Regulation - *Regulation of Enzyme Systems* *Regulation...

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*Regulation of Enzyme Systems* *Regulation of Enzyme Systems* Metabolic systems are controlled by regulating some of their enzymes. Types of Regulation Types of Regulation 1. Control of gene expression : gene F protein- SLOW, IRREVERSIBLE 2. Zymogen activation : inactive proteins processed into active enzymes; pieces of polypeptide removed- IRREVERSIBLE 3. Regulatory enzymes - complex enzymes; REVERSIBLE
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Zymogen Zymogen Activation Activation inactive precursor( zymogen ) F ACTIVE - at cellular level " zymogen granules (full of zymogen proteins) At the molecular level: At the molecular level: Pepsinogen pepsin Trypsinogen trypsin Chymotrypsinogen chymotrypsin
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etails of Chymotrypsinogen Activation: zymogen = chymotrypsinogen processed by the pancreas with chymotrypsin secreted into the intestines. Chymotrypsinogen is a single polypeptide of 245 aa residues. The active product is sometimes called α -chymotrypsin
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Chymotrypsinogen SS SS INACTIVE 1 15 146 245 trypsin SS SS -chymotrypsin ACTIVE 1 15 16 146 245 π -or α -chymotrypsin SS SS α -chymotrypsin ACTIVE 1 13 16 146 149 245 OTE: dipeptides ser14-arg15 & thr147-asn148 removed
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Regulatory Enzymes Regulatory Enzymes Feedback Control Feedback Control onsider the conversion of thr to ile. E1 E2 E3 ………. thr F B F C F D FFFF ile threonine threonine deaminase deaminase 1 st enzyme (E1) Final product ile inhibits first enzyme in pathway
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Feedback Inhibition Feedback Inhibition Last or near last product of synthetic pathway inhibits the first enzyme in pathway. efficient common regulatory enzyme. egulatory enzymes are complex & nearly always have quaternary structure.
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Threonine deaminase is an example of an allosteric allosteric regulatory regulatory enzyme enzyme ile thr Ile acts at site distant from the substrate binding site, causing the enzyme to undergo conformational change inhibiting the enzyme
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Allosteric Allosteric Enzymes Enzymes 1. Complex, multimeric 2. Several binding sites Catalytic sites-- substrate Regulatory sites -- inhibitory or activator -- sometimes several sites of each type 3. Conformational change 4. Not obey Michaelis-Menten kinetics
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G enerally, for an allosteric enzyme, rate(v) vs [S] is sigmoidal sigmoidal instead of hyperbolic. Simple enzyme = hyperbolic: at low [S], activity fairly high Complex, allosteric = sigmoidal: activity low at low [S], increases greatly in midrange Efficiency is better, more responsive to [S] [S] v sigmoidal
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Example : aspartate transcarbamoylase = ATCase O O UTP H 2 N + C-NH 2 HN-C-NH 2 TTP, asp O asp CTP CTP OPO O carbamoyl carbamoyl aspartate phosphate Pyrimidines and purines are needed for RNA and DNA synthesis pyridine nucleotides feedback
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Regulation - *Regulation of Enzyme Systems* *Regulation...

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