Enzyme Regulation and Gene Expression

Gene Functions: Proteins and Enzymes

• Gene regulation is crucial for various biological processes, including development and metabolic activities
• Different genes exert their functions at specific times and amounts
• Gene regulation mechanisms include turning genes on and off, and regulating the level of production
• Examples such as Tay-Sachs disease, X-linked muscular dystrophy, and Huntington's disease demonstrate the importance of gene expression timing
  • Tay-Sachs: expressed in the first few years of life
  • X-linked muscular dystrophy: damages teenagers
  • Huntington's disease: starts in middle adult life

Regulation of Gene Action

• Genetic information transfer is outlined by the Central Dogma of Molecular Biology.
• Regulation of gene action is also necessary
• Constitutive enzymes are constantly and consistently synthesized
  • Examples include glycolytic pathway enzymes
• Inducible enzymes are present in small amounts, but increase in concentration when their substrate is present, especially if the substrate is the cell's sole energy source.

Coordinate Induction and Repression

• Coordinate induction is the induction of related enzymes or proteins by a single inducing agent
  • Coordinate induction involves a group of proteins working together
• Coordinate repression is the repression of enzymes that catalyze consecutive biosynthetic reactions
  • Coordinate repression is triggered by the end product of the series of biosynthetic reactions it catalyzes
  • This is frequently referred to as end-product repression

Definitions of Gene Action Terms

• Structural gene: carries the message for the amino acid sequence, which a specific protein is made of
• Regulatory gene: codes for the repressor
  • It dictates whether structural gene transcription happens or not.
• Operator or o locus: site in the DNA to which the repressor molecule attaches
  • Prevents structural gene transcription if a repressor is bound
• Promoter or p: specific DNA sequence that RNA polymerase finds to initiate transcription
• Repressor: protein coded for by the regulatory gene
• Co-repressor: small molecule that binds the aporepressor to activate it from an inactive state

Negative Transcriptional Control

• The negative transcriptional system is characterized by the production of a repressor protein by the regulatory gene
  • This system can either be inducible or repressible

The Lactose (Lac) Operon

• Lac operon is a set of genes in E. coli responsible for lactose uptake and metabolism.
• It includes a single promoter and is transcribed as a single mRNA molecule.
• Genes in the lac operon produce proteins that enable bacteria to use lactose as an energy source

Operon Model

• The operon model describes a cluster of functionally related structural genes and their adjacent transcriptional control regions
• The operon model describes how genes work together
• The lac operon contains genes that produce the enzymes necessary to break down lactose

The Lac Operon and Lactose

• Lactose being present leads to inactivation of repressor, so RNA polymerase can transcribe genes coding necessary enzymes to break down lactose
• If lactose levels are high, enzymes associated with the breakdown of lactose will be produced
• In absence of lactose, repressor protein is activated and binds to operator, blocking RNA polymerase.

Lactose Mutations

• Structural-gene mutations prevent either ẞ-galactosidase or permease production
  • Mutations in lacz or lacy genes affect protein sequence
• Operator mutations prevent repressor attachment, leading to continuous gene expression
  • Mutations in operator region prevent repression, resulting in constitutive expression
• Mutations in the promoter region disrupt the ability of RNA polymerase to bind, resulting in a lack of gene expression

The Tryptophan (trp) Operon

• Tryptophan operon consists of five consecutive genes necessary to produce enzymes that make tryptophan
  • Bacteria will use tryptophan from environment, or they make their own using enzymes from this operon
• When tryptophan is present, repressor is active
  • Preventing transcription of the operon, resulting in less production of tryptophan producing enzymes
• When tryptophan is absent, the repressor is inactive
  • Allowing transcription of the operon so tryptophan-producing enzymes can be produced

Positive Transcriptional Control System

• Positive control involves the regulator gene product stimulating transcription
  • This is in contrast to negative control which represses gene expression
• The role of the active repressor protein is to enable or enhance recognition of the promoter by RNA polymerase, or to enable polymerase to proceed past the attenuator
• The arabinose operon is an exemplary system for positive transcriptional control

The Arabinose Operon

• The arabinose operon produces enzymes that catalyze the conversion of L-arabinose to D-xylulose
• The arabinose operon regulates gene expression similarly to the lac operon
  • Gene expression is regulated in the absence of glucose
  • The structural genes and enzyme products are illustrated in Figure 6-17

Regulation of Gene Action in Eukaryotes: The Davidson-Britten Model

• The Davidson-Britten Model suggests a complex regulatory mechanism involving multiple interacting genes in eukaryotes
  • It describes four types of genes: sensor, integrator, receptor, and structural genes
  • These genes interact through multiple receptor sites
• This ensures the accurate expression of structural genes in response to diverse cellular signals

Control of Specific Gene Expression by Hormones

• Hormones are crucial regulators for gene expression, influencing various cellular functions like growth, metabolism, and stress responses
• The Stein, Spelsberg, and Kleinsmith model explains steroid hormone binding and their impacts on gene regulation
• The model has multiple steps
  • Steroid hormone binding to intracellular receptor
  • Hormone-receptor complex formation
  • Translocation to the nucleus
  • Binding to DNA
  • Transcription activation
  • mRNA production and Protein synthesis