Chapter 6 Ground Rules of Metabolism
I. The Old Man of the Woods
A. All living things have a need for energy.
B. Metabolism is the controlled capacity to acquire and use energy for the synthesis and breakdown of organic compounds.

II. Energy and Life
A. Energy is the capacity to make things happen, to cause change, to do work.
B. Two laws govern energy transformations:
1. First law of thermodynamics states that the total amount of energy in the universe is constant; it cannot be created nor destroyed; it can only change form.
a. Energy cannot be produced by a cell; it can only be borrowed from someplace else.
b. Energy can be of high quality, that is, highly concentrated and usable; or it can be of low quality, such as heat that is released into the universe.
2. Second law of thermodynamics states that the spontaneous direction of energy flow is from high- to low-quality forms.
a. Each conversion results in production of energy (usually heat) that is unavailable for work.
b. As systems lose energy they become more disorganized; the measure of this disorder is called entropy.
C. The world of life (plant and animal) maintains a high degree of organization only because it is being resupplied with energy from the sun.

III. The Nature of Metabolism
A. Energy Changes in Metabolic Reactions
1. Concepts concerning reactions:
a. Products (end of reaction) may have more or less energy than the reactants (beginning of reaction).
b. Most reactions are reversible.
c. Reversible reactions approach equilibrium.
2. Bond Energies
a. Bond energy is measured in kilocalories per mole.
b. Bond energies for covalent bonds are much higher (about 90) than those of ionic and hydrogen bonds (about 5).
3. Energy Losses and Gains
a. Exergonic (“energy out”) reactions release energy such that the products have less energy than the reactants had.
b. Endergonic (“energy in”) reactions require energy input resulting in products with more energy than the reactants had.
4. Reversible Reactions
a. Chemical reactions can proceed from reactants to products, which, if they are allowed to accumulate, will convert back to reactants.
b. The direction of reaction depends on concentrations and the collision of molecules.
5. Dynamic Equilibrium
a. When a reaction approaches dynamic equilibrium, the forward and reverse reactions proceed at equal rates.
b. There is no net change in concentrations.
c. Every reaction has its own characteristic ratio of products to reactants at equilibrium.
B. Metabolic Pathways
1. Molecules must be in sufficient concentration to permit reactions but low enough to prevent disruptive side reactions—for example, phenylalanine buildup in PKU.
2. Metabolic pathways form series of reactions that regulate the concentration of substances within cells by enzyme-mediated linear and circular sequences.
a. In degradative pathways, large molecules such as carbohydrates, lipids, and proteins are broken down to form products of lower energy. Released energy can be used for cellular work.
b. In biosynthetic pathways, small molecules are assembled into large molecules; for example, simple sugars are assembled into complex carbohydrates.
3. Participants in metabolic pathways are defined as follows:
a. Reactants are substances that enter reactions (= substrate = precursor).
b. Intermediates are the compounds formed between the start and the end of a pathway.
c. Enzymes are proteins that catalyze reactions.
d. Cofactors are small molecules and ions that help enzymes by carrying atoms or electrons.
e. Energy carriers are mainly ATP.
f. End products are the substances present at the conclusion of a pathway.

IV. Enzymes—Proteins With Catalytic Power
A. Characteristics of Enzymes and Their Substrates
1. Enzymes speed up reactions.
2. Enzymes can be reused.
3. Enzymes are very selective about the substrates to which they will bind and thereby bring about change.
4. Enzymes, at least some of them, can recognize both reactants and products in order to catalyze a reaction in both directions.
B. Enzyme Structure and Function
1. The active site is a crevice where the substrate binds to the enzyme during a reaction.
a. Emil Fischer (1890) thought of this matching as a lock-and-key fit.
b. More realistic is Koshland’s induced-fit model in which structural changes during binding allow a more precise fit.
2. Reactants must reach a “transition” state in order for a reaction to proceed.
a. Activation energy is the amount of energy needed to bring colliding molecules to the transition state.
b. Enzymes increase the rate of a reaction by lowering the activation energy through extensive bonding of substrate at the active site.
C. Effects of Temperature and pH on Enzymes
1. Because enzymes operate best within defined temperature ranges, high temperatures decrease reaction rate by disrupting the bonds that maintain three-dimensional shape (denaturation occurs).
2. Most enzymes function best at a pH near 7 (pepsin in the stomach is an exception); higher or lower values disrupt enzyme shape and halt function.
D. Control of Enzyme Activity
1. Some controls regulate the number of enzyme molecules available by speeding up/slowing down their synthesis.
2. Inhibitors can bind with an enzyme, or compete for the active site.
3. Allosteric enzymes have (in addition to active sites) regulatory sites where control substances can bind to alter enzyme activity; if this control substance is the end product in the enzyme’s metabolic pathway, feedback inhibition occurs.

V. Cofactors
A. Cofactors are nonprotein groups that bind to many enzymes and make them more reactive.
B. There are two main kinds of cofactors:
1. Coenzymes are large organic molecules such as NAD+ and NADP+ that transfer protons and electrons from one substrate to another.
2. Inorganic metal ions such as Fe++ also serve as cofactors when assisting membrane cytochrome proteins in their electron transfers in chloroplasts and mitochondria.

VI. Electron Transfers in Metabolic Pathways
A. Energy is released from storage molecules (such as glucose) in controlled steps via a series of intermediate molecules.
1. Electrons released during bond breaking are transferred stepwise through the components of electron transport systems located on various cell membranes.
2. Each time a donor gives up an electron it is oxidized; if it gains, it is reduced.
B. Electron transport systems are similar to staircases where electrons flow down the steps from the top (most energy) to the bottom (least energy), releasing a small amount at each step.
C. The energy is harnessed to move hydrogen ions, which in turn establish pH and electric gradients necessary for ATP production.

VII. ATP: The Universal Energy Carrier
A. Structure and Function of ATP
1. Before cells can use the energy of sunlight or that stored in carbohydrates, they must transfer the energy to molecules of ATP.
2. ATP is composed of adenine, ribose, and three phosphate groups.
3. ATP transfers energy to many different chemical reactions; almost all metabolic pathways directly or indirectly run on energy supplied by ATP.
B. The ATP/ADP Cycle
1. Energy input links phosphate to ADP to produce ATP.
2. ATP can donate a phosphate group (phosphorylation) to another molecule, which then becomes primed and energized for specific reactions.
3. ADP can be recycled to ATP very rapidly.