Regulation of gene expression

Regulation of Gene Expression

Few genetic terms

  • Operon -> A unit of genetic expression consisting of one or more related genes and the operator, repressor and promoter sequences that regulate their transcription.
  • For example -> Lac operon.
  • Inducer -> A  molecule that when bound to a regulatory protein , produces an increase in the expression of a given gene. Lactose is the inducer of Lac operon, IPTG also.

FEW GENETIC TERMS

  • Constitutive gene – The gene that is expressed in a constant rate and not known to be subject of regulation. They are often called house keeping genes.
  • Gratuitous inducer – The inducer that is not a substrate of the enzyme. 
  • For example – Isopropyl Thiogalactosidase (IPTG)

Lac operon

  • Structural genes for 3 enzymes of lactose metabolism in Ecoli (LacZ, LacY, LacA) along with Lac promoter, Lac operator and Lac repressor constitute the Lac operon.
  • This genetic arrangement allows coordinate expression of 3 enzymes of lactose metabolism in bacteria.
  • All the genes are transcribed into a single mRNA

When Ecoli is presented with lactose or IPTG

  • The expression of the activities of β galactosidase, β galactoside permease, and thiogalactoside transacetylase are increased 10 to 100 fold. CAP-cAMP complex required.
  • When there is no lactose or IPTG -> The genes of the above enzymes will not be expressed.

E.coli is exposed to both lactose and glucose

  • The organism first metabolizes glucose, then temporarily stop growing until the genes of Lac operon become induced.
  • When glucose is exhausted then only lactose will induce the genes of lactose metabolism.

Biochemical explanation

  • When no inducer is present -> I gene is a constitutive gene i.e. it is not regulated and is constantly produced.
  • I gene products are the repressor molecules which bind with the operator and prevent binding of RNAP to the promoter and thus prevent subsequent transcription of Lac Z, Lac Y and Lac A.

When lactose or IPTG present

  • The repressor molecules have high affinity for the inducer ( lactose ). So the repressor binds to the inducer and cannot bind to the operator. As a result there is induction of Lac Z, Lac Y and Lac A.
  • For binding of RNAP to the promoter site CAP- cAMP complex is required and the repressor protein must not block the operator locus.

When both lactose and glucose are present

  • Glucose inhibits cAMP so CAP- cAMP will be lacking.  Without CAP – cAMP complex RNAP cannot initiate transcription of Lac Z, Lac Y and Lac A.
  • When glucose is exhausted CAP – cAMP complex will reappear and transcription will start.

Anabolic operon

  • The operon that deals with the anabolic ( synthetic) enzymes is called an anabolic operon.
  • In prokaryotes another operon is there which deals with the enzymes of histidine synthesis. This is called His operon.

Summary

  • Lac operon is a catabolic operon because it deals with the enzymes of lactose catabolism. 
  • Lactose and IPTG are  inducers and +ve regulators.
  • CAP- cAMP complex is +ve regulator.
  • Glucose and repressor molecules are   –ve regulators.
  • Regulation of gene expression in prokaryotes is well explained by Lac operon.
  • Operon is a unit of gene expression that consists of structural genes & regulatory elements.
  • Lac operon is studied in E.coli where lactose is the inducer

Other Biochemistry Notes

. Biochemistry of Proteins

Carbohydrate Metabolism

VITAMIN PYRIDOXINE AND BIOTIN

Vitamin A

Pyrimidine metabolism

Purine Metabolism

Cardiac Biomarkers

VITAMIN D

. Blood Metabolism (Heme synthesis and breakdown)

DNA Repair

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