Metabolism the biochemical reactions that occur within a living organism and the energy exchanges and transformations that accompany them Catabolism - Anabolism - Trophic Strategies - Autotrophs - synthesize cellular constituents from simple molecules Heterotrophs - obtain free energy from the oxidation of organic compounds are are ultimately dependent on autotrophs

Nutritional Requirements

Building or breaking down a wide range of molecules through conversion to common intermediates

5 Common Characteristics of Metabolic Pathways 1. Metabolic Pathways are Irreversible 2. Every Pathway has a First Committed Step 3. Catabolic and Anabolic Pathways Differ 4. All Metabolic Pathways are Regulated 5. Pathways Occur in Specific Locations

Thermodynamics and Enzymes - Again First Two Laws of Thermodynamics 1. Energy can not be created or destroyed but it may change forms The energy in the universe remains constant 2. In all natural processes, the entropy of the universe increases "First: "You can't win.” Second: "You can't break even.” Third: "You can't quit the game.” AP Snow

Thermodynamics and Enzymes - Again Gibbs Free Energy (  G) Amount of energy capable of doing work *remember -  G indicates that the reaction can occur without the input of energy. It DOES NOT indicate that the reaction will occur at a measureable rate.  G is a state function.

Thermodynamics and Enzymes - Again Gibbs Free Energy (  G) Can be calculated from equilibrium concentrations dependent on both substrate and product concentrations (gas entropy example)  G =  G 0’ + RTln [C] c [D] d [A] a [B] b  G =  G 0’ + RTlnK eq At equilbrium  G = 0  G 0’ = -RTlnK eq K eq = e  G0-/RT  G 0’ - standard state R - gas constant T - temperature

Thermodynamics and Enzymes - Again Enzymes 1. Alter the rate of a reaction 2. Lower the transition state for the forward and reverse reactions 3. Only function in a reaction that would occur without it Spontaneous reactions (negative  G) 4. Are unchanged

Thermodynamics and Metabolism Near equilibrium reactions -  G is close to zero Far from equilibrium reactions - very large negative  G

Thermodynamics and Metabolism Flux of reactions or rate of flow Near equilibrium - Far from equilibrium - Implications of far from equilibrium 1. Metabolic pathways are irreversible 2. Every metabolic pathway has a first committed step 3. Catabolic and anabolic pathways differ.

Control of Flux J = Vf-Vr (flux is equal to the rate of the forward rxn minus the rate of the reverse) For the pathway as a whole the flux is determined by the rate limiting step

Mechanisms to Control of Flux 1. Allosteric control 2. Covalent modifications 3. Substrate Cycles 4. Genetic Control

5. Metabolic Pathways Occur in Specific Cellular Locations In multicellular organisms, tissue specific reactions also occur

Enzymes Catalyze Metabolic Reactions 4 major types of reactions 1. Oxidations and reductions - oxidoreductases 2. Group transfer reactions - transferases and hydrolases 3. Eliminations, isomerizations and rearrangements - isomerases and mutases 4. Making or breaking Carbon bonds - hydrolases, lyases and ligases

Models of C—H bond breaking.

Group Transfer Reactions Transfer of an electrophilic group from one nucleophile to another. Y: + A - X Y - A + X: Acyl Group Transfers chymotrypsin Phosphoryl Group Transfers hexokinase Glycosyl Group Transfers lysozyme

High Energy Compounds - Free Energy Currency 1. ATP and phosphoryl group transfer

Different ways the cells utilize the high energy bonds in ATP Coupling endergonic and exergonic reactions Phosphate group transfers Inorganic pyrophosphatase (ATP yields AMP + PPi)

NTPs are freely interconverted ATP + NDP ADP + NTP Nucleoside diphosphate kinase Different ways the cells utilize the high energy bonds in ATP ATP binding and hydrolysis alters conformation Glycogen phosphorylase - (active)

Other phosphorylated compounds and regeneration of ATP Substrate level phosphorylation Oxidative phosphorylation

Oxidation - Reduction Reactions Involve the loss or gain of electrons most biochemical involve C-H bond cleavage with loss of two bonding electrons by carbon usually transferred to electron acceptor (carrier) NAD+, FADH+

Oxidation - Reduction Reactions Involve the loss or gain of electrons reduction potential - how strongly a compound attracts electrons (larger value, stronger attraction)

Eliminations, Isomerizations and Rearrangements 1. Eliminations - formation of a double bond between two saturated single-bonded centers Ex. Enolase, fumerase 2. Isomerizations - change in location of double bond intramolecular shift of hydrogen atom Ex. Phosphoglucose isomerase

Eliminations, Isomerizations and Rearrangements 3. Rearrangements break and reform C-C bonds in a way that rearranges the carbon skeleton few Ex. Methylmalonyl CoA mutase (oxidation of odd chain fatty acids)

Reactions that make and break Carbon Bonds Many different mechanisms for you organic fans these include aldol condesations, (aldolase in glycolysis), Claisen condensations (citrate synthase in TCA cycle), and decarboxylations We will look at specific mechanisms as we study the pathways

AVG = St dev = 2538 High = 196, low = , % and above (min 450 total course pts) = A (min 430 pts) = A (min 390 pts) = B (min 370 pts) = B (min 340 pts) = B (min 310 pts) = C+ Grad A = > 850 pts A- = >775 pts B+ = > 725 pts B = > 650 pts B- = > 550 pts C+ = > 500 pts