enzymes: regulatorychemistry.creighton.edu/~jksoukup/lec10.pdf · enzymes: regulatory regulatory...

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Enzymes: Regulatory Regulatory enzymes In a metabolic pathway, which utilizes numerous enzymes, a regulatory enzyme sets the rate of the overall sequence because it catalyzes the slowest, rate-limiting reaction Characteristics of regulatory enzymes Allosteric control Use of binding proteins Reversible covalent modifications Proteins kinases and phophatases Proteolytic activation

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Page 1: Enzymes: Regulatorychemistry.creighton.edu/~jksoukup/lec10.pdf · Enzymes: Regulatory Regulatory enzymes In a metabolic pathway, which utilizes numerous enzymes, a regulatory enzyme

Enzymes:Regulatory

Regulatory enzymesIn a metabolic pathway, which utilizes numerous enzymes, a regulatoryenzyme sets the rate of the overall sequence because it catalyzes theslowest, rate-limiting reaction

Characteristics of regulatory enzymesAllosteric controlUse of binding proteinsReversible covalent modifications

Proteins kinases and phophatasesProteolytic activation

Page 2: Enzymes: Regulatorychemistry.creighton.edu/~jksoukup/lec10.pdf · Enzymes: Regulatory Regulatory enzymes In a metabolic pathway, which utilizes numerous enzymes, a regulatory enzyme

Enzymes:Regulatory

Allosteric enzymesInvolve reversible noncovalent binding of regulatory compounds calledallosteric modulators

Binding of modulators can be inhibitory or stimulatoryBinding of modulator causes conformational changes

catalytic regulatory

Page 3: Enzymes: Regulatorychemistry.creighton.edu/~jksoukup/lec10.pdf · Enzymes: Regulatory Regulatory enzymes In a metabolic pathway, which utilizes numerous enzymes, a regulatory enzyme

Enzymes:Regulatory - Allosteric enzyme

Aspartate transcarbamoylase (ATCase)Feedback control by production of end product of pathway

Allosteric inhibition - CTP inhibits aspartate transcarbamoylase bybinding to a regulatory site (not an active site)

Page 4: Enzymes: Regulatorychemistry.creighton.edu/~jksoukup/lec10.pdf · Enzymes: Regulatory Regulatory enzymes In a metabolic pathway, which utilizes numerous enzymes, a regulatory enzyme

Enzymes:Regulatory - Binding proteins

Trypsin can be bound by trypsin inhibitor (BPTI) and inactivated

Protease inhibitors are common in nature~10% of blood plasma proteins are protease inhibitorsA mutant of one protease inhibitor causes emphysema

Page 5: Enzymes: Regulatorychemistry.creighton.edu/~jksoukup/lec10.pdf · Enzymes: Regulatory Regulatory enzymes In a metabolic pathway, which utilizes numerous enzymes, a regulatory enzyme

Enzymes:Regulatory - Reversible covalent modification

Page 6: Enzymes: Regulatorychemistry.creighton.edu/~jksoukup/lec10.pdf · Enzymes: Regulatory Regulatory enzymes In a metabolic pathway, which utilizes numerous enzymes, a regulatory enzyme

Enzymes:Regulatory - Reversible covalent modification

Methylation - involved in chemotaxis in bacteria

ADP-ribosylation -involved in bacterial nitrogen fixation Examples: Diphtheria toxin and cholera toxin D toxin acts on and inhibits EF-2 (protein biosynthesis) C toxin acts on signaling protein (loss of body fluids - death)

Phosphorylation - 1/3 to 1/2 of all euk. proteins are phosphorylated

Page 7: Enzymes: Regulatorychemistry.creighton.edu/~jksoukup/lec10.pdf · Enzymes: Regulatory Regulatory enzymes In a metabolic pathway, which utilizes numerous enzymes, a regulatory enzyme

Enzymes:Regulatory - proteolytic activation

Proproteins/proenzymes - inactive precursor (other proteins)procollagenblood clotting system

Zymogen - inactive precursor (proteases)many proteases activated this way, activationis irreversible