme where substrates bind

Enzyme-Substrate Interactions 1 Substrates enter active site Active Site 2 Shape change promotes reaction Enzyme Product released; enzyme ready again induced fit

Chemical Events at Active Sites Enzymes hold substrates in the proper orientation for the reaction to take place

Chemical Events at Active Sites Enzymes induce strain in the substrate to produce a transition state favorable to reaction Active site provides a microenvironment that favors the chemical reaction

Chemical Events at Active Sites Active site directly participates in the reaction covalent bonding can occur between enzyme and substrate R groups of the enzyme’s amino acids can temporarily add chemical groups to the substrates

Molecules that Assist Enzymes Cofactors: inorganic ions that bind to enzymes, eg. zinc Coenzymes: small organic factors that temporarily bind to enzymes, eg. biotin, NAD, ATP Prosthetic groups: non-protein factors that are permanently bound an enzyme, eg. heme

Factors Influencing Reaction Rate Rate no longer increases since the active sites of all enzymes are saturated with substrate Substrate Concentration Rate is more rapid Rate is proportional to substrate concentration

Factors Influencing Reaction Rate Competitive Inhibitors: Bind at the active site, compete for binding with substrate Irreversible: form covalent bond with amino acids in the active site DIPF

Factors Influencing Reaction Rate Competitive Inhibitors: Bind at the active site, compete for binding with substrate Reversible: molecule similar to substrate occupies active site but does not undergo reaction

Factors Influencing Reaction Rate Non-Competitive Inhibitors: Bind to a different site, cause a conformational change in the enzyme that alters the active site Reversible

Factors Influencing Reaction Rate Allosteric Regulation Conversion between active and inactive forms of an enzyme due to binding of regulatory molecules at an allosteric site Activators stabilize the active form Allosteric inhibitors stabilize the inactive form

Factors Influencing Reaction Rate Allosteric Regulation Cooperativity: a substrate causing induced fit in one enzyme subunit can cause a change to the active form in all the other subunits

Enzyme Regulation: Feedback Inhibition Commitment step CH2 C COOH CH3 NH3 H CH3 C COOH OH NH3 H A B C D Enz. 1 Enz. 2 Enz. 3 Enz. 4 Enz. 5 Feedback Inhibition Isoleucine allosterically inhibits enzyme 1 Threonine (substrate) Isoleucine (end product) Feedback Inhibition: The product of a pathway inhibits an initial step in the pathway to decrease its own production

Properties of Enzymes Three dimensional structure of an enzyme preserves its ACTIVE SITE Conditions that can affect three dimensional structure include: heat, pH (acid/base balance) and other chemicals (salt, charged ions)

Effects of Temperature and pH on Enzymatic Activity fewer collisions between enzyme and substrate enzyme unfolds (denatures) enzyme unfolds (denatures)

Applying Your Knowledge Active Site Activation Energy Allosteric Site Commitment step Induced fit Where can an inhibitor bind to stabilize the inactive form of an enzyme? Where do the substrates bind? Enzymes (raise or lower) the (1, 2, 3, 4 or 5) of a reaction. What is the model for a shape change caused by substrate binding to the enzyme?