Question

One of the biological pathways by which an amine is converted to a ketone involves two steps: (1) oxidation of the amine by NAD \(^{+}\) to give an imine and (2) hydrolysis of the imine to give a ketone plus ammonia. Glutamate, for instance, is converted by this process into \(\alpha\) -ketoglutarate. Show the structure of the imine intermediate, and propose mechanisms for both steps.

Short answer

The imine is an intermediate formed during glutamate oxidation, leading to a ketone via imine hydrolysis.

Step-by-step solution

Identify the amine and NAD+ Reaction

Glutamate, which contains an amine group, reacts with NAD+ in an oxidation reaction. This reaction converts the amine group (-NH2) into an imine group (-C=N-) while reducing NAD+ to NADH. To solve this, draw the Glutamate structure where the amine group is replaced by an imine group.

Draw the Structure of the Imine Intermediate

The imine intermediate has the same carbon skeleton as glutamate, but the amine group is oxidized to form an imine. This will look like Glutamate but with the nitrogen double-bonded to its adjacent carbon atom, and the hydrogen removed.

Describe the Hydrolysis of the Imine to a Ketone

In the second step, hydrolysis occurs. The imine group undergoes hydration, followed by breakage of the carbon-nitrogen bond. This process replaces the imine group with a carbonyl group (-C=O) and releases ammonia (NH3). Show the transformation from the imine intermediate to the ketone structure.

Draw the Mechanism of Hydrolysis

Water attacks the carbon of the imine, leading to the addition of a hydroxyl group. The resultant molecule is then tautomerized to break the nitrogen attachment, converting the imine into a ketone and releasing an ammonia molecule.

Key concepts

Biological Oxidation Pathways

Biological oxidation pathways are essential processes in living organisms where organic molecules are converted through oxidation reactions, often with the involvement of coenzymes such as NAD⁺. In the context of amine oxidation, an amine group (-NH₂) is converted to an imine group (-C=N-). This transformation is a crucial step in the metabolism of amino acids. Enzymes called oxidases facilitate this conversion, utilizing NAD⁺ as a cofactor to accept electrons. As the amine group donates electrons and is oxidized to form an imine, NAD⁺ is concurrently reduced to NADH.

These reactions typically occur in cellular environments where control of redox states is vital. They are part of broader metabolic pathways that contribute to key physiological functions, such as energy production and detoxification. The conversion of glutamate to α-ketoglutarate exemplifies this process. Understanding such biological oxidation pathways is crucial for comprehending how cells harness energy from nutrients.

Here are a few key aspects of biological oxidation pathways:

• Involves redox reactions facilitated by enzymes.
• Often utilizes cofactors like NAD⁺.
• Helps in energy production and metabolic regulation.

Imine Hydrolysis Reactions

Imine hydrolysis reactions involve the conversion of imines to carbonyl compounds, such as ketones or aldehydes, through the addition of water. This process is essential in both biological systems and synthetic chemistry. In biological systems, the hydrolysis of imines is crucial for the metabolic conversion of certain nitrogen-containing compounds.

For our specific example, once the amine is oxidized to form an imine, it is further transformed through hydrolysis. Initially, water molecules attack the imine's carbon, introducing a hydroxyl group. This step increases the molecule's stability. Subsequently, the carbon-nitrogen bond breaks, resulting in the formation of a ketone and the release of an ammonia molecule (NH₃).

This transformation is vital as it enables the removal of excess nitrogen from compounds, making the molecules available for further metabolic processes. Imine hydrolysis is a well-known reaction mechanism, often utilized in organic synthesis to create diverse products. Here is a simplification of the steps involved in hydrolysis:

• Water addition to the imine carbon introduces a hydroxyl group.
• Bond cleavage occurs, releasing an ammonia molecule.
• Resulting in the conversion to a carbonyl compound.

Glutamate Conversion Processes

The conversion of glutamate into α-ketoglutarate is a significant metabolic process in the body. This conversion is crucial in the urea cycle and the Krebs cycle, both of which are necessary for energy metabolism and the management of nitrogenous waste.

Glutamate conversion begins with the oxidation of its amine group to an imine, as previously discussed. Following this, the imine intermediate undergoes hydrolysis, yielding α-ketoglutarate and ammonia. α-Ketoglutarate plays a pivotal role in the Krebs cycle as it contributes intermediates for energy production.

In summary, the conversion of glutamate through these reactions aids in:

• Regulating energy supply via the Krebs cycle.
• Facilitating nitrogen metabolism.
• Integrating intermediary metabolic pathways.

Understanding this conversion highlights how amino acid transformations contribute to broader physiological functions, balancing catabolic and anabolic processes within cells.