Bio Ch. 8

Feedback inhibition

A common mode of metabolic control, where a metabolic pathway is halted by the inhibitory binding of its end product to an enzyme that acts early in the pathway, e.g. the result of ATP allosterically inhibiting an enzyme in an ATP-generating pathway. Prevents a cell from making more of a substance than necessary, thus wasting chemical resources, by using the end product to block the beginning step in the pathway to make that product.

Enzyme localization

A team of enzymes in a particular metabolic pathway can assemble into a multi enzyme complex, facilitating the sequence of reactions, with the product from the first enzyme becoming a substrate for an adjacent enzyme in the complex, and so on until the end product is released. Some enzyme complexes have fixed locations and act as structural components. Others are in solution within membrane-enclosed eukaryotic organelles.

Allosteric regulation

Any case in which a protein's function at one site is affected by the binding of a regulatory molecule to a separate site; may result in inhibition or stimulation of an enzyme's activity. Behave like reversible noncompetitive inhibitors, changing an enzyme's shape and the functioning of its active site by binding to a site elsewhere on the enzyme.

Metabolic regulation

Cells can switch on and off the genes that encode specific enzymes and regulate enzyme activity once they've been made.

Thermal energy

Kinetic energy associated with the random movement of atoms or molecules. Heat is thermal energy in transfer from one object to another.

Chemical energy

Potential energy available for release in a chemical reaction. Biochemical pathways enable cells to release chemical energy from food molecules and use the energy to power life processes.

Conditions that affect enzyme activity

Temperature, pH, an chemicals that specifically influence that enzyme. Optimal conditions favor the most active shape for an enzyme. Temperature: Enzymatic reactions increase with increasing temperature up to a certain point. Above that temperature, enzymatic reaction speed drops sharply because the heat disrupts hydrogen bonds, ionic bonds, and other weak interactions that stabilize an enzyme's active shape, and eventually the enzyme denatures. Every enzyme has an optimal temperature at which its reaction rate is the greatest (for human enzymes this is about 35-40 °C, close to body temp.). pH: A pH of 6-8 is optimal for most enzymes. Environments that are too acidic or basic can denature proteins.

Kinetic energy

The relative motion of objects. Can perform work by imparting motion to other matter.

Potential energy

An object that is not presently moving (not kinetic). Energy that matter possesses because of its location or structure. Molecules possess energy because of the arrangement of electrons in the bonds between their atoms.

How ATP performs work

- ATP hydrolysis leads to heat production, and this heat and energy produced is harassed to perform the 3 types of cellular work. - Specific enzymes allow the cell to directly use energy released by ATP hydrolysis to drive chemical reactions that, by themselves, are endergonic. If the ΔG of an endergonic reaction is less than the amount of energy released by ATP hydrolysis, then the 2 reactions can be coupled so that, together, the 2 reactions are exergonic. This usually involves phosphorylation. - Phosphorylation is the transfer of a phosphate group from ATP to some other molecule, like the reactant; the recipient molecule binds covalently to the phosphate group and is called a phosphorylated intermediate, which is more reactive (less stable) than the original unphosphorylated molecule. - In transport work, ATP phosphorylates transport proteins, directly changing the protein's shape and ability to bind with other molecules. - In mechanical work, ATP binds noncovalently to motor proteins and then is hydrolyzed, releasing ADP and an inorganic phosphate. . The motor protein changes its shape and ability to bind to the cytoskeleton, resulting in movement of the protein along the cytoskeletal track.

ATP cycle

- ATP synthesis from ADP + inorganic phosphate requires energy; ATP hydrolysis to ADP + inorganic phosphate release energy. - Catabolism: break down reactions, exergonic, energy-releasing. - Cellular work: endergonic, energy-consuming. - Chemical potential energy stored in ATP drives most cellular work. - Occurs very rapidly. Is an overall endergonic reaction, not spontaneous; energy must be spent for the ATP cycle to occur. Energy coupling of exergonic and endergonic reactions. - ATP is a renewable resource that can be regenerated by the addition of phosphate to ADP. Reversible.

