The protein Multidrug and Toxin Extrusion Protein 1, commonly called MATE1, is a transporter embedded in the membranes of certain cells. It functions like a cellular gatekeeper, allowing traffic to move only out of the cell.
As a member of the solute carrier (SLC) family, MATE1 recognizes and binds to various molecules inside the cell. The protein then uses energy to actively push the substance outside. This process prevents the buildup of potentially toxic compounds, playing a protective role for the cell.
The Primary Function of MATE1
The primary role of the MATE1 transporter is to perform efflux, the process of actively pumping substances out of cells. It functions as a proton antiporter, meaning it exchanges its target molecules, which are mostly organic cations, for protons. This exchange is driven by a proton gradient and allows the cell to clear a diverse range of compounds that could otherwise cause harm.
MATE1 handles several categories of substances. It is involved in removing endogenous waste products from the body’s metabolic processes, such as creatinine. The transporter also clears environmental toxins and a wide array of drug compounds, facilitating their ultimate elimination from the body.
This transporter often collaborates with other transporter proteins, forming a functional unit with organic cation transporters (OCTs) in many tissues. These transporters are responsible for bringing organic cations from the bloodstream into the cells. MATE1 then completes the process by expelling them from the other side of the cell, ensuring a continuous and directional flow of substances out of the body.
Key Locations in the Body
The MATE1 protein is strategically positioned in organs central to waste removal and detoxification. Its highest concentrations are in the liver and kidneys, where it is situated on specific cellular surfaces to maximize its excretory function.
In the kidneys, MATE1 is located on the apical membrane of the proximal tubule cells. This surface faces the inside of the tubule where urine is formed. MATE1 pushes waste products and drug metabolites from inside these cells directly into the forming urine, ensuring they are flushed out of the body.
Within the liver, MATE1 resides on the canalicular membrane of hepatocytes, which are the main liver cells. This membrane forms the tiny canals that collect bile. Here, the transporter moves substances from the liver cells into the bile, which is then transported to the intestine for eventual elimination.
Impact on Medications
The function of the MATE1 transporter has significant implications in pharmacology due to its role in clearing drugs. Many medications are substrates for MATE1 and are actively removed by it. This directly influences their concentration in the bloodstream and their overall duration of action.
A prominent example involves metformin, a widely prescribed medication for type 2 diabetes. The renal clearance of metformin is heavily dependent on MATE1 activity in the kidneys. The transporter pumps metformin from the kidney’s tubule cells into the urine, which is a primary route of its excretion, affecting both its effectiveness and potential for side effects.
This transporter is also a focal point for drug-drug interactions. Some drugs can act as inhibitors of MATE1, blocking its function. If an inhibitor is taken with a drug cleared by MATE1, it can prevent the second drug’s removal. This can lead to an accumulation of the second drug, potentially reaching toxic levels and increasing the risk of adverse reactions like with the acid reducer cimetidine.
Genetic Differences and Health
The gene responsible for producing the MATE1 protein is SLC47A1. Variations in its DNA sequence, known as genetic polymorphisms, can exist among individuals. These changes can lead to the production of MATE1 transporters that function differently from one person to the next.
These genetic differences can alter the efficiency of the MATE1 transporter. Some polymorphisms may result in a more active protein, clearing substances from cells at a faster rate. Other variations might lead to a less active transporter, causing slower removal of its target substrates and contributing to diverse drug responses.
An individual’s genetic makeup regarding the MATE1 gene can influence their response to certain medications. A person with a less active version of MATE1 may clear a drug like metformin more slowly, increasing its concentration and the risk of side effects. Conversely, someone with a hyper-functional variant might eliminate the drug so quickly that it doesn’t reach an effective concentration. This link is a growing area of interest in personalized medicine.