AMT - Aminomethyltransferase mitochondrial | Elisa - Clia - Antibody - Protein

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Background:

AMT or Aminomethyltransferase also known as Glycine N-Methyltransferase (GNMT), plays a role in the metabolism of amino acids, particularly glycine (Glycine cleavage system,GCS). AMT/GNMT is an enzyme found in the mitochondria of cells, particularly in the liver. Its primary function is to catalyze the conversion of glycine to sarcosine (N-methylglycine) in the presence of S-adenosylmethionine (SAM). This reaction is part of the methionine cycle, which is involved in the metabolism of methionine, an essential amino acid. The methionine cycle is important for various metabolic processes, including the synthesis of proteins, DNA, and other molecules. In the methionine cycle, methionine is converted to SAM, which is a universal methyl donor in numerous biological reactions. AMT/GNMT helps regulate the levels of SAM by converting glycine to sarcosine, thereby indirectly affecting methionine metabolism. SAM, produced in the methionine cycle, is a key methyl donor for various methylation reactions which are essential for the regulation of gene expression, metabolism of neurotransmitters, and other critical processes

Protein Structure:

• Aminomethyltransferase Domain: AMT contains a specific domain that catalyzes the transfer of the aminomethyl group from glycine to tetrahydrofolate, producing 5,10-methylenetetrahydrofolate and ammonia.
• Mitochondrial Targeting Sequence: AMT has a mitochondrial targeting sequence that directs the protein to the mitochondria, where it becomes active.
• Active Site: The active site contains conserved residues essential for its enzymatic function, including binding sites for its substrates and cofactors.

Classification and Subtypes:

• Family: AMT belongs to the glycine cleavage system family, which includes four proteins: glycine decarboxylase (P-protein), aminomethyltransferase (T-protein), dihydrolipoamide dehydrogenase (L-protein), and glycine cleavage system protein H (H-protein).
• Isoforms: There is one main isoform of AMT, primarily located in the mitochondria.

Function and Biological Significance:

• Glycine Degradation: AMT is crucial for the glycine cleavage system, where it facilitates the conversion of glycine into carbon dioxide, ammonia, and 5,10-methylenetetrahydrofolate. This process is vital for amino acid catabolism and the regulation of glycine levels in the body.
• Energy Metabolism: By participating in the degradation of glycine, AMT indirectly influences cellular energy metabolism and mitochondrial function.
• One-Carbon Metabolism: The product 5,10-methylenetetrahydrofolate is an important intermediate in one-carbon metabolism, necessary for DNA synthesis and repair.

Interactions:

• Glycine Cleavage System Components: AMT interacts with other components of the GCS, including P-protein, L-protein, and H-protein, to facilitate the sequential degradation of glycine.
• Tetrahydrofolate: AMT binds tetrahydrofolate as a cofactor, essential for the transfer of the aminomethyl group.

Clinical Issues:

• Nonketotic Hyperglycinemia (NKH): Mutations in the AMT gene can lead to NKH, a rare inherited disorder characterized by elevated levels of glycine in the blood and cerebrospinal fluid. Symptoms include severe neurological deficits, developmental delay, and seizures.
• Metabolic Disorders: Dysregulation of AMT activity can disrupt glycine and one-carbon metabolism, potentially leading to broader metabolic imbalances.

Summary:

Aminomethyltransferase (AMT) is a mitochondrial enzyme that plays an essential role in the glycine cleavage system, contributing to amino acid degradation and energy metabolism. It catalyzes the transfer of an aminomethyl group from glycine to tetrahydrofolate, producing important metabolic intermediates. Mutations in AMT can cause nonketotic hyperglycinemia (NKH), a severe metabolic disorder. Understanding the function and regulation of AMT is crucial for elucidating its role in metabolic pathways and associated diseases.