L30-32 - 1 1 Biochemistry Sixth Edition Chapter 10:...

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Unformatted text preview: 1 1 Biochemistry Sixth Edition Chapter 10: Regulatory Strategies Berg Tymoczko Stryer 2 TrafFc needs to be controlled by trafFc signals. Biological pathways need to be controlled by certain signals too! eedback Inhibition Product (CTP) inhibits the commitment step ( i.e. Frst CTP-speciFc) of a multi-step complex process 3 ive principal ways of controlling enzymatic activity 1. Allosteric control--Binding of a small molecule (often an enzymes product) at regulatory site (NOT active site) changes enzyme activity; this is an example of cooperativity. e.g. aspartate transcarbamoylase (ATCase). 2. Multiple forms of enzymes--Isozymes, or isoenzymes. Vary slightly in structure; vary in K M and V max . 3. Reversible covalent modiFcation-- e.g. phosphorylation of protein kinase A (PKA) to control its activity. 4. Proteolytic activation--Irreversibly activates inactive enzyme precursors ( zymogens, or proenzymes ). e.g. generation of digestive enzymes (chymotrypsin, trypsin, pepsin); e.g. generation of blood clotting factors. 5. Controlling the amount of enzyme present at level of transcription and translation (Chpt 31) * 2 4 10.1) Aspartate transcarbamoylase is allosterically inhibited by the end product of its pathway many steps in pyrimidine biosynthesis 1 st committed step in pyrimidine biosynthesis The product of pyrimidine biosynthesis: a pyrimidine! 5 CTP inhibits ATCase example of feedback inhibition High [product] leads to low rate Keeps ATCase from needlessly making more CTP Cooperativity Is Negative and Heterotropic low rate (not zero, however) high [product] 6 Allosteric enzymes often display sigmoidal kinetics cooperativity allows large change in rate over a narrow range of substrate concentration Cooperativity Is Positive and Homotropic 3 7 ATCase consists of multiple polypeptide chains Polypeptide chains are held together by disulFde bonds Can be broken by p-hydroxymercuribenzoate 8 Ultracentrifugation of native and mercurated ATCase native mercurated p-mercuribenzoate groups can be displaced by adding excess of -mercaptoethanol to displace the Hg c is for catalytic subunit-- has three 34 kd chains; displays non-sigmoidal, Michaelis-Menten kinetics in absence of r subunit; does not bind CTP r is for regulatory subunit--has two 17 kD chains; no enzymatic activity; binds CTP 3 2 9 Structure of ATCase: 2c 3 + 3r 2--> c 6 r 6 Zn 2+ is bound to 4 cysteines Is why mercuration disrupts ATCase (=r 2 ) (=c 3 ) LIVING IGURE 4 10 PALA is a bi substrate analog that mimics a high-energy, oxyanion intermediate of ATCase compare these * 11 PALA binds at an active site composed of two chains * Catalytic trimer has 3 active sites (green, brown, yellow)....
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This note was uploaded on 07/23/2008 for the course CHEM 476 taught by Professor Bevilacqua,philip during the Fall '07 term at Pennsylvania State University, University Park.

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L30-32 - 1 1 Biochemistry Sixth Edition Chapter 10:...

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