ATP structure

- Adenosine triphosphate (ATP) contains the sugar ribose with the nitrogenous base adenine and a chain of 3 phosphate groups bonded to it. - Used to make RNA and involved in energy coupling. - Bond between ATP phosphate groups can be broken by hydrolysis. A water molecule is used to break the terminal phosphate bond, causing a molecule of inorganic phosphate (HOPO3^2-, abbreviated as P with a circle around it subscript i) leaves the ATP, turning it into ADP (adenosine diphosphate). This is an exergonic reaction that releases 7.3 kcal of energy per mole (-7.3 kcal/mol) of ATP hydrolyzed under standard conditions. - Most reactions don't occur under standard conditions (because reactants and products differ from 1 M), and the actual ΔG is about 78% greater (-13 kcal). - The reactants ATP and H2O have high energy compared to the products they form.

Metabolic pathway

- Begins with a specific molecule, that's then altered in a series of defined steps, resulting in a certain product. Can have more than one starting molecule and/or product. - Each step of the pathway is catalyzed by a specific enzyme. - Two types: catabolic (degradative, breakdown, stored energy becomes available to do cellular work, e.g. cellular respiration) and anabolic (consume energy, build molecules, also called biosynthetic pathways, e.g. protein synthesis). Catabolic = "downhill"; anabolic = "uphill". - Energy released from reactions of catabolic pathways can be stored and used to drive reactions of anabolic pathways.

Endergonic reactions

- Energy inward. Absorbs free energy from its surroundings. Uses energy. Uphill. - G increases, ΔG is positive, nonspontaneous. - Magnitude of ΔG is the quantity of energy required to drive the reaction. - Energy often acquired from environment, e.g. plants using sunlight to drive photosynthesis (an exergonic reaction).

Exergonic reactions

- Energy outward. Has a net release of free energy. Downhill. - G decreases, ΔG is negative, occurs spontaneously. - The magnitude for this reaction represents the maximum amount of work the reaction can perform (note that some of the free energy is released as heat and can't do work). - The greater the decrease in free energy, the greater the amount of work that can be done. - E.g. cellular respiration: ΔG = -686 kcal/mol - The breaking of bonds doesn't release energy; it requires energy. So "energy stored in bonds" = potential energy that can be released when new bonds are formed after the original bonds break, as long as the products are of lower free energy than the reactants.

Activation energy barrier

- Every chemical reaction involves breaking AND forming bonds, e.g. hydrolysis involves adding an OH group to one molecule and an H to the other. - Usually a molecule must be contorted into a highly unstable state before a reaction can proceed; reactants do this by absorbing energy from their surroundings. When new bonds of the products form, energy is released as heat, and the molecules return to their stable shapes with lower energy. - Activation energy (free energy of activation, Ea): the initial investment of energy required for staring a reaction, i.e. the energy needed to control the reactants so the bonds can break. Often supplied by heat in the form of thermal energy. Thermal energy makes reactant molecules collided more often and forcefully, and it agitates atoms within molecules, making bonds more likely to break. - Transition state: unstable condition where molecules have absorbed enough energy for bonds to break. The peak of a free energy v.s. progress reaction graph. - The overall decrease in free energy means that Ea is repaid and then some, as the formation of new bond in the products release more energy than was invested the breaking of old bonds (ΔG < 0). - Activation energy provides a barrier that determines the rate of the reaction. - Heat can lower activation energy, but it denatures proteins and isn't molecule specific. This is why enzymes are ideal for catalyzing reactions. Enzymes don't change ΔG or make an endergonic reaction exergonic; they only hasten reactions that would occur anyway.

Second Law of Thermodynamics

- Every energy transfer or transformation increases the disorder (entropy) of the universe. Order can increase locally, but there's an unstoppable trend toward randomization of the universe as a whole. The entropy of a particular system (e.g. an organism) may decrease as long as the total entropy of the universe (i.e. the system plus its surroundings) increases. - Some energy becomes unavailable to do work during every energy transfer or transformation. More usable forms of energy typically at least partly converted to thermal energy and released as heat, which dissipates rapidly into the surroundings. - The loss of usable energy as heat to the surroundings means that every energy transfer or transformation makes the universe more disordered. Scientists use a quantity called entropy as a measure of disorder, or randomness. The more randomly arranged a collection of matter is, the greater its entropy. - Entropy in the universe takes the form of increasing amounts of heat and less ordered forms of matter. - In most ecosystems, energy enters in the form of light and exits in the form of heat. - Organisms increase the entropy of their surroundings. They both create ordered structures from less organized starting materials and take in organized forms of matter and energy and replace them with less ordered forms. - Spontaneous process: if a given process, by itself, leads to an increase in entropy, that process can proceed without requiring an input of energy; the process is energetically favorable. Some may be spontaneous (e.g. an explosion) or much slower (e.g. rusting). - Nonspontaneous process: a process that, considered on its own, leads to a decrease in entropy; it'll only happen if energy is supplied. Since some heat is lost in nonspontaneous reactions as well, the process leads to an increase in entropy in the universe as a whole.

