Question

When oxaloacetic acid and acetyl-coenzyme A (acetyl-CoA) labeled with radioactive carbon-14 in position 2 are incubated with citrate synthase, an enzyme of the tricarboxylic acid cycle, only the following enantiomer of \(\left[2-{ }^{14} \mathrm{C}\right]\) citric acid is formed stereoselectively. Note that citric acid containing only \({ }^{19} \mathrm{C}\) is achiral. Assign an \(R\) or \(S\) configuration to this enantiomer of \(\left[2{ }^{14} \mathrm{C}\right]\) citric acid. Note: Carbon- 14 has a higher priority than carbon-12.

Short answer

Answer: The configuration of the [2-14C] citric acid enantiomer is R.

Step-by-step solution

Identify the chiral center

To assign the R or S configuration, we first need to identify the chiral center, which is the carbon atom labeled with radioactive carbon-14 (C-14) in the [2-14C] citric acid.

Determine the priority of the attached groups

According to CIP rules, we need to assign priorities to the groups attached to the chiral center. The higher atomic number gets a higher priority. As given, carbon-14 has a higher priority than carbon-12. So, let's assign the priorities: 1. C-14 (highest priority) 2. COO- (middle priority) 3. CH2COO- (lowest priority) 4. Hydrogen (not shown, least priority)

Orient the molecule and apply CIP rules

We need to orient the molecule in such a way that the least priority group (hydrogen) is on the back (dashed line). After that, we need to determine whether the order of the other three groups follows a clockwise (R) or counterclockwise (S) rotation.

Assign the R or S configuration

After orienting the molecule correctly and following the CIP rules, we can observe that the order of the groups from the highest to the lowest priority (ignoring hydrogen) is in a clockwise direction. Therefore, the configuration of the [2-14C] citric acid enantiomer is R.

Key concepts

Stereochemistry

Stereochemistry is a fascinating branch of chemistry that focuses on the spatial arrangement of atoms within a molecule. It explores how these arrangements can affect the properties and reactions of the molecules. A key aspect of stereochemistry is the study of chiral molecules, which are molecules with non-superimposable mirror images.
This concept is important in biological systems, as many molecules within our bodies, such as amino acids and sugars, are chiral. The tricarboxylic acid cycle, also known as the Krebs cycle, involves several stereospecific reactions where the spatial orientation of molecules plays a crucial role.

• Understanding stereochemistry helps decipher intricate biochemical pathways.
• The spatial arrangement of atoms impacts the reactivity and interaction of molecules.
• Studying stereochemistry is key in developing pharmaceuticals, as different enantiomers can have different biological effects.

Cahn-Ingold-Prelog Priority Rules

The Cahn-Ingold-Prelog (CIP) priority rules are a set of guidelines used to determine the configuration of chiral centers within a molecule. These rules are fundamental in stereochemistry for assigning the R (rectus) or S (sinister) configurations.
Here's how it works:

• Identify the chiral center: Look for the carbon atom that is connected to four different groups.
• Assign priorities: Based on the atomic numbers, assign priorities to the atoms or groups attached; higher atomic numbers receive higher priorities.
• Orient the molecule: Arrange the molecule so that the lowest priority group is pointing away from you.
• Determine configuration: Observe the sequence of the remaining groups. If the sequence is clockwise, the configuration is R. If it's counterclockwise, the configuration is S.

The CIP rules are an invaluable tool for chemists to accurately describe and predict molecular behavior.

Tricarboxylic Acid Cycle

The tricarboxylic acid cycle (TCA cycle), or Krebs cycle, is a vital metabolic pathway that plays a central role in cellular respiration. It takes place in the mitochondria and is responsible for producing energy in the form of ATP.
This cycle involves a series of chemical reactions where acetyl-CoA combines with oxaloacetate to form citrate, which then undergoes transformations to regenerate oxaloacetate, feeding cyclically and producing important coenzymes.
Enzymes like citrate synthase catalyze crucial steps in the cycle, creating intermediates such as citric acid. These intermediates are essential to generate energy and precursor compounds needed for various biosynthetic pathways. Key points include:

• The TCA cycle is fundamental for the conversion of biochemical energy into ATP.
• It provides intermediates necessary for biosynthesis.
• Understanding the TCA cycle helps in studying metabolic disorders and energy regulation in cells.

Enantiomers

Enantiomers are pairs of molecules that are mirror images of each other but cannot be superimposed, much like left and right hands. These structures have identical physical properties, such as melting points and densities, but can react differently in chiral environments.
In the field of chemistry and pharmacology, understanding enantiomers is crucial as they can exhibit vastly different biological activities.

• R and S configurations: Enantiomers are distinguished by their R or S designations according to CIP rules.
• Stereochemistry's impact: The orientation of enantiomers affects their interaction with biological systems, such as enzymes and receptors.
• Biological significance: Many drugs are chiral, and their efficacy and safety can depend on their specific enantiomer.

For example, in the tricarboxylic acid cycle, the formation of [2-14C] citric acid enantiomers and their stereochemistry is significant for studying metabolic pathways and enzyme function.