Metabolism Chapter 8

I. Thermodynamics

Metabolism All the chemical reactions in an organism

Catabolic pathways Break down complex molecules into simpler molecules Releases energy Examples? Digestive enzymes break down food to release energy

Anabolic pathway Build complex molecules from simple molecules Consume energy Example: Body links amino acids to form muscle in response to exercise

Energy The ability to do work

Kinetic energy Energy of movement

Potential energy Stored energy as a result of position or structure Chemical energy – form of potential energy stored in molecules. On the platform, a diver has more potential energy. Diving converts potential energy to kinetic energy. Climbing up converts kinetic energy of muscle movement to potential energy. In the water, a diver has less potential energy. Figure 8.2

An example of energy conversion Figure 8.3  First law of thermodynamics: Energy can be transferred or transformed but Neither created nor destroyed. For example, the chemical (potential) energy in food will be converted to the kinetic energy of the cheetah’s movement in (b). (a) Chemical energy

Thermodynamics Study of energy transformation in matter First law: energy cannot be created or destroyed, only transferred or transformed 2nd law: Energy that is transferred or transformed increases entropy or the amount of disorder or randomness in the universe

The Second Law of Thermodynamics Figure 8.3  Second law of thermodynamics: Every energy transfer or transformation increases the disorder (entropy) of the universe. For example, disorder is added to the cheetah’s surroundings in the form of heat and the small molecules that are the by-products of metabolism. (b) Heat co2 H2O +

II. Free energy

III. ATP - Adenine Phosphate groups Ribose Figure 8.8 NH2 HC CH C N O OH N C HC NH2 Adenine Ribose Phosphate groups - CH

Energy coupling Use of exergonic process to drive an endergonic one

ATP Primary source of energy for coupling Made up of adenine bound to ribose and three phosphate groups When ATP is hydrolyzed energy is released in an endergonic reation

Energy is released from ATP When the terminal phosphate bond is broken Figure 8.9 P Adenosine triphosphate (ATP) H2O + Energy Inorganic phosphate Adenosine diphosphate (ADP) P i ATP drives endergonic reactions By phosphorylation, transferring a phosphate to other molecules

ADP When ATP is hydrolyzed it become ADP How many phophates does ADP have? ATP synthesis from ADP + P i requires energy ATP ADP + P i Energy for cellular work (endergonic, energy- consuming processes) Energy from catabolism (exergonic, energy yielding processes) ATP hydrolysis to ADP + P i yields energy Figure 8.12

IV. Enzymes

Catalyst Changes the rate of a chemical reaction without being altered in the process

Enzymes Macromolecules that are biological catalysts Considered proteins

Activation energy Amount of energy it takes to start a reaction, or the amount of energy it takes to break the bonds of reactant molecules Enzymes speed up reactions by LOWERING activation energy

Exergonic reaction – energy released Progress of the reaction Products Course of reaction without enzyme Reactants with enzyme EA EA with is lower ∆G is unaffected by enzyme Free energy Figure 8.15

Endergonic reaction – energy required

Parts of enzymes Substrate: enzyme reactants Active sites: site where substrate binds Enzyme substrate complex: formed when the substrate and enzyme bind After substrate binds it is converted into products which are released from the enzyme

Figure 8.16 Substate Active site Enzyme (a)

Induced fit of a substrate Brings chemical groups of the active site into positions that enhance their ability to catalyze the chemical reaction Figure 8.16 (b) Enzyme- substrate complex

The catalytic cycle of an enzyme Substrates Products Enzyme Enzyme-substrate complex 1 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. 3 Active site (and R groups of its amino acids) can lower EA and speed up a reaction by • acting as a template for substrate orientation, • stressing the substrates and stabilizing the transition state, • providing a favorable microenvironment, • participating directly in the catalytic reaction. 4 Substrates are Converted into Products. 5 Products are Released. 6 Active site Is available for two new substrate Mole. Figure 8.17

Enzyme activity Activity of an enzyme can be affected by several factors: Changes in Temperature pH Changes in temperature and pH can change the shape of the enzyme, making it less effective

Cofactors Non-protein helpers Include metals like zinc, iron and copper Function to allow catalysis to occur

Coenzymes Organic cofactors such as vitamins

Competitive inhibitors Reversible inhibitors that compete with the substrate for the active site Very similar to normal substrate Figure 8.19 (b) Competitive inhibition A competitive inhibitor mimics the substrate, competing for the active site. Competitive inhibitor A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme (a) Normal binding

Noncompetitive inhibitors Prevent enzyme activity by binding to anotehr part of the enzyme Cause change in shape Figure 8.19 A noncompetitive inhibitor binds to the enzyme away from the active site, altering the conformation of the enzyme so that its active site no longer functions. Noncompetitive inhibitor (c) Noncompetitive inhibition

V. Enzyme activity regulation

Allosteric site Specific binding site other than the active site where regulators bind and change the shape of the enzyme. Can either stimulate OR inhibit the activity

Figure 8.20 Allosteric activater stabilizes active from Stabilized inactive form Allosteric activater stabilizes active from Allosteric enyzme with four subunits Active site (one of four) Regulatory site (one of four) Active form Activator Stabilized active form Allosteric activater stabilizes active form Inhibitor Inactive form Non- functional active site (a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again. Oscillation Figure 8.20

Feedback inhibition The end product of an enzymatic pathway can switch off the pathway by binding to the allosteric site (the result!) Increases efficiency of pathway by turning off when the end product accumulates in the cell.

Feedback inhibition Figure 8.21 Initial substrate (threonine) Active site available Isoleucine used up by cell Feedback inhibition Isoleucine binds to allosteric site Active site of enzyme 1 no longer binds threonine; pathway is switched off Initial substrate (threonine) Threonine in active site Enzyme 1 (threonine deaminase) Intermediate A Intermediate B Intermediate C Intermediate D Enzyme 2 Enzyme 3 Enzyme 4 Enzyme 5 End product (isoleucine) Figure 8.21