Question

As discussed in Chemical Connections: "Vitamin \(\mathrm{K}\), Blood Clotting, and Basicity" in Section \(26.6 \mathrm{D}\), vitamin \(\mathrm{K}\) participates in carboxylation of glutamic acid residues of the blood-clotting protein prothrombin. (a) Write a structural formula for \(\gamma\)-carboxyglutamic acid. (b) Account for the fact that the presence of \(\gamma\)-carboxyglutamic acid escaped detection for many years; on routine amino acid analyses, only glutamic acid was detected.

Short answer

Answer: γ-carboxyglutamic acid escaped detection in routine amino acid analyses for many years because during the process of protein hydrolysis, γ-carboxyglutamic acid gets decarboxylated back to the common glutamic acid. Since only glutamic acid is detected in the analysis, it made it difficult to identify the presence of γ-carboxyglutamic acid in proteins.

Step-by-step solution

Understanding the role of Vitamin K in carboxylation of glutamic acid residues

Vitamin K participates in carboxylation of glutamic acid residues in the blood-clotting protein prothrombin. The carboxylation of glutamic acid residues generates γ-carboxyglutamic acid which is essential for blood clotting.

Draw a structural formula for γ-carboxyglutamic acid

To find the structural formula of γ-carboxyglutamic acid, first, we need to draw the structure of glutamic acid. The glutamic acid structure contains an amino group (-NH2), a carboxyl group (-COOH), and a side chain with a second carboxyl group (-(CH2)2-COOH). Now, to convert this to γ-carboxyglutamic acid, we need to carboxylate at the γ-position of the side chain. The resulting structure will have an additional -COOH group at the middle carbon atom in the side chain. The structural formula of γ-carboxyglutamic acid is: HOOC-CH(NH2)-CH2-CH2-CH(COOH)-COOH

Discuss the reason why γ-carboxyglutamic acid escaped detection for many years

γ-carboxyglutamic acid escaped detection in routine amino acid analyses for many years because during the process of protein hydrolysis, γ-carboxyglutamic acid gets decarboxylated back to the common glutamic acid. Since only glutamic acid is detected in the analysis, it made it difficult to identify the presence of γ-carboxyglutamic acid in proteins.

Key concepts

Carboxylation

Carboxylation is a crucial biochemical reaction in which a carboxyl group, represented as (-COOH), is added to a molecule. This reaction is essential in the body for modifying certain amino acids, enhancing their function. Vitamin K is a key player in the carboxylation process, particularly for proteins involved in blood clotting, such as prothrombin.

• Vitamin K activates enzymes that facilitate the addition of a carboxyl group.
• The carboxylation of glutamic acid residues in proteins increases their ability to bind calcium ions.
• This calcium binding is vital for the proper functioning of blood-clotting proteins.

Carboxylation essentially transforms inactive proteins into active forms that perform critical physiological roles, ensuring processes like blood clotting occur efficiently.

Glutamic Acid

Glutamic acid is one of the 20 standard amino acids used by cells to build proteins. It plays a fundamental role in metabolism and functions as a crucial neurotransmitter in the brain. Structurally, it contains a carboxyl group, an amino group (-NH2), and a side chain made up of a second carboxyl group.

• It acts as a precursor to γ-carboxyglutamic acid through carboxylation.
• Its structure: HOOC-CH(NH2)-(CH2)2-COOH provides two reactive sites for chemical modifications.
• Glutamic acid is involved in protein synthesis and various cellular activities.

In the context of blood clotting, its modification through carboxylation is fundamental for creating proteins that can interact effectively with calcium ions, aiding in critical bodily functions.

γ-Carboxyglutamic Acid

γ-Carboxyglutamic acid is a modified form of glutamic acid that plays a vital role in blood coagulation. It is formed when a carboxyl group is added to the gamma position of glutamic acid during the carboxylation process.

• This modification enables the protein to bind calcium ions strongly, which is essential for its biological activity.
• The structure: HOOC-CH(NH2)-CH2-CH2-CH(COOH)-COOH shows the additional carboxyl group.
• γ-carboxyglutamic acid is crucial for proteins that regulate blood clotting to function properly.

The inability to detect γ-carboxyglutamic acid accurately in early research stemmed from its conversion back to glutamic acid during protein analysis.

Prothrombin

Prothrombin is a vital protein produced in the liver and is a precursor to thrombin, an enzyme that plays a key role in blood clotting. Vitamin K is essential for the carboxylation of prothrombin, converting it into its active form that can efficiently participate in the coagulation cascade.

• Prothrombin contains multiple glutamic acid residues that require carboxylation to function properly.
• Upon activation, prothrombin is converted into thrombin, which then acts on fibrinogen to form fibrin clots.
• This process helps in wound healing and preventing blood loss.

Without proper carboxylation enabled by Vitamin K, prothrombin would remain inactive, leading to impaired blood clotting and increased bleeding risk.

Blood Clotting

Blood clotting is a complex process essential for stopping bleeding and involves multiple steps and components. The modification of blood clotting proteins, like prothrombin, through carboxylation is critical for the cascade of reactions leading to clot formation.

• Calcium ions play a significant role by bridging between proteins and cell surfaces in the clotting pathway.
• Vitamin K is indispensable in activating proteins responsible for the clotting process.
• Without these modifications, proteins cannot effectively bind calcium, and the clotting process is hindered.

Efficient blood clotting prevents excessive blood loss and is crucial in maintaining hemostatic balance in the body. Each protein and modification step must work correctly to ensure a timely and controlled clotting response.