Directions and Rates of Biochemical Processes Chapter 5

Ludwig Boltzmann, an Austrian physiscist, working around 1906 favored the idea that the behavior of atoms accounts for all chemical transformations. At this time few thought that atoms were real. The idea was first theorized by Democritus in the 5 th century B. C. then was abandoned for 2000 years.

About the time Boltzmann was working Albert Einstein proposed that Brownian movement was probably due to atoms. They did not communicate. Boltzmann despaired that his life’s work had been a waste and hung himself. Today his ideas are called the First and Second Laws of Thermodynamics.

Thermodynamics is the study of the relationships between different forms of energy. His work also involved kinetics, the study of rates of reactions. In general 2 questions must be asked: 1. Which way will the reaction go? 2. How fast will it go?

Ex. of rate Why does gasoline or oil burn quickly but take millions of years to form? Ex. of direction, Why does water fall down? Biological processes also have a definite direction. Predicting it lies in understanding that energy gets converted from one form to another. Thermodynamics governs all energy changes.

Work requires energy because it is movement against a force. Energy for work can be stored in a battery (potential) and used when the movement (kinetic) is needed. Rearranging atoms in a chemical reaction is a form of work.

Making a molecule of ATP requires putting together 3 negatively charged phosphate groups (goes against electrical force) but stores energy as potential energy. ATP can later be used to do work. ATP ADP; muscles move.

Going back to predicting the direction of a reaction, much was learned by watching steam engines. As coal burned the engine caused movement. However, energy is not destroyed or created, it just changes form. The First Law of Thermodynamics states the total amount of energy in any process stays the same.

The Second Law of Thermodynamics states that in any process the amount of energy available to do work decreases. According to the second Law of thermodynamics muscle contraction can only convert part of the potential energy in ATP into muscular contraction (kinetic). The rest becomes heat because of the random movement of molecules.

Energy is measured in calories, the amount of energy needed to raise the temperature of one gram of water one degree Celsius. Food is measured in Calories (1000 x larger units than calories). Whenever energy changes form, more energy turns to work. Heat loss is a result of energy transformation. Reactions usually go in the direction of heat loss.

To predict the direction of a chemical reaction you need to know how much free energy there is minus the energy for doing work. (G) Every chemical reaction involves a change in free energy. When 2 reactants form new products the change in energy is equal to the free energy of the products minus the free energy of the reactants. (Δ G)

Δ G + G products minus G reactants. All processes that release energy are exergonic which give off heat. ATP ADP + P. Reactions that require input of energy are endergonic. ADP + P ATP is endergonic, required heat in calories.

In all exergonic processes, free energy decreases so Δ G is negative. If free energy increases, Δ G is positive. Endergonic reactions are not spontaneous. ATP + H 2 O ADP + P (reactants) (products)

H replaces the O in the ATP’s 3 rd phosphate group. 2 bonds break, O-H and P-O. The new P-O bond is more stable. Free energy decreases when unstable bonds break and stable bonds form.

The free energy of the products ( ADP + P) hass less than free energy of the reactants. Biochemists call the unstable bonds of ATP high – energy bonds (~). ATP can be written out as: adenine + ribose + P ~ P.

The free energy for the breakdown of ATP ADP is -7. 3 kcal/mole. A mole is 6. 02 x 1023. The breakdown of ATP is the most common source of energy for biochemical processes. When an exergonic reaction drives an endergonic reaction the 2 processes are coupled. A coupled process must be exergonic overall.

Energy from splitting ATP drives reactions in small steps. Reactions are coupled by enzymes (proteins) that speed up biochemical processes. Enzymes do not change the free energy of the reaction like sliding down a hill of ice rather than dirt. , the reaction happens faster. In muscle contraction, an enzyme couples the breakdown of ATP to the contraction of muscle filaments.

The Second Law of Thermodynamics, that energy for work always decreases implies the amount of disorder in the universe always increases. A measure of disorder is entropy. Entropy is high when things are disordered and low when ordered. Entropy tends to increase as is can be used to do work.

A process that converts an orderly arrangement to a less orderly arrangement can perform work. Burning wood converts the well – ordered molecules of cellulose to disordered molecules of CO 2 and H 2 O. Energy from this reaction can cook or heat. A process to convert a disorderly arrangement to an orderly one consumes energy. For a tree to grow, light energy and O 2 are used to build cellulose.

Cells use energy and maintain concentration of molecules inside the cell that are different than those outside of the cell. Cells must perform work to keep their internal environment constant. When no energy is available to perform work the difference between the inside and outside disappear - lethal for the cell.

Therefore free energy depends on the concentration of molecules. The greater the difference in a concentration gradient the more work can be done. Reaction A B Reactant Product As B accumulates there is less free energy available for the reaction.

When the free energy of B = the free energy of A, Δ G = 0. The reaction is not downhill, equilibrium is reached. Thermosynamics can predict where equilibrium lies. When a substance absorbs heat and temperature increases the molecules bounce more rapidly – kinetic energy. The minimum energy needed to start a reaction is called activation energy.

