#catabolite repression

Microbial Physiology

Catabolite repression ensures that bacteria:

Global carbon regulation termed catabolite repression prioritizes substrate yielding highest growth rate and ATP per investment. In enteric bacteria glucose is fastest because it enters glycolysis directly without conversion steps, PTS transport phosphorylates it preserving energy, yields catabolic enzymes already expressed. Using secondary sugars simultaneously would require synthesis many glycosidases, permeases consuming ribosomes and amino acids reducing fitness. Molecular implementation: glucose transport dephosphorylates PtsG EIIA component which inhibits MalT and LacY permeases via indu

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 10: Catabolite repression and carbon prioritization.

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Microbial Physiology

What happens in catabolite repression?

Glucose represents most energetically efficient carbon source giving maximal ATP per bond and direct entry into glycolysis via phosphotransferase system without induction cost. Bacteria evolved catabolite repression as global control suppressing alternative substrate utilization when glucose present to conserve resources. In Escherichia coli mechanism involves drop in second messenger cAMP due to inhibition of adenylate cyclase CyaA by dephosphorylated EIIA-Glc during glucose transport and prevention of active CRP-cAMP complex formation that binds conserved DNA sequence upstream of lac, araBAD

Ref: Prescott's Microbiology, 11th ed., Chapter 6: Catabolite Repression and Glucose Preference in Bacteria.

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Microbial Physiology

In catabolite repression, bacteria:

Catabolite repression represents global regulatory strategy ensuring efficient use of carbon sources by prioritizing best substrate. In presence of rapidly metabolizable glucose, intracellular cyclic AMP cAMP falls dramatically due to inhibition of adenylate cyclase CyaA by dephosphorylated EIIA-Glc component of phosphotransferase system and increased phosphodiesterase activity. Low cAMP prevents formation of active CRP-cAMP complex that binds conserved motif TGTGA upstream of catabolic operons such as lacZYA for lactose, araBAD for arabinose and malEFG for maltose required for alternative sug

Ref: Prescott's Microbiology, 11th ed., Chapter 6: Catabolite Repression and Efficient Carbon Source Prioritization.

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Microbial Physiology

Diauxic growth occurs when:

Diauxic growth phenomenon first described by Jacques Monod in Escherichia coli grown on mixture of two sugars illustrates hierarchical carbon utilization strategy to maximize energetic efficiency. Cells first consume preferred carbon source glucose offering highest ATP yield per carbon and fastest uptake via phosphotransferase system, generating metabolic signals via dephosphorylated EIIA-Glc that reduce adenylate cyclase activity and cAMP levels plus cAMP-CRP catabolite activator protein thereby diminishing transcription of secondary catabolic operons needed for alternative sugars like lactos

Ref: Madigan et al., Brock Biology of Microorganisms, 16th ed., Chapter 14: Diauxic Growth and Carbon Source Shifts.

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Lac Operon

Catabolite repression is caused by

Catabolite repression establishes hierarchical sugar utilization favoring glucose over lactose for optimal growth efficiency. Elevated glucose transport through phosphotransferase system converts EIIA-Glc to dephosphorylated form that directly inhibits LacY permease activity and reduces adenylate cyclase activation, substantially decreasing intracellular cyclic AMP concentration. Without sufficient cAMP, catabolite activator protein CAP remains as inactive dimer unable to bind its target DNA site centered at -61.5 relative to lac promoter transcription start. RNA polymerase holoenzyme affinity

Ref: NCBI PMC Quantitative approaches to lac bistability – glucose lowers cAMP, CAP fails to bind upstream site, catabolite repression.

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Lac Operon

High glucose concentration leads to

Glucose preference is mediated by phosphotransferase system regulation of cyclic AMP metabolism and inducer exclusion. When extracellular glucose high, EIIA-Glc component remains dephosphorylated, inhibiting adenylate cyclase and activating phosphodiesterase, resulting in sharp drop in intracellular cAMP to low micromolar levels. Low cAMP leaves CAP mainly apo unable to bind upstream site, so even if LacI derepressed by lactose, activation remains poor, producing catabolite repression and diauxic growth. High glucose therefore corresponds to low cAMP and reduced lac transcription despite prese

Ref: Alberts Ch7 Catabolite repression mechanism; NCBI - high glucose leads to low cAMP inactivating CAP CRP

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