Essential Cell Biology 3rd ed: Ch3 Energy, Catalysis, and Biosynthesis

INTRO  

• To carry out the many chemical reaction needed to sustain a cell, a living organism requires both a source or atoms in the form of food molecules and a source of energy. Both of these things must come, ultimately, from the nonliving environment.

• Most of the chemical reactions that cells preform would normally occur only at temperatures that are much higher than those inside a cell. Because of this, each reaction requires a large boost in chemical reactivity for the reaction to occur within the cell. This boost is provided by enzymes, which will catalyze the chemical reaction to push the reaction forward, and tend to be connected in series to other reactions so that the product of one reaction becomes the starting material of the next. These long chemical reaction sequences are referred to as metabolic pathways.

• There are two opposing streams of chemical reactions that occur in cells

• Catabolic pathways- these break down foodstuffs into smaller molecules, gathering energy and some small building blocks that are needed for the cell.

• Anabolic pathways- (biosynthetic) use the energy harnessed by catabolism to drive the synthesis of the many molecules that form the cell.

THE USE OF ENERGY BY CELLS

• An organism's ability to maintain order is made possible by elaborate cellular mechanisms that extract energy from the environment and convert it into the energy stored in chemical bonds.

• Biological order is made possible by the release of heat energy from cells

• Entropy- the measure of a system's disorder.  

• Living cells are generating order and may appear to defy the second law of thermodynamics, but because a cell is not an isolated system, taking in energy from its environment to preform chemical reactions that release heat, they are still in compliance with the law

• This heat dispersed into the cell's surroundings is increasing the intensity of the thermal motions of the resident molecules, increasing the entropy of the system as a whole.

• Heat is energy in its most disordered form

• It is the tight coupling of heat production to an increase in order that distinguishes the metabolism of a cell form the wasteful burning of fuel in a fire.

• By directly linking the "burning" of food molecules to the generation of biological order- cells are able to create and maintain an island of order in a universe tending toward chaos. 

• The percentage of the different forms of energy will change as a result of the chemical reactions in the cell, as the overall amount of energy must still be the same, per the first law of thermodynamics. This conversion of chemical energy into heat energy is essential if the reactions inside the cell are to cause the universe as a whole to become more disordered- as required by the second law.

• Photosynthetic organisms use sunlight to synthesize organic molecules.

• Photosynthesis- a process that converts the electromagnetic energy in sunlight into chemical bond energy in cells. This is how solar energy enters the living world.

• Photosynthetic organisms are able to obtain all of the atoms they need from inorganic sources, such as the dirt or other non-living things around them. They then use the energy the derive from the sunlight to form chemical bonds between atoms, linking them into small chemical building blocks that will make up the plant.

• The reactions of photosynthesis will occur in two stages, one that is dependent on light and one that is not.

• In the light dependent stage, energy from sunlight is captured and transiently stored as a chemical bond energy in specialized small molecules that carry energy in their chemical groups. Molecular oxygen (O2) derived from the splitting of water by light is released as a byproduct of the first stage.

• In the second stage, the molecules that serve as energy carriers are used to help drive carbon fixation, in which sugars are manufactured from carbon dioxide gas (CO2) and water. This provides a stored chemical source of energy. 
• the over all reaction can be simplified as...

• Cells obtain energy by the oxidation of organic molecules

• In both plants and animals, energy is extracted from food molecules by a process of gradual oxidation, or controlled burning. To do this, the carbon and hydrogen atoms in the sugar and other organic molecules combine with oxygen (oxidation) to produce CO2 and H2O in a process known as cellular respiration.

• Photosynthesis and respiration are complementary processes. 

 

• Oxidation and reduction involve electron transfers

• The cell does not oxidize organic molecules in one step, through he use of enzyme catalysts metabolism carries the molecules through a large number of reactions that only rarely involve the direct addition of oxygen.

• Oxidation- this literally means the addition of an oxygen to a molecule, but generally, it means any case where electrons are removed from one atom and given to another. 

• Reduction-  is the addition of electrons to an atom.

• These two reactions will occur simultaneously.

• Oxidation/reduction reactions may even occur when there is only a partial shift in electrons. Ex. Polar covalent bonds.

• Hydrogenation reactions are reductions, and dehydrogenation reactions are oxidations.

• If the number of C-H bonds increases, its reduction. If the number of C-H bonds decreases, its oxidation.

FREE CATALYSIS

• Enzymes can speed up energetically favorable reactions- those that will later produce disorder- but they themselves can not force energetically unfavorable reactions.

• Enzymes lower the energy barriers that prevent chemical reactions from occurring.

• Free energy- (ΔG) energy that can be harnessed to do work or drive chemical reactions, and reflects a loss of orderliness.

• Chemical reactions proceed only in the direction that leads to a loss of free energy.

• Activation energy- the energy required to be added to the system to overcome an energy barrier before the chemical reaction can occur moving it to a lower energy (more stable) state. <-- this is what enzymes lower.

