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Enzyme Regulation, Bioenergetics, & Nucleic Acids

Enzyme Regulation, Bioenergetics, & Nucleic Acids -...

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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 : geneR protein- SLOW, IRREVERSIBLE 2. Zymogen activation : inactive proteins processed into active enzymes; pieces of polypeptide removed- IRREVERSIBLE 3. Regulatory enzymes - complex enzymes; REVERSIBLE 4. Covalent modification
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Zymogen Activation Zymogen Activation inactive precursor( zymogen ) R 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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Details 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 π-chymotrypsin ACTIVE 1 15 16 146 245 π- or α-chymotrypsin SS SS α-chymotrypsin ACTIVE 1 13 16 146 149 245 NOTE: dipeptides ser14-arg15 & thr147-asn148 removed
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Regulatory Enzymes Regulatory Enzymes Feedback Control Feedback Control Consider the conversion of thr to ile. E1 E2 E3 ………. thr y B y C y D y °° ° ile threonine threonine deaminase deaminase Final product ile inhibits first enzyme Final product ile inhibits first enzyme in pathway 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. Regulatory enzymes are complex & nearly always have quaternary structure.
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Threonine deaminase is an example of an allosteric regulatory allosteric regulatory enzyme enzyme Ile acts at site distant from the substrate binding site, causing the enzyme to undergo conformational change inhibiting the enzyme ile ile thr thr
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Allosteric Enzymes Allosteric 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, pyrimidine nucleotides feedback
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CTP inhibits ATCase CTP inhibits ATCase . Signal that more than sufficient CTP has been produced. Purines are synthesized by another metabolic pathway involving other reactions.
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