Chapter 8: Introduction to Metabolism Metabolism: all the chemical processes of an organism I) Anabolic pathways – consume energy to build complicated molecules from simpler ones(synthesis) II) Catabolic pathways – release energy by breaking down complex molecules to simpler compounds(decomposition)

Metabolic reactions may be coupled energy released from a catabolic reaction can be used to drive an anabolic reaction.

Kinetic vs. Potential Energy Kinetic energy – the energy of motion  Heat (thermal energy) is KE expressed in random movement of molecules  light Potential energy – energy that matter possesses because of its location or arrangement.  Chemical energy is PE sorted in molecules because of the arrangement of nuclei and electrons in atoms * An object on a hill or water behind a dam

Thermodynamics – study of energy transformation First Law of Thermodynamics  Energy can be transferred and transformed, but it cannot be created or destroyed. Second Law of Thermodynamics  Every energy transfer or transformation makes the universe more disordered (increases entropy)  Entropy is a quantitative measure of disorder that is proportional to randomness

Free Energy Free energy (G) is the portion of a system’s energy available to do work Free energy equation:  G =  H - T  S  G = change in free energy  H = change in total energy  S = change in entropy T = temperature(Kelvin)

What’s the significance of free energy? It indicates whether a reaction will occur spontaneously. A spontaneous reaction will occur without additional energy.

Exergonic reactions – a reaction that proceeds with a net loss of free energy [PROVIDES ENERGY] Endergonic reaction – an energy-requiring reaction that absorbs free energy from its surrounding [REQUIRES ENERGY]

Exergonic ReactionChem. - products have less free energy than reactants(decomposition) Spontaneous rxn and  G is negative Endergonic Reaction -products store more free energy than reactants(synthesis) Non-spontaneous rxn  G is positive In cellular metabolism, endergonic reactions are driven by coupling them to exergonic reactions.  ATP plays a critical role in this energy coupling

ATP (Adenosine Triphosphate): ATP is the immediate source of energy that drives most cellular work, which includes: Mechanical work – muscle contraction, cytoplasmic flow, chromosome movement during mitosis Transport work – pumping substances across membranes Chemical work – endergonic processes of polymerization

What type of macromolecule is ATP? ATP is a nucleotide with unstable phosphate bonds that the cell hydrolyzes for energy to drive endergonic reactions. Consists of:  Adenine, a nitrogenous base  Ribose, a five-carbon sugar  Chain of 3 phosphate groups

the terminal phosphate bond is hydrolyzed producing ADP (adenosine diphosphate). ATP + H 2 O  ADP + Phosphate + ENERGY!! The hydrolysis of the phosphate bonds is exergonic as the system shifts to a more stable state.

Regeneration of ATP:  The reaction is endergonic  driven by the exergonic process of cellular respiration

Enzymes  A chemical reaction will occur spontaneously if it releases free energy (-  G), but it may occur too slowly to be effective in living cells.  Biochemical reactions require enzymes to speed up and control reaction rates.

Catalysts are chemical agents that accelerate a reaction w/o being permanently changed in the process; they are recycled Enzymes are biological catalysts, which are usually proteins.

Before a reaction can occur, the reactants must absorb activation energy.  The transition state is the unstable condition of reactant molecules that have absorbed sufficient free energy to react.. Molecules react very slowly at cellular temperatures Enzymes allow reactions to occur at cellular temps by lowering the activation energy.

Substrate – The substance an enzyme acts on and makes more reactive  An enzyme binds to the substrate and catalyzes its conversion to product. The enzyme is released in original form. Active site – A region of the enzyme which binds to the substrate  Usually a pocket or groove on the protein’s surface What determines the specificity of an enzyme?  Three-dimensional shape of enzyme

Steps in the catalytic cycle of enzymes: 1-Substrate binds to the active site forming an enzyme-substrate complex. The substrate is held in the active site by chemical interactions (e.g. H-bonds and ionic bonds). 2-Side chains of a few amino acids in the active site catalyze the conversion of substrate to product. 3-Product departs active site and the enzyme emerges in its original form. Since enzymes are used over and over, they can be effective in very small amounts.

 Active site can hold two or more reactants in the proper position so they may react  Induced fit of the enzyme’s active site may distort the substrate’s chemical bonds, so less thermal energy (lower  G) is needed to break them during a reaction.  Active site might provide a micro-environment conductive to a particular type of reaction (e.g. low pH)

Temperature and pH Enzyme reaction rate increases with increasing temp.(to a point) Optimal pH range for most enzymes is pH 6-8.

Cofactors – small nonprotein molecules that are required for proper enzyme catalysis- called coenzymes if organic-may be active site residents, or just bind temporarily with substrate Enzyme Inhibitors Competitive inhibitors – chemicals that resemble an enzyme’s normal substrate and compete with it for the active site Noncompetitive inhibitors – enzyme inhibitors that do not enter the enzyme’s active site, but bind to another part of the enzyme molecule  Causes the enzyme to change shape so the active site cannot bind the substrate

Allosteric regulation Requires enzymes with allosteric sites- remote from the active site -A product of a pathway can shut down an enzyme in the pathway – this is feedback inhibition – ATP can act as a noncompetitive inhibitor yet AMP can allosterically activate the same enzyme as an activator

Cooperativity One substrate’s binding to an active site can prime the enzyme for additional substrate

So are inhibitors bad or good?  DDT – inhibits key enzymes in the nervous system  Penicillin – block active site of an enzyme that many bacteria use to build cell walls.