29. GENETIC CODE AND INHIBITION OF PROTEIN SYNTHESIS

Genetic Code:

The genetic code is the set of instructions stored in messenger RNA (mRNA) that guides the synthesis of proteins in the body. It tells the ribosomes which amino acids to add and in what order. These instructions are written in the form of codons — groups of three nucleotide bases (A, G, C, and U) that represent specific amino acids.

Characteristics of the Genetic Code:

  • Number of codons: There are 64 possible codons (4³ combinations using A, G, C, and U). Each codon represents one amino acid or a signal to stop protein synthesis.
  • Stop codons (termination codons): Three codons — UAA, UAG, and UGA — do not code for any amino acid. They signal the end of the polypeptide chain. These are also known as nonsense codons and are sometimes called amber, ochre, and opal codons.
  • Degenerate but unambiguous code: Because 61 codons code for only 20 amino acids, most amino acids are represented by more than one codon — this is called degeneracy. However, each codon always codes for the same specific amino acid, making the code unambiguous. Degeneracy helps reduce the harmful effects of mutations.
  • Synonymous codons: Codons that code for the same amino acid are called synonyms. For instance, arginine has six codons, while methionine (AUG) and tryptophan (UGG) each have only one.
  • Almost universal code: The genetic code is nearly the same across all organisms, with minor exceptions such as in human mitochondria:
    • UGA codes for tryptophan instead of acting as a stop codon.
    • AUA codes for methionine instead of isoleucine.
    • CUA codes for threonine instead of leucine.
  • Non-overlapping and continuous: Codons are read one after another without overlapping or punctuation. For example, the sequence AUGCUAGACUUU is read as AUG / CUA / GAC / UUU.

Wobble Hypothesis for Codon–Anticodon Interaction:

The genetic code assumes that codons in mRNA pair with anticodons in tRNA in an antiparallel manner. However, researchers found that some tRNAs can recognize more than one codon. This flexibility in pairing is known as the Wobble Hypothesis, proposed by Francis Crick.

For example, in yeast tRNA for alanine, the anticodon IGC (which contains inosine) can bind to three codons — GCU, GCC, and GCA. The first two bases pair normally, but the third base “wobbles”, allowing flexibility. This explains how a limited number of tRNAs can read multiple codons.

Crick’s Four Rules of the Wobble Hypothesis:

  1. The first two bases of the codon follow standard Watson-Crick base pairing.
  2. Codons that differ in the first or second base must be recognized by different tRNAs. For example, UUA and CUA both code for leucine but require separate tRNAs.
  3. The first base of the anticodon determines its reading capacity:
    • If the first base is C or A → it reads only one codon.
    • If the first base is U or G → it can read two codons.
    • If the first base is inosine (I) → it can read three codons.
  4. It is not necessary to have 61 tRNAs for 61 codons. A minimum of 32 tRNAs can read all codons efficiently.

Inhibition of Protein Synthesis:

Protein synthesis can be blocked by certain antibiotics and toxins, many of which target specific steps in translation. Most antibiotics affect prokaryotic ribosomes, while eukaryotic ribosomes remain unaffected, which is why these drugs are useful in treating bacterial infections.

Common Inhibitors of Protein Synthesis:

  1. Puromycin: Derived from mold, its structure resembles the 3′ end of aminoacyl-tRNA. It gets incorporated into the growing peptide chain, causing premature termination of protein synthesis.
  2. Tetracyclines: These antibiotics block the binding of aminoacyl-tRNA to the A-site on the ribosome, preventing elongation of the peptide chain.
  3. Chloramphenicol: It inhibits the enzyme peptidyl transferase on the 50S ribosomal subunit, stopping peptide bond formation.
  4. Erythromycin: Binds to the 50S ribosomal subunit and blocks the translocation step, preventing the ribosome from moving along mRNA.
  5. Streptomycin: Binds to the 30S ribosomal subunit, causing misreading of the genetic code and interfering with the binding of initiating tRNA.
  6. Tunicamycin: Inhibits the attachment of oligosaccharide side chains to glycoproteins, disrupting proper protein folding.
  7. Cycloheximide: Inhibits protein synthesis in eukaryotes by blocking peptidyl transferase activity of the 60S ribosomal subunit.
  8. Diphtheria toxin: Produced by Corynebacterium diphtheriae, this toxin inactivates elongation factors in eukaryotes, halting protein synthesis and causing severe cellular damage.

Detailed Notes:

For PDF style full-color notes, open the complete study material below:

Share your love