Isotopic tracing in lipid biosynthesis: If bacterial cells synthesizing fatty acids are fed radioactive bicarbonate (HCO3−), where would you expect the bulk of the radioactivity to be found after synthesis?

Difficulty: Medium

Correct Answer: cellular bicarbonate

Explanation:


Introduction / Context:
Radioisotopic tracers help map carbon flow through metabolic pathways. In fatty acid biosynthesis, bicarbonate (as CO2) participates in a key carboxylation step, but whether its carbon remains in the final lipid depends on the detailed chemistry of the elongation cycle.



Given Data / Assumptions:

  • Bacteria are actively synthesizing fatty acids de novo.
  • Radioactive bicarbonate (e.g., 14C-HCO3−) is supplied.
  • Standard malonyl-CoA pathway via acetyl-CoA carboxylase is operative.


Concept / Approach:

Acetyl-CoA carboxylase catalyzes the biotin-dependent carboxylation of acetyl-CoA to form malonyl-CoA, using bicarbonate as the source of the carboxyl carbon. In the subsequent Claisen condensation during chain elongation, the carboxyl group of malonyl (derived from bicarbonate) is released as CO2. Therefore, although bicarbonate is essential for the chemistry, its carbon does not become part of the long-chain fatty acid; it is lost each cycle as CO2.



Step-by-Step Solution:

HCO3− + acetyl-CoA → malonyl-CoA (carboxylation).Malonyl-ACP condenses with the growing acyl chain; decarboxylation releases CO2.The isotope from HCO3− is largely lost as CO2 rather than incorporated into the fatty acid chain.Thus, radioactivity remains in cellular inorganic carbon pools (bicarbonate/CO2), not in the lipids or membranes.


Verification / Alternative check:

Classic labeling experiments show poor incorporation of 14C from bicarbonate into fatty acid carbon skeletons compared with labeled acetate or acetyl units; the decarboxylation step accounts for isotope loss.



Why Other Options Are Wrong:

“the fatty acids” or “the cytoplasmic membrane”: the labeled carbon is not retained in the acyl chain carbons; membrane lipids thus show little incorporation from bicarbonate.

“nucleic acids”: bicarbonate is not a primary carbon donor for nucleic acid synthesis; labeled incorporation would be minimal relative to cellular inorganic pools.



Common Pitfalls:

Assuming all carbon sources fed to cells end up in macromolecules; overlooking decarboxylation steps that release the label.



Final Answer:

cellular bicarbonate

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