Free-energy change, ΔG

- Gibbs free energy system (without considering its surroundings), symbolized by the letter G. This is referred to as free energy. ΔG represents the change in free energy. - Free energy: the portion of a system's energy that can perform work when temperature and pressure are uniform throughout the system, as in a living cell.

Enzyme inhibitors

- Inhibitors can attach to an enzyme by covalent bonds; this is usually irreversible, e.g. toxins and poisons. Most bind to an enzyme by weak interactions, though, and are reversible. - Competitive inhibitors: reversible inhibitors that resemble the normal substrate molecule and compete for admission into the active state. Mimics substrate. Reduce enzyme productivity by blocking substrates from entering active sites. Can be overcome by increasing substrate concentration. - Noncompetitive inhibitors: don't directly compete with the substrate to bind to the enzyme at the active state, but instead impede enzymatic reactions by bidding another part of the enzyme, altering the enzyme's shape so that the active site functions less effectively, if at all. - Enzyme inhibitors: pesticides, antibiotics.

Allosteric activation and inhibition

- Most allosterically regulated enzymes are made from 2 or more subunits, each with its own active site. The complex oscillates between 2 different shapes, one catalytically active and the other inactive. Shape change in one subunit is transmitted to all others. - In the simplest allosteric regulation, an activating or inhibiting regulatory molecule binds to a regulatory site (allosteric site), often located where the subunits join. The binding of an activator to a regulatory site sterilizes the shape that has functional active sites, while the binding of the inhibitor stabilizes the inactive form of the enzyme. - E.g. ATP lowers an enzyme's substrate affinity and acts as an inhibitor; ADP acts as an activator. - Cooperativity: a substrate molecule binding to one active site in a multisubunit enzyme triggers a shape change in all the subunits, thus increasing catalytic activity at the other active sites. Amplifies response of enzymes to substrates. One substrate primes an enzyme to act on additional substrate molecules more readily. Substrate affinity increases as more sites are filled. Release of a substrate decreases substrate affinity.

How the active site works

- R groups of a some of the amino acids in the active site catalyze the conversion of substrate to product. - A singel enzyme acts on about a thousand substrate molecules per second. - Enzymes emerge from the reaction in their original form. - Enzymes can catalyze the forward or the reverse part of metabolic reactions, since these reactions are reversible, but it depends on which direction has a negative ΔG, which depends mainly on the relative concentration of reactants and products. The net effect is always in the direction of equilibrium. - An enzyme's active site may stretch substrate molecules word their transition-state form, stressing and bending chemical bonds that must be broken. Ea is proportional to the difficult of breaking bonds. The enzyme help lower the amount of free energy a substrate needs to achieve the transition state. - Enzymes can also make the environment more conducive to a particular reaction (e.g. having acidic R groups). - Amino acids in the active side directly participate in the chemical reaction, such as by covalently bonding their side chains to the substrate. - Greater concentration of substrate molecules means they access enzymes' active sites more, meaning reactions occur more quickly. When a substrate concentration is high enough that all enzymes' active sites are occupied, then the enzyme is saturated; the only way to increase reaction speed is to addd more enzymes.

Reactions and equilibrium

- Reactions in an isolated system eventually reach equilibrium and can no longer do work. Chemical reactions that are reversible, such as metabolism, also reach equilibrium they occur in isolation. - Since, at equilibrium, G is at a minimum and no work can be done, a cell is dead! - The constant flow of materials in and out of a cell prevents its metabolic pathways from reaching equilibrium. - Catabolic pathways in cells release free energy in a series of steps. The key to maintaining a lack of equilibrium is having the product of a reaction not accumulate but become a reactant in a next step; waste products are expelled from cells. - Free-energy differences keep the sequence of reactions going.

