Glucose transporter (GLUTs) The glucose transporter (GLUTs) is a type of uniporter responsible for the
facilitated diffusion of glucose molecules across cell membranes.
Glucose is a vital energy source for most living cells, however, due to its large size, it cannot freely move through the cell membrane. The glucose transporter is specialized in transporting glucose specifically across the membrane. The GLUT proteins have several types of
isoforms, each distributed in different
tissues and exhibiting different
kinetic properties. Humans have been found to express fourteen GLUT proteins. Class I GLUTs include
GLUT1, one of the most studied isoforms, and
GLUT2. When glucose binds to the glucose transporter, the protein channels change shape and undergo a conformational change to transport the glucose across the membrane. Once the glucose unbinds, the protein returns to its original shape. The glucose transporter is essential for carrying out physiological processes that require high energy demands in the brain, muscles, and kidneys by providing an adequate amount of energy substrate for
metabolism.
Diabetes, an example of a condition that involves glucose metabolism, highlights the importance of the regulation of glucose uptake in disease management.
Mitochondrial uniporter (MCU) The
mitochondrial calcium uniporter (MCU) is a protein complex located in the inner mitochondrial matrix that functions to take up calcium ions (Ca2+) into the
matrix from the
cytoplasm. The transport of calcium ions is specifically used in cellular function for regulating energy production in the mitochondria, cytosolic
calcium signaling, and
cell death. The uniporter becomes activated when cytoplasmic levels of calcium rise above 1 uM. These subunits work together to regulate the uptake of calcium in the mitochondria. Specifically, the EMRE subunit functions for the transport of calcium, and the MICU subunit functions in tightly regulating the activity of MCU to prevent the overload of calcium concentrations in the cytoplasm.
LAT1 favors the transport of amino acids with large branched or
aromatic side chains. The amino acid transporter functions to move essential amino acids into the
intestinal epithelium,
placenta, and
blood-brain barrier for cellular processes such as metabolism and cell signaling. The transporter is of particular significance in the
central nervous system as it provides the necessary amino acids for protein synthesis and
neurotransmitter production in brain cells. Over-expression of LAT1 has been found in human
cancer and is associated with playing a role in cancer metabolism.
Equilibrative nucleoside transporters (ENTs) The
nucleoside transporters, or
equilibrative nucleoside transporters, are uniporters that transport
nucleosides,
nucleobases, and
therapeutic drugs across the cell membrane. Nucleosides serve as building blocks for
nucleic acid synthesis and are key components for energy metabolism in creating
ATP/
GTP. They also act as ligands for
purinergic receptors such as
adenosine and
inosine. ENTs allow the transport of nucleosides down their concentration gradient. They also have the ability to deliver nucleoside analogs to intracellular targets for the treatment of
tumors and viral infections. ENTs are part of the
Major Facilitator Superfamily (MFS) and are suggested to transport nucleosides using a clamp-and-switch model. In this model, the substrate first binds to the transporter, which leads to a conformational change that forms an occluded state (clamp). Then, the transporter switches to face the other side of the membrane and releases the bound substrate (switching). ENTs have been found in
protozoa and mammals. In humans, they have been discovered as ENT3 (hENT1-3) and
ENT4 (hENT4) transporters. ENTs are expressed across all tissue types, but certain ENT proteins have been found to be more abundant in specific tissues. hENT1 is found mostly in the
adrenal glands,
ovary,
stomach and
small intestines. hENT2 is expressed mostly in neurological tissues and small parts of the
skin, placenta,
urinary bladder,
heart muscle and
gallbladder. hENT3 is expressed highly in the
cerebral cortex,
lateral ventricle,
ovary and
adrenal gland. hENT4 is more commonly known as the
plasma membrane monoamine transporter (PMAT), as it facilitates the movement of organic
cations and biogenic
amines across the membrane. == Mechanism ==