The sulfhydryl group of coenzyme A plays an important role in the biosynthesis of fatty acids from units of acetic acid. The key steps are suggested to be carboxylation with carbon dioxide of acetyl coenzyme \(\mathrm{A}\) (which is a thioester abbreviated as O=CSC(=O)O to give malonyl coenzyme \(\mathrm{A}\) followed by condensation of the malonyl coenzyme A with acetyl coenzyme \(\mathrm{A}\), or a molecule of an acyl coenzyme \(\mathrm{A}\), to produce an acyl malonyl coenzyme \(\mathrm{A}\) This is followed by decarboxylation and reduction to an acyl coenzyme \(A\) with two more carbon atoms than the starting acyl coenzyme \(\mathrm{A}\). Each repetition of the process gives a fatty acid (or thioester of a fatty acid) with an additional two carbons. All the steps are of course controlled by specific enzymes. \(5^{\prime}-\) (adenosine 3' -phosphate) \(-\mathrm{OP}(\mathrm{O})(\mathrm{OH}) \mathrm{OP}(\mathrm{O})(\mathrm{OH}) \mathrm{OCH}_{2} \mathrm{C}\left(\mathrm{CH}_{3}\right)_{2}\) \(\mathrm{CH}(\mathrm{OH})-\mathrm{CONH}\left(\mathrm{CH}_{2}\right)_{2} \mathrm{CONH}\left(\mathrm{CH}_{2}\right)_{2} \mathrm{SH}\) coenzyme \(\mathrm{A}(\mathrm{CoA}\) SH ) (a) Write out the complete structure of coenzyme A as corresponds to the above condensed formula; what products would you expect coenzyme \(\mathrm{A}\) to give on vigorous hydrolysis? (b) Work out the steps for synthesis of hexanoic acid from acetic acid with the acid of coenzyme \(A\), using the abbreviation CoA-SH and indicating the general nature of each step in terms of the kind of reagents that might be used to achieve it in ordinary laboratory operations. What advantages would you expect to accrue from CoA-SH as compared to CoA-OH as the acyl carrier? (c) Suppose the enzymic synthesis of hexanoic acid to be carried on in the presence of radioactive carbon dioxide; would the postulated course of the reaction be precluded if the hexanoic acid produced were completely devoid of radioactivity? Explain in detail.

Step by step solution

01

Write out the structure of coenzyme A

Based on the condensed formula given, the complete structure of coenzyme A (CoA) is as follows: \[5'-\text{Adenosine}-3'-\text{phosphate}-\text{OP( O)( OH) OP(O)( OH) OCH}_{2}\text{C(CH}_{3}\text{)CH( OH)-}\text{CONH(CH}_{2}\text{)CONH(CH}_{2}\text{)SH}\]

02

Predict products of CoA on vigorous hydrolysis

Upon vigorous hydrolysis, coenzyme A (CoA) would break down into its constituent components: adenosine, phosphate groups, and the sulfhydryl group. The products formed would be adenosine, orthophosphate, 2-pyrophosphate, and the sulfhydryl containing compound.

03

Identify steps in the synthesis of hexanoic acid from acetic acid

To synthesize hexanoic acid from acetic acid with the help of coenzyme A, we can follow these general steps: 1. Formation of Acetyl-CoA: Acetic acid reacts with CoA-SH to form Acetyl-CoA (Acetyl thioester of coenzyme A). 2. Carboxylation: Acetyl-CoA reacts with carbon dioxide (CO2) to form Malonyl-CoA, where an extra carbon is added to the acetyl group. 3. Condensation: Malonyl CoA reacts with another Acetyl-CoA (or a molecule of acyl-CoA) to form an acyl-malonyl CoA. 4. Decarboxylation: Acyl-malonyl CoA undergoes decarboxylation, removing the extra carbon added earlier and forming an acyl-CoA with two more carbon atoms than the starting acyl-CoA. 5. Reduction: Acyl-CoA is reduced to form a fatty acid with an additional two carbon atoms. Each repetition of steps 2-5 will convert the starting acetyl-CoA to a longer-chain fatty acid with two additional carbon atoms.

04

Compare CoA-SH and CoA-OH as acyl carriers

CoA-SH acts as a good acyl carrier due to the presence of the reactive sulfhydryl (-SH) group, which makes the formation of acyl-CoA thioester derivatives more facile. Using CoA-OH would involve ester linkages, which are less reactive and less energy-rich than thioester linkages. Thus, CoA-SH is a better acyl carrier than CoA-OH because it provides more reactive and energy-rich intermediates, facilitating the biosynthesis process.

05

Analyze radioactivity in hexanoic acid synthesis

If the enzymatic synthesis of hexanoic acid is carried out in the presence of radioactive carbon dioxide, it is expected that the radioactive carbon would be incorporated into malonyl-CoA since this molecule is formed by carboxylation of acetyl-CoA with carbon dioxide. However, if the final hexanoic acid product is completely devoid of radioactivity, it suggests that the radioactive carbon was released during the decarboxylation step. This implies that the radioactive carbon is not a part of the final hexanoic acid product and does not preclude the postulated course of the reaction.

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