Compartmentation
Active: Regulation of Rate Limiting Enzyme
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Substrate availability and Compartmentation? Passive mechanism
? Limited capacity
? Anabolic and Catabolic pathways separated
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E.g. Fatty acid synthesis & Fatty acid oxidation? Specialized subcellular compartments (Hydrolases in Lysosomes)
Controlling Rate Limiting Enzyme
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Regulation of? Regulation of Enzyme
Enzyme quantity
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synthesis
Regulation of
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? Al osteric RegulationEnzyme catalytic
activity
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? Covalent Modification
Regulation of enzyme synthesis
? Gene Transcription induction and Repression
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? HMG-CoA reductase by cholesterol? PEP carboxykinase by insulin and glucagon
? Cytochrome P450 by various drugs
? Slow Process
? Long Term Effect
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Regulation of enzyme catalytic activity
Allosteric Regulation
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? Within seconds? Allosteric Enzymes: Catalysis at active site modulated
by presence of effector at allosteric site
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? Positive or negative effectors? May affect affinity (K series) or
? Catalytic activity (V series)
Homotropic or Heterotropic effectors
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? Homotropic:? Heterotropic
? Substrate itself an effector
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? Effector different from
? Mostly, Positive effector
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substrate? Exhibit cooperativity
? Feedback inhibition
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? Hyperbolic curve
? Hills equation define
characteristics
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Examples of allosteric regulation
? Most of the rate limiting steps in metabolic pathways
? Feedback inhibitions
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? Phosphofructokinase? Aspartate transcarbamoylase
? Which of the following describes a characteristic of
most allosteric enzymes?
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? (A) They are composed of single subunits.
? (B) They show cooperativity in substrate binding.
? (C) They have allosteric activators that bind in the catalytic site.
? (D) They have irreversible allosteric inhibitors that bind at allosteric
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sites.
Covalent modification
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Partial ProteolysisPhosphorylation
Partial proteolysis
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? Proteases synthesized as inactive precursor:Proproteins/Proenzymes/Zymogens
? Eg. Pepsin, Tr ypsin, Chymotrypsin, Clotting factors
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? Irreversible modification
? Selective Proteolysis leads to conformation change and
configures active site
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Phosphorylation/Dephosphorylation
? Catalysed by Protein kinases and Phosphoprotein phosphatases
? Act on serine, threonine and tyrosine residues
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? May increase or decrease activityExample
? High Insulin/Glucagon Ratio decreases c AMP and Protein kinase
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A causing dephosphorylation of PFK-2 (Active)? Active PFK2 increases Fructose 2,6-bisphosphate that increases
PFK-1 activity causing increased glycolysis
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? Reverse happens under the effect of glucagon that increases
phosphorylation by in increasing c AMP
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Phosphorylation/Dephosphorylation? Most common mechanism employed for regulation
? Ease of interconversion
? Chemical nature of phosphoryl group helps in conformational changes of
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enzymes
? H bond formation by O
? Negative charge
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? Insulin/ Glucagon hormones regulates enzymes
Summary
Enzyme
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Regulation
Active:
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Passive:Regulation
substrate
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of Enzyme
availability/Co
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activitympartmentatio
n
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Enzyme
Allosteric
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CovalentSynthesis
Regulation
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Modification
References
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? Victor W. Rodwell, David A. Bender, Kathleen M. Botham, Peter J. Kennelly,P. Anthony Weil. Harper's Illustrated Biochemistry, 30th Edition
? Denise R. Ferrier; Lippincott Illustrated Reviews Biochemistr y, 7th Edition
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