A. Metabolism, Energy, and Life
1. The chemistry of life is organized into metabolic pathways.
a. The totality of an organism�s chemical reactions is called metabolism.
b. Metabolic pathways alter molecules in a series of steps.
1. Catabolic pathways release energy by breaking down complex molecules to simpler compounds (cellular respiration).
2. Anabolic pathways consume energy to build complicated molecules from simpler compounds (photosynthesis).
2. Organisms transform energy.
a. Energy is the capacity to do work.
b. Energy can be converted from one form to another.
c. Catabolic pathways unleash energy stored in sugar and other complex molecules.
d. This energy is available for cellular work.
e. The chemical energy stored in these organic molecules was derived primarily from light energy by plants during photosynthesis.
f. A central property of living organisms is the ability to transform energy.
3. ATP powers cellular work.
a. A cell does three main kinds of work.
1. Mechanical work, beating of cilia, contraction of muscle cells, and movement of chromosomes.
2. Transport work, pumping substances across membranes against the direction of spontaneous movement.
3. Chemical work, driving reactions such as the synthesis of polymers from monomers.
b. In most cases, the immediate source of energy that powers cellular work is ATP.
c. ATP (adenosine triphosphate) is a type of nucleotide consisting of the nitrogenous base adenine, the sugar ribose, and a chain of three phosphate groups. (Fig. 6.8)
d. The bonds between phosphate groups can be broken by hydrolysis.
1. Hydrolysis of the end phosphate group forms adenosine diphosphate [ATP > ADP + Pi] and releases energy.
e. The phosphate bonds of ATP are unstable and their hydrolysis yields energy because the products are more stable.
1. The phosphate bonds are weak because each of the three phosphate groups has a negative charge.
2. Their repulsion contributes to the instability of this region of the ATP molecule.
f. In the cell the energy from the hydrolysis of ATP is coupled directly to processes by transferring the phosphate group to another molecule. (Fig. 6.9)
1. This molecule is now phosphorylated.
2. This molecule is now more reactive.
g. ATP is a renewable resource that is continually regenerated by adding a phosphate group to ADP. (Fig. 6.10)
1. In a working muscle cell the entire pool of ATP is recycled once each minute, over 10 million ATP are consumed and regenerated per second per cell.
B. Enzymes
1. Enzymes speed up metabolic reactions by lowering energy barriers.
a. A catalyst is a chemical agent that changes the rate of a reaction without being consumed by the reaction.
1. An enzyme is a catalytic protein.
b. Chemical reactions between molecules involve both bond breaking and bond forming. (Fig. 6.11)
1. To hydrolyze sucrose, the bond between glucose and fructose must be broken and then new bonds formed with a hydrogen ion and hydroxyl group from water.
2. Activation energy is needed to break the bonds. (Fig. 6.12)
a. This energy makes the reactants unstable, increases the speed of the reactant molecules, and creates more powerful collisions.
b. Activation energy is the amount of energy necessary to push the reactants over an energy barrier.
c. For some processes, the barrier is not high and the thermal energy provided by room temperature is sufficient to reach the transition state.
d. In most cases, EA is higher and a significant input of energy is required.
1. However, in the temperatures typical of the cell there is not enough energy for a vast majority of molecules to make it over the hump of activation energy.
2. Yet, a cell must be metabolically active.
3. Heat would speed reactions, but it would also denature proteins and kill cells.
e. Enzymes speed reactions by lowering EA-the transition state can then be reached even at moderate temperatures. (Fig. 6.13)
2. Enzymes are substrate specific.
a. A substrate is a reactant that binds to an enzyme.
b. When a substrate, or substrates, bind to an enzyme, the enzyme catalyzes the conversion of the substrate(s) to the product(s).
1. Sucrase is an enzyme that binds to sucrose and breaks the disaccharide into fructose and glucose.
c. The active site of an enzyme is typically a pocket or groove on the surface of the protein into which the substrate fits. (Fig. 6.14)
d. The specificity of an enzyme is due to the fit between the active site and that of the substrate.
e. As the substrate binds, the enzyme changes shape leading to a tighter induced fit, bringing chemical groups in position to catalyze the reaction.