Enzymes

- Substrate: the reactant an enzyme acts on. - Enzyme-substrate complex; formed when a enzyme binds to its substrate(s). - When in contact, enzymes convert substrates to different product(s). - Enzyme + substrate(s) = enzyme-substrate complex = enzyme + product(s) - Most enzyme names end in -ase. - Active site: the region of the enzyme that binds to the substrate. On the enzyme's surface. There's a complementary fit between an enzyme's active site and the shape of its substrate. - Induced fit: the enzyme changes its shape slightly when in the enzyme-substrate complex, allowing additional weak bonds (such as hydrogen and ionic) to form and letting the active site enfold the substrate and hold it in place. The fit between enzyme and substrate becomes higher after initial contact and brings chemical groups of the active site not positions that enhance their ability to catalyze the chemical reaction.

First Law of Thermodynamics

- The energy of the universe is constant: Energy can be transferred and transformed, but it cannot be created or destroyed. - Also known as the principle of conservation of energy.

Free energy, stability, and equilibrium

- ΔG represents the difference between the free energy of the final state and the free energy of the initial state: ΔG = G(final state) - G (initial state). Thus ΔG can only be negative if a process involves a loss of free energy during the change from the initial state to the final state. Less free energy means the system is less likely to change and is more stable. - Free energy is a measure of a system's instability. Unstable systems (higher G) tend to change to become more stable (lower G). - Equilibrium is a state of maximum stability. Chemical equilibrium means back and forth reactions are occurring at the same rate, with no net change in the relative concentration of reactants and products. Free energy decreases as a chemical reaction approaches equilibrium and increases when its pushed away from equilibrium. - For a system at equilibrium, G is at the lowest possible value in that system. Any change from the equilibrium position will have a positive ΔG and not be spontaneous, so systems never spontaneously move away form equilibrium. Since a system at equilibrium can't spontaneously change, it can do no work. - A process is spontaneous and can perform work only when it's moving toward equilibrium.

3 types of cellular work

Chemical work: the pushing of endergonic relations that wouldn't occur spontaneously, such as the synthesis of polymers from monomers. Transport work: the pumping of substances across membranes against the direction of spontaneous movement. Mechanical work: such as the beating of cilia, the contraction of muscle cells, and the movement of chromosomes.

Cofactors

Nonprotein enzyme helpers that aid catalytic activity. May be tightly bound to an enzyme permanently, or bound loosely and reversibly with a substrate. Some are inorganic. Organic cofactors specifically are called coenzymes, e.g. vitamins.

Energy

The capacity to cause change. Some forms can be used to do work (i.e. move matter against opposing forces, like gravity and friction). The ability to rearrange a collection of matter. Exists in various forms. A small amount of energy is usually lost as heat, sometimes because of friction.

Bioenergetics

The study of how energy goes through living organisms.

Thermodynamics

The study of the energy transformations that occur in a collection of matter. System = the matter under study. Surroundings = everything outside the system, the rest of the universe. Isolated system = unable to exchange either energy or matter with its surroundings. Open system = energy and matter can be transferred between the system and its surroundings

Metabolism

The totality of an organism's chemical reactions. Manages the material and energy resources of the cell.

Energy coupling

The use of an exergonic process to drive an endergonic one. ATP is responsible for most energy coupling in cells and often acts as the immediate source of energy that power cellular work.

ΔG equation

ΔG = ΔH - TΔS ΔH = the change in the system's enthalpy (equivalent to the total energy in biological systems). ΔS = the change in the system's entropy T = the absolute temperature in Kelvin (K) units Can be used to predict whether the process will be spontaneous or not. Spontaneous reactions require no input of energy. Only processes with a negative ΔG are spontaneous. For ΔG to be negative, ΔH must be negative (the system gives up enthalpy and H decreases) or TΔS must be positive (the system gives up order and S increases), or both: When ΔH and TΔS are tallied, ΔG ahas a negative value (ΔG < 0) for al spontaneous processes, meaning spontaneous reaction decreases the system's free energy. Processes that have a positive or zero ΔG are never spontaneous.