Chapter 16 Introduction to Metabolism Metabolism = the sum of all chemical reactions that take place in a cell or organism. Bioenergetics = the quantitative study of the energy transductions that occur in in living cells and the nature and function of the chemical processes underlying these transductions.
Catabolic pathways generally converge • Anabolic pathways diverge • Some pathways are cyclic
Overview of catabolism Complex Monomeric unit
Glycolysis Learn to draw this pathway with structures
A Metabolic “Map” Acetyl-CoA plays central role
Acetyl-Coenzyme A Learn to recognize this molecule
Principles of Metabolic Regulation • General features of metabolic pathways: • Individual reaction steps may be reversible, but the overall pathway is irreversible. • The irreversible committed step is usually an early reaction step. (DG1 << 0) • The rate of metabolism (flux) through a pathway is regulated at the committed reaction step (rate-limiting step). • Opposing degradation/biosynthetic pathways that proceed through the same metabolites must differ in at least one enzyme to allow for independent regulation in each direction. (Often referred to as “coordinated control” or “reciprocal regulation”.) • The enzymes that mediate a given reaction pathway are found in the same cellular compartment or organelle.
Glycolysis The irreversible committed step is usually an early reaction step. (DG1 << 0)
The enzymes that mediate a given reaction pathway are found in the same cellular compartment or organelle
II. How are reaction steps regulated? A. Enzyme amount (esp. procaryotes) 1. Transcription 2. Translation 3. mRNA stability 4. Protein stability (degradation) B. Enzyme activity (positive or negative effectors) 1. Metabolites 2. Active site inhibitors 3. Allosteric modulators 4. [ATP]/[ADP] energy status 5. [NADH]/[NAD+] reduction status 6. Covalent modification of enzyme (phosphorylation)
Regulation by metabolites within the same pathway • Simple feedback inhibition • Complex feedback inhibition • 1. Cumulative • 2. Concerted • 3. Sequential • 4. Isoenzymes for multiple effectors
Biological Systems Obey the Physical Laws of Thermodynamics DG = DH - TDS DH = DU + PDV G = Gibbs Free Energy H = Enthalpy S = Entropy U = Internal Energy
c d [C] [D] D D G = G' + RT ln o [A] [B] a b Free Energy Calculations: Standard free E change at pH 7 Biochemists use this DG < 0, product formation is favored DG = 0, reaction at equilibrium DG > 0, substrate formation favored At equilibrium, If all [i] = 1 M, Standard free E change under standard conditions pH 0, 1 atm pressure & When recatants & products are present initially at 1 M
Living systems can couple energy requiring reactions to those which are spontaneous (exergonic)
Some coupled reactions involving ATP Exergonic reaction drives the endergonic processes
Adenosine triphosphate (ATP) Learn to draw the structure of ATP High-energy bonds
ATP is kinetically very stable ATP + H2O Slow reaction ADP + HPO42- Garrett & Grisham Fig. 3.8 ATP in water is not readily converted to ADP, but needs enzymes to mediate hydrolysis.
ATP the universal energy carrier It releases a significant amount of free energy upon hydrolysis. But not too much so it can be a between “high energy” phosphate donors and low energy acceptors.
Why are the hydrolysis products (ADP+Pi) more stable than the reactant (ATP)? (1) More resonance forms per phosphate in hydrolysis products ATP * More possible forms a molecule can exist stabilizes the molecule * Pi has more resonance forms than ATP ADP Pi (2) Charge separation in products Similar electrostatic charges close together in ATP compared to products
Hydrolysis of energy rich compound can form an unstable compound but can isomerize spontaneously to form stable compund Stable form Spontaneous isomerization
1) Calculate the equilibrium constant for the hydrolysis of glucose-1-phosphate at 37oC. From table DGo’ = - 20.9 kJ.mol-1 @ equilibrium DG = 0 Answer: K = 3300 K