• Each enzyme binds tightly to one or two molecules, called substrates, and holds them in a way that greatly reduces the activation energy needed to facilitate a specific chemical interaction between them.

• Catalyst - a substance that can lower the activation energy of a reaction.

• These increase the rate of chemical reactions because they allow a larger percent of the random collisions with surrounding molecules to kick the substrates over the energy barrier.

• Enzymes are among the most effective catalysts know. Life could not exist without enzymes. 

• Every enzyme is a catalyst, but not every catalyst is an enzyme.

• Enzymes are highly selective, and usually only speed up one reaction out of the several possible reactions that could occur with the available substrate molecules.

•  Its selectivity comes from uniquely shaped active sites, so that only the right substrates will fit.

• After the reaction ALL catalysts -including enzymes- remain unchanged, and can function over and over again.

• The free-energy change for a reaction determines whether it can occur

• The change in free energy (ΔG) measures the amount of disorder created in the universe when a reaction takes place.

• If ΔG is negative;  then the reaction is energetically favorable, creating disorder by lowering the free energy of the system. 

• A reaction can only occur spontaneously if ΔG is negative.

• If ΔG is positive; then the reaction is energetically unfavorable, this reaction by itself would create more order, and therefor can not occur spontaneously.

• These reactions can only take place if they are coupled with a second reaction that has a negative ΔG large enough that the net ΔG of the entire process is negative.

• Enzymes also help with the coupling of these reactions

• The concentration of reactants influences the free-energy change and a reaction's direction.

• ΔG does not just depend on the energy stored in each molecule involved in the reaction, but also on the concentration of the molecules.

• Has to do with ratio percentages.

• The standard free energy change makes it possible to compare the energetics of different reactions.

• ΔG⁰- is the standard free energy change of a reaction, and is independent of concentration, instead it depends on the molecules behavior under ideal conditions where the concentrations of all reactants are set to 1mol/liter.

• ΔG =  ΔG⁰ + RT ln [x]/[Y]

• Where  ΔG is in kilocalories per mol, [Y] and [X] denote the concentrations of Y and X in moles per liter, and RT is the product of the gas constant and the absolute temperature.

• Cells exist in a state of chemical disequilibrium.

• Equilibrium - the point where the rates of the forward and reverse reactions are equal, and no further net change in the concentrations of the substrate or product is occurring.

• At equilibrium  ΔG is zero. At this point no reaction will occur and any cell that reaches the point of chemical equilibrium would be dead. This is because the maintenance of order within the cell requires continuous input of energy. To avoid this the cell is constantly exchanging materials with their environment.

• The equilibrium constant is directly proportional to  ΔG⁰.

• Equilibrium constant, K.

• K=[X]/[Y] 

• Where [X] is the concentration of the product and [Y] is the concentration of the reactant at equilibrium.

• In complex reaction, the equilibrium constant depends on the concentrations of all reactants and products.

• The same principle that is used above is used when two reactants combine to form a single product, except  the equilibrium constant now depends on the concentrations of both reactants and that of the product.

• K=[AB]/[A][B]

• The equilibrium constant indicates the strength of molecular interactions. 

• This free energy concept does not just apply to the breaking and forming of covalent bonds, it also applies to non-covalent bonds. Which are also very important to the cell, and include the binding of enzymes to the substrate

• Two molecules will bind to each other if the ΔG⁰ of the interaction is negative, resulting in a a complex that has a lower free energy that the sum of the free energies of the two partners when unbound.

• Because  ΔG⁰ is related directly to K, K is commonly used as a measure of the binding strength of a noncovalent interaction between two molecules, and can indicate how specific the interaction is between the two molecules.

• Binding energy - the energy released in the binding interaction.

• This will increase as K increases, so the larger the K is, the greater the drop in free energy between dissociated and associated states.

• For sequential reactions, the changes in free energy are additive

• A reaction with a positive  ΔG is not favorable, and will not happen unless an enzyme is used and the reaction is followed by another reaction that makes the sum of the  ΔG negative.

• Rapid diffusion allows enzymes to find their substrates.

• Rapid binding is possible because motions are enormously fast at the molecular level, due to heat energy.

• Diffusion- the idea that molecules are in constant motion and will explore the confined area by wandering randomly through it.

• The average distance that it travels from the starting point is proportional to the square root of the time it takes. So diffusion only works well for very short distances.

• Enzymes and other macromolecules do not move very easily through the cell though, and some are even held near where they are needed by scaffold proteins. And even if they are not held in place, they move so slow relative to the other small molecules in the cell that we view them as  stationary, and their effectiveness is dependent on the concentration of the substrate.

• When an enzyme and substrate have collided and snuggled together properly at the active site, they form multiple weak bonds with each other that persist until random thermal motion causes the molecules to dissociate again.

• These can include; hydrogen bonds, Vander Waals, and electrostatic attractions.

• Vmax and Km Measure enzyme performance

• The rate at which each enzyme functions varies greatly from one enzyme to another.

• This rate can be measured by mixing purified enzymes and substrates together under carefully defined conditions.

