Overview of transmembrane transporters
Without the aid of proteins, very few molecules can enter or leave cells, or cross organellar membranes. Even water and urea, which can diffuse across pure phospholipid bilayers, are still accelerated by transporting proteins frequently. There are three major classes of transmembrane transporters, which are all integral transmembrane proteins and show a high degree of specificity for transporting substances. These three types of transport speeds depend to a large extent on the differences in operational mechanisms.
Three types of transmembrane transporters
ATP-powered pumps which are ATPases, use the energy from ATP hydrolysis to move ions or small molecules across the membrane to resist chemical concentration gradients or potentials. This process is also regarded as active transport. In this case, transport of ions or small molecules is coupled to the hydrolysis of ATP to ADP and Pi which will release energy. The overall process (“uphill” movement of ions or small molecules and the ATP hydrolysis) is energetically favorable. The low calcium (Ca2+) and sodium (Na+) ion concentration is maintained by such pumps in virtually all animal cells. So it keeps the pH inside animal-cell lysosomes, plant-cell vacuoles, and the lumen of the stomach.
Channel proteins are involved in an energetically favorable reaction, which transport water or some specific types of ions down their concentration or electric potential gradients. Multiple water molecules or ions move simultaneously through a protein-lined passageway which is formed by the channel proteins. They can reach a very rapid rate ------ up to 108 per second. The potassium-specific channel proteins in the plasma membrane of all animal cells are generally open and are very crucial to generate the normal, resting electric potential across the plasma membrane. Many other types of channel proteins are usually closed and only open in respond to some specific signals. These types of ion channels play fundamental roles in nerve cells.
Transporters also move a wide variety of ions and molecules across cell membranes. But unlike channel proteins, transporters only bind one or a few molecules at a time. After the binding, the transporters will undergo a conformational change, so that it can bind substrate molecules, and only these molecules will be transported across the membrane. Therefore, because of the conformational change, transporters transport only 102-104 molecules per second, which is lower than that related with channel proteins.
The membrane transporters are essential for the normal cell function. If there is something wrong with transmembrane transporters, there will be a lot of bad outcomes. Following are some examples. Amino acid transporters (AATs), membrane-bound transport proteins, mediate the transfer of amino acids into and out of cells or cellular organelles. AATs have many kinds of functional roles ranging from neurotransmission to acid-base balance, anabolic and catabolic reactions, and intracellular energy metabolism. In cancer cells and diabetes, dysregulation of AATs results in metabolic reprogramming, which changes the level of intracellular amino acids, contributing to cancer, obesity and diabetes. Indeed, the neutral amino acid transporters (NATs) SLC7A5/LAT1 and SLC1A5/ASCT2 are likely involved in several human malignancies. On the other side, the results of transporters on central nervous system (CNS) drug development are getting more and more important because of their influences on clinical trials. Membrane transporters give us insight into the mechanisms of treatment failure, adverse drug reactions, and individual differences in the treatment of neurological and psychiatric disorders. The uptake and efflux transporters in capillary endothelial cells mediate drug transport from bloodstream to the organs. For example, these membrane transporters have an essential effect in the digestive tract, the kidney, the liver, as well as other organic systems such as the blood cells, the placenta, and the CNS. All cells selectively transport endogenous and exogenous compounds across the membrane to maintain an intracellular milieu distinct from the outer one. This function is achieved partly by the membrane transporters, which are multi-specific transport proteins. Therefore, these transporters will display physiologic functions according to the endogenous compounds they transport, whether hormones, amino acids, bile acids, or lipids.