Question

Mevalonic acid is the precursor of the terpenes. Write its structure. After phosphorylation, it undergoes a decarboxylative elimination to yield 3 -isopentenyl pyrophosphate. Outline the mechanism of this reaction. Where does the driving force for the reaction come from?

Short answer

Mevalonic acid has the structure \( CH_3-CH_2-C(CH_3)_2-CH_2-CH_2-COOH \). Upon phosphorylation, it converts to mevalonic acid phosphate, forming a reactive intermediate with two phosphate groups. Decarboxylation occurs, releasing CO₂ and forming a double bond between C2 and C3, yielding 3-isopentenyl pyrophosphate. The reaction's driving force comes from the high-energy phosphate bonds in ATP and the release of CO₂ during decarboxylation.

Step-by-step solution

Draw the structure of mevalonic acid

Mevalonic acid is a 6-carbon compound with 2 methyl groups at the 3-carbon position, a carboxylic acid group at one end, and a primary alcohol group at the other end. Its structure is as follows: \[ CH_3-CH_2-C(CH_3)_2-CH_2-CH_2-COOH \] Now that we have the structure of mevalonic acid, let's move on to the mechanism of its conversion to 3-isopentenyl pyrophosphate.

Outline the phosphorylation of mevalonic acid

The first step in the reaction is the phosphorylation of mevalonic acid-hydroxyl group. This occurs when a molecule of ATP transfers its terminal phosphate group to the oxygen atom of the hydroxyl group in mevalonic acid, forming a phosphate ester bond and converting ATP to ADP. The resulting intermediate is known as mevalonic acid phosphate.

Outline the decarboxylative elimination

In the next stage of the reaction, mevalonic acid phosphate undergoes decarboxylative elimination. A second molecule of ATP transfers a phosphate group to the oxygen atom of the carboxylic acid group in mevalonic acid phosphate, forming another phosphate ester bond and converting ATP to ADP. This creates a highly reactive intermediate with two phosphate groups. The decarboxylation reaction now occurs, with the molecule losing carbon dioxide (CO₂), and the phosphate group from the carboxylic acid end moving to the primary alcohol end. This generates a double bond between C2 and C3, finally yielding 3-isopentenyl pyrophosphate and CO₂ as products.

Identify the driving force of the reaction

The formation of the double bond between C2 and C3 is highly favorable, as it ultimately forms the isoprenoid unit, which is the basis for all terpenes. But the driving force for the reaction comes from the high-energy phosphate bonds present in the ATP molecules. The release of energy during the conversion of ATP to ADP and the subsequent attachment of the phosphate groups to mevalonic acid ensures that the reaction is thermodynamically favorable and proceeds in the direction of 3-isopentenyl pyrophosphate formation. Additionally, the release of carbon dioxide during decarboxylation also helps push the reaction forward.

Key concepts

Phosphorylation Mechanism

Phosphorylation is a key step in the conversion of mevalonic acid to 3-isopentenyl pyrophosphate. In this process, a phosphate group from a molecule of ATP is transferred to the hydroxyl group present on the mevalonic acid molecule. This forms a phosphate ester bond. The attachment of the phosphate group is vital as it primes the mevalonic acid for further reaction stages.
Phosphorylation not only modifies the chemical structure of the molecule but also increases its reactivity, creating mevalonic acid phosphate. The introduction of the phosphate group adds a level of energy through the high-energy phosphate bond, ultimately leading the way for subsequent reaction steps. This mechanism of phosphorylation ensures the compound is adequately prepared to undergo additional transformations in the pathway toward becoming 3-isopentenyl pyrophosphate.

Decarboxylative Elimination

Following phosphorylation, decarboxylative elimination is the next crucial step where mevalonic acid phosphate undergoes significant structural changes. Here, another molecule of ATP transfers a phosphate group to the carboxyl end of the molecule. This double phosphorylation step results in an intermediate that has become more reactive due to the presence of multiple phosphate groups.
Decarboxylation involves the removal of carbon dioxide (CO₂) from the carboxylic acid group, driven by the energy contributed by the high-energy phosphate groups. Simultaneously, a phosphate group migrates from the carboxylic end to the primary alcohol end. This process generates a double bond between the C2 and C3 carbons, culminating in the formation of a new structure: 3-isopentenyl pyrophosphate.

ATP to ADP Conversion

The conversion of ATP (adenosine triphosphate) to ADP (adenosine diphosphate) is central to the energy dynamics of the reaction pathway. ATP acts as an energy donor through its terminal phosphate groups. During both phosphorylation steps, ATP releases one of its phosphate groups, converting to ADP and releasing a significant amount of energy. This energy is crucial for assisting the reaction's progression.

• In the first step, ATP donates a phosphate group to the hydroxyl group of mevalonic acid, creating mevalonic acid phosphate.
• In the second step, another ATP molecule undergoes a similar conversion to facilitate the decarboxylative elimination.

The energy released during ATP's conversion to ADP supports the overall reaction by making both phosphorylations and the subsequent reactions exergonic and favorable.

Isopentenyl Pyrophosphate Formation

The final product of the reaction, 3-isopentenyl pyrophosphate, is a crucial building block for the biosynthesis of isoprenoids, which include terpenes. This compound is formed through a series of well-orchestrated biochemical transformations that include both phosphorylation and decarboxylative elimination mechanisms.
During the reaction pathway, following successful phosphorylation and decarboxylation steps, isopentenyl pyrophosphate emerges as the product. Its structure consists of an isoprenoid unit characterized by a five-carbon skeleton with a distinct double bond between C2 and C3. This particular arrangement of carbon atoms and phosphate groups makes isopentenyl pyrophosphate a highly reactive and versatile precursor for synthesizing a wide range of biomolecules in living organisms.