Catalysts lower activation energy. Enzymes are biological catalysts. Most enzymes are proteins. Enzymes allow organisms to lower activation energy and shorten the time to attain equilibrium which is essential to life. Kinetic theory helps us understand why some thermodynamically favored reactions take place and others do not.

The presence of an active enzyme allows a cell to use ATP in specific ways; contraction of a muscle, pumping of ions in or out of a cell, or making other molecules. Enzymes bind to the reacting molecule (substrate) making a chemical reaction go 1 million x faster than it normally would.

Ex. At 0 degrees C. one molecule of catalase can break down 5 million molecules of H 2 O 2/minute. Enzymes are specific. Each one catalyzes only one reaction. This is because of their shape (remember proteins have a secondary, tertiary, and sometimes quaternary shape) and interactions with the substrate.

Most enzymes are large, globular proteins with irregular shapes. Each enzyme has an “active site” where it will bind with the substrate molecularly (like jigsaw puzzle pieces). Binding lowers activation energy for a particular reaction. Enzymes bond temporarily to substrates by weak covalent bonds, even H bonds and ionic bonds.

Binding of enzyme and substrate is reversible. Some enzymes can alter and release more than 600, 000 x per second. Interactions between enzymes and substrates occur one molecule at a time. The rate of reactions depends on temperature as well as concentration of reactants, and how much enzyme is present.

Forming noncovalent bonds between enzymes and substrates leaves the enzyme unchanged. The enzyme briefly changes the shape of the substrate. Enzymes bring substrates together in position to unite. The enzyme can alter covalent bonds on substrates and they break more easily.

The changed substrate is a transition state intermediate between starting molecules and the final product. This lasts a billionth of a second. Once the activation energy is changed the enzyme leaves.

In some cases the enzyme may lend an atom or ion. Enzymes work best at certain temperatures, p. H values, and salt concentrations. In mammals most work best at body temperature.

Some chemical reactions work better at higher temperatures because mlecules possess more kinetic energy. Increasing the temperature of an enzyme only works to a point because enzymes are proteins, bonds loosen and break. When a protein loses its shape and activity it is said to be denatured.

In organisms temperatures higher than 40 degrees C. are usually unfavorable. A few can survive like archaebacteria that live in hot springs. Enzymes also have only a small range of p. H where they work. p. H can alter an enzyme by adding or removing atoms changing its shape and the way it binds to a substrate.

Most cell enzymes require an environment between 6 and 8 but pepsin in the stomach works best at 2. The more food you put in your stomach the higher the p. H gets and at 5 the enzyme stops working. Some enzymes act as acids and bases. They can donate or accept H ions to a reaction. By regulating p. H cells control what enzymes can do.

Highly acid environments are usually unfavorable. This makes vinegar a good preservative for pickled foods. Northern bogs (cranberry and blueberry) are also strange places where vegetation like peat moss floating on water will not decay after it dies. Layers build up and finally you can jump and bounce on mats of peat.

Enzymatic reactions must occur in small steps with each step of a process being controlled by a different enzyme. There are 10 different reactions and 10 different enzymes necessary for the initial part of the breakdown of glucose. Most organisms including bacteria use these same 10 steps. The complexity is due to 4 reasons.

1. Chemical transformations are complex and require many steps. 2. Many reactions are endergonic to preceding exergonic reactions. ATP ADP. (espeially synthesis of large molecules from small ones, anabolism). 3. Many ergonic reactions would produce too much heat. (such as breaking down food, catabolism).

4. In some reactions intermediate products are starting molecules for synthesis of building blocks. Ex. Intermediate steps in breakdown of sugars to CO 2 and H 2 O are precursors for amino acids (building blocks of protein).

The variety of molecules in cells gives rise to many reactions. Enzymes regulate the rate of these reactions in response to environmental change. Organisms have ways to detect when they have built enough of a substance to avoid wasting energy. Ex. Cells make the amino acid isoleucine from threonine. This requires 5 enzymatic reactions which is energetically expensive.

When enough isoleucine has accumulated it shuts down this pathway by a negative feedback loop. Other molecules besides end products can inhibit the action of an enzyme. Enzymes that normally recognize the shape of an enzyme can be fooled into binding to molecules that are similar in size and shape.

Molecules similar to the substratecan block an enzymes active site and prevent the enzyme from working. This is inhibition by physical shape. In CO poisoning , CO competes for a site on the hemoglobin molecule. .

Unlike CO most steric inhibitors are reversible. Steric inhibitors can also be overcome if the concentration of substrate is high. The enzyme will bind to the substrate enough to block the inhibitor

Substrates and inhibitors compete for the same enzyme so the more concentrated substrate is the more effective the binding. The action of steric inhibitors is called competitive inhibition.

Some inhibitors are noncompetitive. Ex. Lead blocks specific groups out of the active site, which changes the shape and chemistry of the enzyme.

Inhibitors that bind to enzymes at other than the active sites are allosteric inhibitors. Noncompetitive inhibitors may bind to an an enzyme temporarily, others irreversibly. Penecillin irreversibly binds to enzymes necessary for bacteria to make cell walls. Most enzymes have evolved so that their active shape is their most stable shape.