• Vmax- the point where the active sites of all enzymes molecules in the sample are fully occupied by substrate.

• At this point the rate of product formation only depends only on how rapidly the substrate molecule can be processed. This is referred to as the turnover number.

• Km- the concentration of the substrate needed to make the enzyme work efficiently is measured by Michaellis' constant, and referrers to the concentration of substrate at which the enzyme works at half its maximum speed (0.5Vmax).

• A low Km value will indicate that an enzyme binds very tightly to the substrate and a high value will show a weaker bond.

• When an enzyme lowers the activation energy of the reaction, it also lowers the activation energy of the reverse reaction by the same amount.

• Because of this the equilibrium point, and ΔG⁰, of the reaction will remain unchanged.

ACTIVATED CARRIER MOLECULES AND BIOSYNTHESIS

• The energy released by the oxidation of food molecules has to be temporarily stored before it can be used by the cell, and is usually stored in the form of a chemical bond in a small set of activated "carrier molecules".

• Active carriers store energy either as a readily transferable chemical group or as high-energy electrons. ATP, NADH, and NADPH are common examples of these.

• The formation of an activated carrier is coupled to an energetically favorable reaction.

• When a fuel molecule like glucose is oxidized in the cell, enzyme-catalyzed reactions ensure the a large part of the free energy released is stored in a chemically useful form. If it is not stored its released as heat.

• Coupled reaction- an energetically favorable reaction is used to drive an energetically unfavorable one, which produces and activated carrier or some other useful molecule.

• The amount of heat released by the oxidation of foodstuffs decreases by exactly the same about as the energy stored in covalent bonds.

• ATP is the most widely used activated carrier molecule

• This is the most important and versatile of the activated carriers.

• ATP is synthesized in an energetically unfavorable phosphorylation reaction, where a phosphate group is added to ADP (Adenosine 5'-diphosphate). ATP can then give up its stored energy through a hydrolysis reaction where the terminal phosphate is lost, converting it back to ADP.

 

• Phosphorylation is any reaction that involves the transfer of a phosphate group into a molecule, and is an example of condensation reactions. 

• This favorable release of energy is coupled with many unfavorable reactions, that would otherwise not occur.

• It can be used to supply energy for many of the pumps in the membrane, to power molecular motors, as well as many other uses.

• Energy stored in ATP is often harnessed to join two molecules together

• There can also be intermediate steps before getting to the desired product.

• The hydrolysis of ATP can be couple indirectly to push the reaction forward, by first forming an unfavorable intermediate product that can then undergo a favorable reaction to result in the desired end product.

• NADH and NADPH are important electron carriers

• Two common activated carriers that carry both high energy electrons and hydrogen atoms are NAD+ (nicotinamide adenine dinucleotide) and NADP+ (nicotinamide adenine dinucleotide phosphate). 

 

• Both of these pick up energy in the form of two high energy electrons plus a proton, becoming NADH (reduced nicotinamide adenine dinucleotide) and NADPH (reduced nicotinamide adenine dinucleotide phosphate). 
• the extra hydrogen will be added to the carbon directly across from the ringed nitrogen in the high lighted area shown above.

• NADPH is formed during a special set of energy yielding catabolic reactions, where a hydrogen atom and two electrons are removed from the substrate molecule and added to the nicotinamide ring of the NAPD+. This occurs through a typical redox reaction. 

 

• The hydride ion can then be readily given up in a similar redox reaction since the ring is actually more stable without the extra electrons.

• The extra phosphate group on NADPH is located far from the region involved in the transfer of electrons, but it gives the molecule a different shape (compared to NADH), making it possible for NADH and NADPH to bind as substrates to different sets of enzymes.

• The division of labor among the two carriers is because of the need to regulate two independent reactions.

• NADH is an intermediate is catabolic system of reactions that generate ATP. And NADPH is used with enzymes that catalyze anabolic reactions for syntheses of biological molecules.

• These two carriers are made through and regulated by different pathways

• The ratio of NAD+ to NADH is kept high, and the ratio of NADP+ to NADPH is kept low. So there is plenty of NADPH to act as a reducing agent, and NAD+ to act as an oxidizing agent.

• Cells make use of many other activated carrier molecules

• FADH2, like NADH also carries hydrogen and high energy electrons.

 

• Coenzyme A can carry an acetyl group in a transferable linkage (acetyl CoA) and can add two carbon units during the biosynthesis of the hydrocarbon tails of fatty acids.

Activated carrier	Group carried in linkage
ATP	Phosphate
NADH, NADPH, FADH2	Electrons and hydrogens
Acetyl CoA	Acetyl group
Carboxylated biotin	Carboxyl group
S-adenosylmethionine	Methyl group
Uridine diphosphate glucose	Glucose

• The synthesis of biological polymers requires an energy input

• Macromolecules make up the majority of the cells dry weight, and are made from monomers that are linked together during enzym-catalyzed condensation reactions.

• If none of these pathways provides a low enough  ΔG (ATP gives about -13kcal/mol) then AMP can be used at about -26kcal/mol