3. The active site is an enzyme�s catalytic center.
a. In most cases substrates are held in the active site by weak interactions, such as hydrogen bonds and ionic bonds.
b. A single enzyme molecule can catalyze thousands or more reactions a second.
c. Enzymes are unaffected by the reaction and are reusable. (Fig. 6.15)
d. Enzymes use a variety of mechanisms to lower activation energy and speed a reaction.
1. The active site orients substrates in the correct orientation for the reaction.
2. As the active site binds the substrate, it may put stress on bonds that must be broken, making it easier to reach the transition state.
3. Variable groups at the active site may create a conducive microenvironment for a specific reaction.
4. Enzymes may even bind covalently to substrates in an intermediate step before returning to normal.
e. The rate that a specific number of enzymes converts substrates to products depends in part on substrate concentrations.
1. An increase in substrate speeds binding to available active sites.
2. However, there is a limit to how fast a reaction can occur.
3. At some substrate concentrations, the active sites on all enzymes are engaged, called enzyme saturation.
f. The only way to increase productivity at this point is to add more enzyme molecules. (CD Activity 6D)
4. A cell�s physical and chemical environment affects enzyme activity.
a. The three-dimensional structures of enzymes (almost all proteins) depend on environmental conditions.
1. Changes in shape (conformation) influence the reaction rate.
2. Some conditions lead to the most active conformation and lead to optimal rate of reaction.
b. Temperature has a major impact on reaction rate. (Fig. 6.16)
1. As temperature increases, collisions between substrates and active sites occur more frequently as molecules move faster.
2. However, at some point thermal agitation begins to disrupt the weak bonds that stabilize the protein�s active conformation and the protein denatures.
3. Each enzyme has an optimal temperature.
c. Because pH also influences shape and therefore reaction rate, each enzyme has an optimal pH.
1. This falls between pH 6 - 8 for most enzymes.
2. However, digestive enzymes in the stomach are designed to work best at pH 2 while those in the intestine are optimal at pH 8, both matching their working environments.
d. Many enzymes require nonprotein helpers, cofactors, for catalytic activity.
1. They bind permanently or reversibly to the enzyme.
2. Some inorganic cofactors include zinc, iron, and copper.
3. Organic cofactors, coenzymes, include vitamins or molecules derived from vitamins.
e. Binding by some molecules, inhibitors, prevent enzymes from catalyzing reactions. (Fig. 6.17)
1. If binding involves covalent bonds, then inhibition is often irreversible.
2. If binding is weak, inhibition may be reversible.
3. If the inhibitor binds to the same site as the substrate, then it blocks substrate binding via competitive inhibition.
4. If the inhibitor binds somewhere other than the active site, it blocks substrate binding via noncompetitive inhibition.
a. Binding by the noncompetitive inhibitor causes the enzyme to change shape, rendering the active site unreceptive (at worst) or less effective at catalyzing the reaction.
C. The Control of Metabolism
1. Metabolic control often depends on allosteric regulation.
a. In many cases, the molecules that naturally regulate enzyme activity bind reversibly to an allosteric site, a specific receptor on the enzyme that is not the active site. (Fig. 6.18)
1. Activators stabilize the enzyme in its active form.
2. Inhibitors stabilize the enzyme in its inactive form
b. One of the common methods of metabolic control is feedback inhibition in which a metabolic pathway is turned off by its end product. (Fig. 6.19)
1. The end product acts as an inhibitor of an enzyme in the pathway.
2. When the product is abundant the pathway is turned off, when rare the pathway is active.
2. Multienzyme complexes-localization of enzymes within a cell helps order metabolism
a. Structures within the cell bring order to metabolic pathways.
b. A team of enzymes for several steps of a metabolic pathway may be assembled together as a multienzyme complex.
c. The product from the first can then pass quickly to the next enzyme until the final product is released.
d. Some enzymes and enzyme complexes have fixed locations within the cells as structural components of particular membranes.
e. Others are confined within membrane-enclosed eukaryotic organelles. (Fig. 6.19)
f. Both methods concentrate enzymes for efficiency.