Molecular Biology and Biotechnology- ICAR JRF/SRF 2024

• Statement (I) is True: During feedback inhibition (allosteric inhibition), the end-product of a biosynthetic pathway binds to an allosteric regulatory site of an early pathway enzyme already present in the cell, rapidly suppressing its catalytic activity post-translationally.
• Statement (II) is True: During enzyme repression, the accumulating end-product acts as a corepressor, binding to an aporepressor to form an active repressor that silences promoter transcription, thereby shutting down the de novo synthesis of the enzyme at the genetic level.
• Conclusion: Both Statement (I) and Statement (II) are true.

Correct option: (1) Both Statement (I) and Statement (II) are true.

• Statement (A) is Correct: Cyanide ($\text{CN}^-$) binds with ultra-high affinity to ferric iron ($\text{Fe}^{3+}$) in cytochrome $a_3$ of Cytochrome $c$ Oxidase (Complex IV), completely halting electron transfer to oxygen.
• Statement (D) is Correct: Carbon monoxide ($\text{CO}$) binds specifically to ferrous iron ($\text{Fe}^{2+}$) in cytochrome $a_3$ of Complex IV, competing with oxygen and paralyzing respiration.
• Statement (E) is Correct: Chemical uncouplers (e.g., 2,4-dinitrophenol, FCCP) act as lipophilic protonophores, carrying protons across the inner mitochondrial membrane to dissipate the proton-motive force ($\Delta p$), thereby uncoupling ATP synthesis while allowing electron transport to continue.
• Why (B) and (C) are Incorrect: Antimycin A inhibits Complex III at the $Q_i$ site; Piericidin inhibits Complex I (NADH:ubiquinone oxidoreductase), not between cytochromes $b$ and $c$.

• Biotransformation of Mercury: Aquatic anaerobic sediment microorganisms (chiefly sulfate-reducing and iron-reducing bacteria like Desulfovibrio) methylate inorganic divalent mercury ($\text{Hg}^{2+}$) into methylmercury ($\text{CH}_3\text{Hg}^+$).
• Comparative Toxicity: Methylmercury is extremely toxic compared to inorganic mercury because its lipophilicity allows near-complete gastrointestinal absorption, rapid passage across the blood-brain and placental barriers, and intense bioaccumulation/biomagnification through aquatic food webs (responsible for Minamata disease).

Correct option: (2) Extremely toxic over Hg

• Definition of Bioinformatics: Coined by Paulien Hogeweg and Ben Hesper (1970), bioinformatics is the interdisciplinary science that utilizes computational tools, software algorithms, and statistical databases to manage, store, analyze, annotate, and model large-scale macromolecular sequences (DNA, RNA, proteins) and macromolecular 3D structures.
• Distinction from Other Disciplines: Metagenomics is the genomic analysis of uncultured environmental microbial communities; metatranscriptomics analyzes overall community RNA expression; biostatistics encompasses statistical modeling of biological experiments.

Correct option: (3) Bioinformatics