Metabolic Control Mechanisms Gene Regulation in Prokaryotes and
Metabolic Control Mechanisms
Gene Regulation in Prokaryotes and Eukarykotes n Prokaryotes n Operons n n n 27% of E. coli genes (Housekeeping genes not in operons) simultaneous transcription and translation n Eukaryotes n n No operons, but they still need to coordinate regulation More kinds of control elements RNA processing Chromatin remodeling n Histones must be modified to loosen DNA
Control of enzyme production at the level of transcription Constitutive enzymes – enzymes are synthesized even in the absence of substrates n Inducible enzymes – synthesized only in the presence of substrates or other substances n Expression of genes is regulated by induction or repression n
Operon n A unit of genetic material that functions in a coordinated manner by means of an operator, a promoter, and one or more structural genes that are transcribed together.
Induction n System is always “OFF” unless an inducer is present
Repression n System is always “ON” unless a corepressor suppresses gene expression
Lac operon Inducible operons are normally off When lactose is present, repressor can no longer bind DNA. Transcription occurs
Active repressor binds to operator Trp Operon DNA No RNA made m. RNA Protein Tryptophan (corepressor) Active repressor Trp Tryptophan present -> repressor active -> operon “off”.
Control of enzyme activity Zymogen activation n Allosteric regulation n Regulation by covalent modification n Non –covalent modification or protein interaction n
Zymogens - Activation of chymotrypsinogen
Allosteric enzymes n n Allosteric: Greek allo + steric, other shape Allosteric enzyme: an oligomer whose biological activity is affected by other substances binding to it n n Allosteric effector: a substance that modifies the behavior of an allosteric enzyme; may be an n these substances change the enzyme’s activity by altering the conformation(s) of its tert or 4° structure allosteric inhibitor allosteric activator Aspartate transcarbamoylase (ATCase) n feedback inhibition
Phosphorylation Presence of phosphate can convert an inactive precursor or vice versa n Phosphorylating agent - ATP n Amino acid residues that can be phosphorylated : serine, threonine and tyrosine n
Enzyme regulation by polymerization n Acetyl. Co. A carboxylase
Compartmentalization
Compartmentalized pathways n n n n Mitochondrion – TCA, fatty acid degradation Cytosol – glycolysis and fatty acid synthesis Urea cycle- part mitochondrion part cytosol Gluconeogenesis – part cytosol part mitochondrion Nucleus – nucleic acid synthesis Lysosome – digestion Peroxisomes - oxidations
‘Energy Charge’ Adenylates provide phosphoryl groups to drive thermodynamically unfavorable reactions n Energy charge is an index of how fully charged adenylates are with phosphoric anhydrides n If [ATP] is high, E. C. 1. 0 n If [ATP] is low, E. C. 0 n
Regulation by energy charge
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