User:Stellur/sandbox

Information needed:

- Lacks sufficient corresponding inline citations

- Requires more references

- Sources do not provide page references

- Information on different types of uniporters

- Mechanism of uniporters

- Include more discoveries

- More information on the role of uniporters

Information that will be added into the article:

- Add more information into the lead section in regards to the physiological roles uniporters play in biological body

- Fix incorrect information of the function of uniporters

- Add information and subsection on the type of uniporters

- The sentence "Calcium released from the presynaptic neuron binds to a ligand-gated calcium channel in the postsynaptic neuron to stimulate an impulse in that neuron." needs to be removed as it is incorrect

- Update content on the mechanism of uniporters - they are not the same ion channels as written in the original article

Lead (adding to original article)
"Uniporters are found in mitochondria and neurons.The uniporter in the mitochondria is responsible for calcium uptake.  The calcium channels are used for cell signaling and triggering apoptosis. The calcium uniporter transports calcium across the inner mitochondrial membrane and is activated when calcium rises above a certain concentration."

"Voltage-gated potassium channels are also uniporters that can be found in neurons and are essential for action potentials."

Discovery

 * Fick's Laws of Diffusion (1855) laid the groundwork
 * Overton's work in the 1890s highlighted the concept of semipermeability in biological membranes, crucial for understanding substance regulation in cells.
 * Wittenberg and Scholander's discovery of facilitated diffusion suggested membrane proteins' role in molecular transport.
 * Studies in the 1960s-1970s focused on nutrient transport specificity, showcasing the selectivity of membrane transport proteins.

Glucose transporter

 * GLUTs: Transporters moving glucose across cells for energy.
 * 12-helix structure; SLC2 genes; 3 classes with varied roles.
 * GLUT1 in brain, red cells; GLUT2 in liver, insulin release.
 * GLUT3 in brain, high affinity; GLUT4 regulated by insulin.
 * GLUT5 for fructose; transport without ATP for energy processes.

Mitochondrial Ca2+ Uniporter (MCU)

 * Mitochondrial Calcium Uniporter (MCU): Located in inner mitochondrial matrix, regulates calcium uptake from cytoplasm.
 * Function: Manages energy production, cytosolic calcium signaling, and cell death regulation.
 * Activation: MCU triggered by cytoplasmic calcium levels above 1 uM.
 * Components: MCU complex consists of pore-forming, regulatory (MICU1, MICU2), and auxiliary (EMRE) subunits.

Large neutral amino acid transporter (LAT1)

 * LAT1: Transports neutral amino acids.
 * Prefers specific amino acid types.
 * Crucial for intestinal, placental, and brain barrier transport.
 * Part of SLC7 transporter family, forms 4F2hc complex.
 * Controversy: Uniporter or antiporter, linked to cancer metabolism.

Equilibrative Nucleoside transporters (ENTs)

 * ENTs: Transport nucleosides, nucleobases, and drugs.
 * Functions: Essential for nucleic acid synthesis, energy metabolism.
 * Direction: Moves nucleosides down concentration gradient, aids drug delivery.
 * MFS: ENTs work via clamp-and-switch model.
 * Human ENTs: hENT1-3 and hENT4 with varying tissue distribution.
 * Tissue Distribution: hENT1 in multiple organs, hENT2 in neurological tissues, hENT3 in cerebral cortex, hENT4 as PMAT for organic cations.

Mechanism

 * Uniporters: Transport molecules/ions passively down concentration gradients.
 * Mechanism: Bind specific substrates, induce protein conformational changes.
 * Conformational Changes: Capture substrate, translocate across membrane, release substrate.
 * Unidirectional: Transport one molecule/ion based on concentration gradient.
 * Dependency: Relies on substrate concentration difference for transport, no ATP required.

Physiological Processes
Physiological Roles:


 * Nutrient Uptake: e.g., GLUTs for glucose uptake in energy production.
 * Ion Homeostasis: Maintain balance of Na+, K+, Ca2+, Cl- ions in cells.
 * Metabolism: Transport ions, amino acids, molecules for metabolic pathways and energy.
 * Cell Signaling: Calcium uniporters regulate intercellular calcium levels for signal transduction.
 * Waste Removal: Aid in removing metabolic waste products and toxins.
 * pH Regulation: Help maintain acid-base balance within cells through ion transport.

Mutations in Uniporters

 * SLC2A1 Gene Mutations (GLUTs):
 * Cause GLUT1 Deficiency Syndrome: Impaired glucose transport to the brain.
 * CFTR Gene Mutations (ion channels):
 * Lead to Cystic Fibrosis: Thick mucus affects breathing, digestion.
 * KCNA1 Gene Mutations (potassium channels):
 * Cause Hypokalemic Periodic Paralysis
 * SLC6A19 Gene Mutations (amino acid transporter):
 * Result in Hartnup Disease: Impaired amino acid absorption in intestines, kidneys.
 * AGXT Gene Mutations (peroxisomal membrane transporter):
 * Lead to Primary Hyperoxaluria: Oxalate accumulation causes kidney stones, damage.