Metabolism of amino acids of pyruvate and oxaloacetate group, involvement of these amino acids in metabolic processes.

Amino acids are converted to 7 common metabolic intermediates: oxaloacetate, alpha-ketoglutarate, pyruvate, succinyl coA, Acetoacetyl CoA, Acetyl CoA, and fumarate. The pyruvate and oxaloactetate groups are glucogenic intermediates. Amino acids of the pyruvate and oxaloacetate group are those that can be converted into pyruvate or oxaloacetate during metabolism. These amino acids play crucial roles in energy production, gluconeogenesis, and other metabolic pathways.

The Amino Acids that we classify in the group of pyruvate include: threonine , glycine , serine , alanine , cysteine. Those that we classify into the oxaloacetate group include aspartate and asparagine.

Pyruvate Group

• The pyruvate group includes alanine, glycine, serine, cysteine, and threonine.

Alanine

• The process of transamination, which is fully reversible, requires an amino acid and an alpha-keto acid to produce a different amino acid and alpha-keto acid. Simply, an amino group is transferred from one amino acid to the alpha-keto acid. This reaction allows the body to synthesize non-essential amino acids.
• Alanine is converted to pyruvate be the removal of an amino group by ALT (alanine aminotransferase ). In this reaction, the amino group is reversibly transferred from alanine to 2-alphaketoglutarate to form pyruvate and glutamate.

Transamination to form Pyruvate from Alanine.

Serine

• Serine is converted to pyruvate in a reaction catalyzed by serine dehydratase and H2O and NH4 + are released .

Glycine

• Glycine is converted into serine by the enzyme serine hydroxymethyltransferase where glycine donates a one carbon unit to THF (tetrahydrofolate). Serine then undergoes deamination, loses an amino group, and loses a water molecule to form pyruvate.

Conversion of Glycine to Pyruvate

Threonine

• Threonine can be degraded into pyruvate through a minor metabolic pathway involving multiple enzymatic steps. This pathway is less common than its conversion to succinyl-CoA but still contributes to energy metabolism.
• Threonine is first converted to 2-Amino-3-Ketobutyrate by Threonine dehydrogenase (TDH). NAD⁺ is reduced to NADH in this step. Then, 2-Amino-3-Ketobutyrate is cleaved to Glycine & Acetyl-CoA by 2-Amino-3-ketobutyrate CoA ligase. As mentioned above, glycine can be converted to pyruvate in a two step process, Glycine to serine, and serine to pyruvate. Acetyl-CoA enters the Krebs cycle for energy production.

Metabolic Fate of Pyruvate

Pyruvate can be converted to to glucose in gluconeogenesis as well as enter the Krebs cycle by being converted to acetyl CoA for energy production. It can also be reduced to lactate under anaerobic conditions in lactic acid fermentation.

Oxaloacetate group

• The oxaloacetate group includes aspartate and asparagine.
• asparagine itself can be converted to aspartate then oxaloacetate, or aspartate can directly be converted to oxaloacetate.

Enzyme: Aspariginase

Asparagine and Aspartate

Aspartate is converted to oxaloacetate by a transaminase, a reversible reaction. Its amino group can be removed and added to alpha-ketoglutarate which generates oxaloacetate from aspartate and gluatamate. Pyridoxal phosphate (PLP) is a cofactor.

Asparagine on the other hand is hydrolyzed by aspariginase, which releases aspartate and ammonia. Aspartate can then be converted to oxaloacetate by AST.

Reaction catalyzed by aspartate aminotransferase: Aspartate + α-ketoglutarate ⇌ oxaloacetate + glutamate

Metabolic fate of Oxaloacetate

Oxaloacetate combines with acetyl-CoA to form citrate, continuing the Krebs cycle for energy production. Oxaloacetate also serves as a precursor for aspartate, which is used to synthesize other amino acids, nucleotides, and urea cycle intermediates.

Resources

Literature

• Abali. Lippincott Illustrated Reviews: Biochemistry. Wolters Kluwer, 2021.
• Lieberman, Michael, and Alisa Peet. Marks’ Essentials of Medical Biochemistry: A Clinical Approach. Wolters Kluwer, 2015.