Energy and Metabolism

I.         Energy

            A.        Laws of thermodynamics

                        1.         Energy can be transferred and transformed but neither created nor destroyed

                        2.         Every energy transfer or transformation increases the entropy of the universe. Energy lost to entropy is usually in the form of heat (i.e., the random movement of particles). When we eat food we convert ordered forms of energy (carbohydrates, proteins, and lipids) into disordered forms (heat).

            B.        Free energy (G) - the portion of a system’s energy that is available to do work

                        1.         Two types of processes exist: spontaneous and nonspontaneous. Spontaneous reactions are those that occur without outside help and can be used to perform work. When spontaneous reactions occur, the system becomes more stable, and the entropy of the universe increases.

                        2.         Basic relationship is  order =  energy =  instability (or  stability) =  entropy

                        3.         Systems with high energy are unstable and prefer to lose that energy. The prefer to go from ordered to less ordered. To be spontaneous, free energy must be lost. The system must lose energy (decrease in H), gain entropy (increase in S), or both. When these two are added, ΔG must be negative.

                        4.         The greater the decrease in G, the more work can be done.

            C.        Types of reactions

                        1.         Exergonic reactions - have a net release of free energy. Energy is released and they proceed spontaneously.

                        2.         Endergonic - have a net gain of free energy. Energy is absorbed and so they do not proceed spontaneously - they must be forced.

            D.        Metabolic disequilibrium

                        1.         Work can be done when a system moves toward equilibrium. Work must be done on a system to move it away from equilibrium. Metabolic reactions are reversible and would reach equilibrium in vitro. A system at equilibrium has ΔG = 0 and can do no work.

                        2.         In order to remain alive, your cells need to avoid equilibrium - i.e., maintain metabolic disequilibrium.

            E.        Energy coupling

                        1.         Cells use exergonic processes to drive endergonic ones.

                        2.         ATP is the energy currency of the cell and consists of the nitrogen base adenine bonded to ribose and to 3 phosphates.

                        3.         The 3 phosphates make the molecule unstable and it prefers to get rid of one of them in the reaction ATP ➝ ADP + P. By doing so, energy is released and can be used to drive endergonic reactions.

                        4.         Enzymes transfer phosphates to other molecules, making them unstable. By getting rid of the phosphate (and, therefore, the energy), the phosphorylated molecule performs some kind of work.

                        5.         The reverse reaction, ADP + P ➝ ATP can be driven by the addition of energy. This energy is provided by cellular respiration.

II.        Enzymes

            A.        General

                        1.         Biological catalysts which are made of protein and speed up metabolic reactions by lowering activation energy so reactions can proceed at biological temperatures. Remember that, like all catalysts, the enzyme is not consumed during the reaction.

                        2.         Activation energy is energy required for reaction to proceed

                        3.         Often named for the substrate with the suffix “ase.” e.g., an enzyme which digests protein is a protease; one that digests lipids is a lipase.

            B.        Active site - the area of the enzyme where the reaction actually occurs. The active site is like a pocket into which the substrate fits. There is specificity between the enzyme and substrate because of the shape of the active site. “It’s all about shape, Baby!”

            C.        Substrate - usually only one substrate is ‘recognized’ by a given enzyme. The shape of substrate must match the shape of the enzyme active site.

            D.        ‘Induced Fit’ model - when substrate enters the active site, the shape of the site changes to induce a better fit between the substrate and the enzyme.

            E.        Cofactors - additional factors required for the enzyme to function; inorganic - e.g., Fe, Zn, K.

            F.        Coenzymes - additional factors required for the enzyme to function; organic - usually synthesized from vitamin precursors.

            G.        Factors affecting the rate of enzyme-catalyzed reactions:

                        1.         Temperature - (Fig 6.13) - as with non-catalyzed reactions, the reaction rate increases with increasing temperature because the kinetic energy of the molecules is greater and closer to the activation energy. Also, the increased molecular movement means more frequent collisions between molecules. This is advantageous for homeotherms because they can maintain body temperature close to the optimum temperature for enzymes. Why does enzyme activity decrease dramatically above a certain temperature?

                        2.         pH - (Fig 6.13) - a change in pH (i.e., [H⁺]) affects the tertiary structure of proteins. Because there is such high specificity between the active site and the substrate, if the shape of the active site changes, it will no longer match the substrate as well. Why does enzyme activity have an optimum pH?

                        3.         [S] - with increasing substrate, the enzyme spends less time “looking” for substrate and more time catalyzing reactions; Why does enzyme activity plateau at a certain [S]?

            H.        Enzyme regulation - to be efficient, the cell must be able to control enzyme activity.

                        1.         Inhibition - enzyme activity is slowed

                                    a.         competitive - an inhibitor binds to the active site, preventing the binding of substrate.

                                    b.         non-competitive - an inhibitor binds to a site other than the active site and causes a conformational change in the enzyme so the active site shape no longer matches that of the substrate.

                                    c.         allosteric - binding of an inhibitor to the “allosteric site,” (separate from the active site) causes a conformational change in all the active sites of that enzyme molecule.

                                    d.         feedback inhibition - an end-product from a chain of reactions is an inhibitor of an enzyme in the chain. This is an efficient way of building in self-regulation to a series of reactions.

                                                (1)       competitive - as above

                                                (2)       non-competitive - as above

                                                (3)       allosteric - as above

                        2.         Activation - enzyme activity is increased

                                    a.         allosteric - binding of an activator to the allosteric site improves the fit between substrate and active site.

                                    b.         precursor activity - a precursor of an enzyme’s substrate activates that enzyme. Think of this as a means of priming an enzyme to function more quickly when the substrate is about to be present.

                                    c.         cooperativity - the binding of substrate to one active site induces a favorable change in the shape of other active sites of that enzyme molecule; think of this as similar to allosteric activation.