The MAT2A protein, also known as Methionine Adenosyltransferase II Alpha, is a fundamental component in the human body. It is an enzyme involved in a central metabolic pathway, playing a role in how our cells process and utilize methionine, an amino acid obtained from our diet. Understanding the function of MAT2A helps to illuminate broader aspects of cellular health and disease. This protein influences many bodily functions.
MAT2A’s Primary Role
MAT2A’s core function is enzymatic, catalyzing a reaction that produces S-Adenosylmethionine (SAM or SAMe). This conversion involves combining methionine, an amino acid, with adenosine triphosphate (ATP), the primary energy currency of the cell. This process is the initial step of the methionine cycle, essential for maintaining the balance of methionine within cells.
MAT2A, along with its regulatory subunit MAT2B, is expressed in various non-hepatic tissues and during periods of rapid growth and cell differentiation. The enzyme’s activity is carefully regulated by its product, S-Adenosylmethionine. High levels of SAM can inhibit MAT2A production. This regulatory loop ensures that SAM levels are maintained within a healthy range, preventing excess production.
The Widespread Impact of S-Adenosylmethionine
S-Adenosylmethionine (SAMe), the molecule produced by MAT2A, is a universal methyl donor in biological systems. It provides methyl groups (CH3) for a vast array of biochemical reactions, influencing processes from gene expression to the synthesis of various compounds. SAMe is second only to ATP in its role as a cofactor in numerous biological reactions.
One of SAMe’s significant roles is in methylation, a process where a methyl group is added to a molecule. This includes DNA methylation, which can affect gene activity by turning genes on or off, impacting cellular differentiation and identity. SAMe also contributes to the methylation of proteins, lipids, and RNA, which can alter their function or stability.
Beyond methylation, SAMe is involved in the synthesis of several neurotransmitters, such as dopamine, serotonin, and norepinephrine, crucial for brain function and mood regulation. It also plays a part in cell growth and metabolism, contributing to overall cellular health. Furthermore, SAMe is a precursor for glutathione, a major endogenous antioxidant. This antioxidant capacity is particularly relevant in tissues like the liver and brain.
MAT2A and Its Connection to Disease
Dysregulation or altered activity of the MAT2A protein has been linked to the development and progression of various human diseases. Its involvement often stems from the downstream effects of altered S-Adenosylmethionine (SAMe) levels, which can disrupt numerous cellular processes. Alterations in MAT2A expression are observed in a range of conditions.
In cancer, MAT2A’s role is complex and often associated with changes in cell proliferation, metabolism, and epigenetics. For example, MAT2A is frequently upregulated in several cancers, including liver hepatocellular carcinoma (LIHC), colorectal cancer, glioblastoma, and stomach adenocarcinoma. This increased expression can contribute to tumor growth and survival. Conversely, in some cancers, such as renal cell carcinoma, MAT2A downregulation has been observed, where it may function as a tumor suppressor.
Liver diseases also show a strong connection to MAT2A. In conditions like non-alcoholic fatty liver disease (NAFLD), cirrhosis, and alcoholic liver disease, there can be a switch in methionine adenosyltransferase (MAT) enzyme expression from the liver-specific MAT1A to MAT2A/MAT2B. This shift can lead to reduced SAMe levels in the liver, contributing to the progression of liver damage and even hepatocellular carcinoma. Studies in mouse models where MAT1A is absent have provided insights into how the loss of MAT1A and subsequent increase in MAT2A can lead to liver cancer development.
The protein’s link to SAMe’s role in neurotransmitter synthesis and methylation suggests potential connections to neurological and psychiatric disorders. Imbalances in SAMe metabolism, influenced by MAT2A, may contribute to conditions such as depression and certain neurodegenerative diseases.