L19 - Enzyme Regulation Topics Enzyme Regulation Levels of...

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Unformatted text preview: Enzyme Regulation Topics Enzyme Regulation Levels of Metabolic Regulation Regulation by Substrate Concentration (V & K ) max m Regulation by Inhibition Allostery and Feedback Inhibition Regulation by Covalent Modification 1 The Important (Exam) Stuff Explain the need to regulate enzyme activity. Describe how a cell achieves shortterm and long term metabolic regulation. Define V and K and explain how substrate max m concentration can regulate enzyme activity. Describe competitive and noncompetitive inhibition and their effects on enzyme V and K . max m Explain allostery and feedback inhibition. Describe regulation by covalent modification. Levels of Regulation Regulate enzyme activity substrate product translation transcription Why? Regulate enzyme synthesis Enzyme A Enzyme B No enzyme No mRNA Translation Transcription Gene A Gene B Gene C Gene D Response, Coordination & Conservation 2 Regulation of Enzymes by Substrate Concentration Initial Velocities 3 Concentration Profiles More Enzyme More Product Faster V i Same Km Effect of Enzyme Dilution 4 Significance of K m Small values = high affinity Large values = low affinity Simple enzyme systems show the largest changes in activity for the smallest change in substrate concentration around the K value m K provides a rough estimate of m substrate concentration in the enzyme's environment. Useful tool for comparing affinities of different enzymes for same substrate (and vice versa). Competitive Inhibitors No inhibitor 2x V i 1x K K m(app) m [S] Competitive inhibitors interact at the same binding site as the substrate for the enzyme (mutually exclusive binding). Competitive inhibitors increase K , but do not affect V . m max Competitive inhibitors can be "deadend" compounds (analogs) as well as alternative substrates. Competitive inhibition can be overcome by high [substrate]. 5 Competitive Inhibition and Regulation of Krebs Cycle FADH 2 Noncompetitive Inhibition No inhibitor V 1x 2x K m [S] Noncompetitive inhibitors interact at a binding site distant and different from the substrate binding site Noncompetitive inhibitors do not decrease K but DO m decrease V ! max Noncompetitive inhibition is not influenced by [substrate]. 6 Feedback Inhibition Noncompetitive inhibition Simple Allosteric Enzymes Enzymes subject to metabolic regulation are often allosteric. Allostery means "different shape". Activity of enzyme is changed by binding of effector molecules. Positive effectors increase activity Negative effectors decrease activity o Often occurs in enzymes with 4 with multlple active sites. Example: One holoenzyme can bind >1 substrate molecule. 7 The Benefits of Allostery Allows for positive and negative regulation of enzyme activity regardless of substrate concentration. Cooperative binding allows strong regulation over narrow range of substrate concentrations. Feedback Inhibition and Allosteric Control Aspartate + Carbomyl P Pyrimidines (CTP,TTP) ACTase X,Y,Z Purines (ATP, GTP) Generate Sigmoidal Curve Unlike either competitive or noncompetitve inhibition Bind to noncatalytic site Like noncompetitive inhibition Change Km Like competitive Inhibition 8 ACTase: An Allosteric Enzyme Separate subunits for catalysis and regulation Low Activity Catalytic sites Regulatory sites High Activity LARGE changes in quaternary structure Covalent Modification The reversible addition of small molecules via covalent bonding to specific amino acids regulates enzyme activity. This form of post translational modification allows rapid enzymatic response to changes in the cell's environment. Small molecules used for covalent modification include: PO4 (phosphorylation) CH3, C2H5 (methylation, acetylation) AMP (adenylylation) 9 Text References th Pages 205209 (11 Edition) 10 ...
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