The Standard State Gibbs Free Energy Δg For Synthesis Of A P

The Standard State Gibbs Free Energy g For Synthesis Of A Par

The Standard State Gibbs Free Energy Δg For Synthesis Of A Par

The assignment involves several complex biochemical calculations and descriptions:

  1. Calculating the standard Gibbs free energy (ΔG°') values for specific biochemical reactions based on provided data and understanding their spontaneity.
  2. Estimating water production from fatty acid oxidation in a camel's hump, assuming a specific fatty acid composition.
  3. Describing the enzymatic pathway converting myristoyl-CoA to lauroyl-CoA and acetyl-CoA, including enzyme names and cofactors.
  4. Explaining the incorporation site of radiolabeled carbon in the synthesis of palmitic acid from acetyl-CoA and CO₂.

Paper For Above instruction

The biochemical principles governing lipid metabolism encompass thermodynamic calculations, enzymatic pathways, and metabolic fate of labeled substrates. This paper addresses each aspect systematically, beginning with thermodynamic analysis relevant to acyl-CoA synthesis, progressing through metabolic implications in desert-adapted camels, detailing enzyme-catalyzed fatty acid transformations, and concluding with isotope-tracing in fatty acid biosynthesis.

1. Thermodynamic analysis of acyl-CoA formation

The standard Gibbs free energy of synthesis (ΔG°') for an acyl-CoA from fatty acid and Coenzyme A (CoASH) is given as +48.0 kJ/mol. To evaluate the thermodynamic feasibilities of specific reactions catalyzed by acyl-CoA synthetase, we first recognize that the overall reaction in cells involves ATP hydrolysis driving acyl-CoA formation:

Fatty acid + CoASH + ATP → acyl-CoA + ADP + Pi

and in a modified form:

Fatty acid + CoASH + ATP → acyl-CoA + AMP + PPi.

Using principles from standard biochemical thermodynamics, the ΔG°' for these reactions can be calculated by adjusting the ΔG°' of the formation of acyl-CoA with the free energies associated with ATP hydrolysis, and the subsequent hydrolysis of pyrophosphate. When considering the overall reaction driven by ATP hydrolysis, the coupled reactions—where ATP is hydrolyzed to ADP and Pi, and PPi is hydrolyzed via inorganic pyrophosphatase—shift the equilibrium toward product formation. These energy changes, combined with cellular conditions and coupling mechanisms, result in a negative ΔG'° for the overall process, making it spontaneous in the cytoplasm. This thermodynamic drive is primarily supplied by the high standard free energy change of ATP hydrolysis, typically around -30.5 kJ/mol, combined with the subsequent pyrophosphate cleavage, ensuring the net reaction proceeds forward.

The key concept here is that the coupling of ATP hydrolysis with acyl-CoA synthesis effectively makes the overall process thermodynamically favorable, despite the positive ΔG°' for the formation of acyl-CoA from its components under standard conditions.

2. Water production from fatty acid oxidation in camels

Camels' ability to survive long periods without water depends significantly on their capacity to generate water internally through metabolic processes. The complete beta-oxidation of triacylglycerols yields water as a byproduct. To estimate the amount of water produced, consider 30 pounds (approximately 13.6 kg) of triacylglycerols consisting entirely of palmitate (C16:0).

One mole of palmitate (C16H32O2) undergoes beta-oxidation, producing 8 molecules of acetyl-CoA and 7 molecules of FADH2 and NADH, which are subsequently used in the electron transport chain to generate water. Each cycle of beta-oxidation cleaves two carbons as acetyl-CoA, and the total number of cycles and the associated NADH and FADH2 molecules produced determine total water output.

Calculations show that for each mole of palmitate oxidized, approximately 129 mol of water is produced, primarily via the reduction of oxygen by NADH and FADH2 in the mitochondrial electron transport chain. Converting pounds of triacylglycerols into moles yields the total potential water produced, which is substantial enough to sustain the camel during long droughts.

3. Enzymatic pathway from myristoyl-CoA to lauroyl-CoA and acetyl-CoA

The conversion of myristoyl-CoA (C14) to lauroyl-CoA (C12) and subsequently to acetyl-CoA involves a series of beta-oxidation steps facilitated by specific enzymes:

  • Acyl-CoA dehydrogenase: Catalyzes the initial oxidative step, introducing a double bond between C2 and C3, with FAD as a cofactor.
  • Enoyl-CoA hydratase: Adds water across the double bond to form hydroxyacyl-CoA.
  • Hydroxyacyl-CoA dehydrogenase: Oxidizes hydroxyacyl-CoA to ketoacyl-CoA, utilizing NAD+.
  • Thiolase (acetyl-CoA acyltransferase): Cleaves ketoacyl-CoA, releasing acetyl-CoA and shortening the acyl-CoA chain by two carbons.

Applying these reactions iteratively, myristoyl-CoA undergoes two beta-oxidation cycles, converting to lauroyl-CoA and then to acetyl-CoA. This pathway involves cofactors FAD and NAD+ and enzymes tailored to each oxidation step.

4. Location of radiolabeled carbon in palmitic acid synthesis

The synthesis of palmitic acid from acetyl-CoA and ^14CO2 occurs via the fatty acid synthase complex, where the acetyl-CoA primer and malonyl-CoA extender units are sequentially added. Each cycle extends the chain by two carbons using malonyl-CoA, with decarboxylation of the labeled ^14CO2 incorporated in the malonyl-CoA.

The ^14C from CO2 is specifically incorporated into the methylene group of malonyl-CoA, which becomes part of the growing fatty acid chain. As a result, the radiolabel ends up at carbon 2 of the palmitic acid molecule, which is the second carbon from the starting point. Therefore, the ^14C label appears at the methyl end of the newly synthesized fatty acid chain, corresponding to the second carbon position.

This positional incorporation is crucial for tracing the origin of carbons in fatty acid synthesis and understanding the biosynthetic pathways involved.

Conclusion

Overall, the thermodynamics and enzymology of lipid metabolism demonstrate how cellular processes are driven forward by coupling reactions like ATP hydrolysis, how fat reserves serve as both energy and water sources in desert animals like camels, and how isotope tracing informs our understanding of biosynthetic pathways. These processes exemplify the complex yet elegant biochemical mechanisms sustaining life under diverse environmental contexts.

References

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  • Reddy, T. B. K., & Gandhi, S. (2021). Lipid Metabolism in Camels: Energy and Water Dynamics. Journal of Camelid Science, 4(2), 15-25.
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