Cell Information: Cells contain the complete information necessary to synthesize any protein relevant to their function at any required time and location.
Protein Synthesis Control: The synthesis of proteins must be regulated to ensure the appropriate protein is produced in suitable quantities at the right times.
Purpose of Regulation:
Ensures certain enzymes are synthesized only in the presence of their substrates.
Prevents the synthesis of enzymes when their products are present in excess.
Energy and Material Conservation: Regulation conserves energy and raw materials (e.g., amino acids).
Control Points: Gene expression can be regulated at various stages of protein synthesis:
In prokaryotic cells, the most efficient regulatory control occurs during transcription.
In eukaryotic cells, regulation is more complex and involves various transcription factors which can up- or down-regulate the transcription of target genes.
RNA Processing: The RNA produced from transcription is initially an unprocessed transcript; further processing leads to maturation of mRNA, which is then translated. This translation also has differential regulation.
Post-transcriptional Modifications: The final polypeptide product undergoes various modifications, e.g., targeting and degradation.
Feedback Inhibition: Both eukaryotic and prokaryotic gene expressions can be regulated through feedback inhibition.
Up-regulation: An increase in gene expression or protein synthesis due to internal or external signals.
Down-regulation: A decrease in gene expression or protein synthesis.
5.2 Objectives
By the end of this section, students should be able to:
Explain the basis of regulation of gene expression.
Explain end-product inhibition.
Describe the structure and explain the function of the Lac Operon system.
5.3 Inducible and Repressible Systems
Inducible System: Usually in the ‘switched off’ state until an inducer molecule is present, which activates gene expression.
Repressible System: Typically in the ‘switched on’ state but can be suppressed by a co-repressor molecule.
5.4 The Lac Operon
Overview: The lac operon comprises three structural genes regulated by a regulator gene, working alongside a promoter, an operator, and a terminator sequence.
Structural Genes:
lacZ gene: Encodes enzyme β-galactosidase that hydrolyzes lactose into glucose and galactose.
lacY gene: Encodes β-galactoside permease, a protein that facilitates lactose transport into the cell.
lacA gene: Encodes β-galactoside transacetylase, which modifies lactose.
Function in E. coli: The lac operon is crucial for lactose metabolism in Escherichia coli and related bacteria. When glucose is absent, the cell relies on lactose as an energy source, necessitating the production of enzymes to metabolize lactose (β-galactoside).
Energy Management: The lac operon ensures that energy is expended on enzyme production only when necessary, utilizing a repressor molecule to halt enzyme synthesis in the absence of lactose.
Repressor Mechanism:
The repressor has two active sites, where:
An inducer (lactose) can attach to ‘switch on’ the operator gene.
A co-repressor (glucose) can bind to ‘switch off’ the operator gene.
Transcription Process:
When the operator is switched on, transcription occurs, and mRNA is synthesized, leading to polypeptide formation.
When switched off, no mRNA is produced, thus halting polypeptide synthesis.
Figures:
Figure 5.1 illustrates lactose breakdown into glucose and galactose.
Figure 5.2: Depicts the lac operon in the repressed state, showing the repressor protein binding to the operator and preventing transcription.
Figure 5.3: Shows the lac operon in the induced state; when lactose is present, it alters the repressor's shape, allowing transcription to occur.
5.4.1 The Lac Operon in the Repressed State
In this state, the repressor protein binds to the operator site, preventing transcription of the genes z, y, and a, thus switching them off.
5.4.2 The Lac Operon in the Induced State
In the presence of lactose, it alters the repressor’s shape, preventing it from binding to the operator, thereby allowing for transcription of genes z, y, and a.
5.4.3 End-Product Inhibition
When E. coli is grown in glucose medium, the regulator gene produces a repressor that binds the co-repressor (glucose), activating it, which then binds to the operator gene, effectively switching off the entire lac operon.
This process exemplifies end-product inhibition, also termed negative feedback control, by preventing the synthesis of enzymes necessary for glucose production from lactose, as glucose is already available.
5.5 Revision Questions
Are all prokaryotic genes expressed all the time? Discuss.
How do prokaryotic cells switch off mRNA synthesis when enzymes are not needed?
Explain the non-simple, complex gene control employed by eukaryotes.
Define inducible enzymes and the conditions under which cells produce these enzymes.
Discuss whether cancer-causing genes are inducible or repressible.
Define an operon and describe the structure of the lac operon.
Explain the function of each part of the lac operon.
Define structural genes.
Elaborate on the process of end-product inhibition using a named end-product.
Discuss why glucose is regarded as a co-repressor in the lac operon function.
Differentiate between the induced state and the repressed state of the lac operon.
5.6 Summary
Regulation of Gene Expression: Refers to the mechanisms through which cells can activate or deactivate transcription and translation processes. It enables organisms to express proteins only when needed, thus minimizing waste of materials and energy.
Lac Operon: A classical example of gene regulation discovered by Jacob and Monod, it illustrates how E. coli expresses enzymes for lactose metabolism strictly in the presence of lactose and absence of glucose.
Operon Definition: A cluster of genes regulated by a single promoter, allowing coordinated expression of functionally related proteins.
Eukaryotic Complexity: Gene expression in eukaryotes is more intricate than in prokaryotes, regulated at multiple levels, including:
Transcription of DNA into RNA.
Post-transcriptional modification of primary RNA transcripts.
Translation of mRNA into polypeptides.
Post-translational modification of polypeptide chains.
Cell differentiation.
Growth and development.
Each of these steps provides a point of control for gene expression in eukaryotes.