SLC11A2
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SLC11A2
Natural resistance-associated macrophage protein 2 (NRAMP 2), also known as divalent metal transporter 1 (DMT1) and divalent cation transporter 1 (DCT1), is a protein that in humans is encoded by the ''SLC11A2'' (solute carrier family 11, member 2) gene. DMT1 represents a large family of orthologous metal ion transporter proteins that are highly conserved from bacteria to humans. As its name suggests, DMT1 binds a variety of divalent metals including cadmium (Cd2+), copper (Cu2+), and zinc (Zn2+,); however, it is best known for its role in transporting ferrous iron (Fe2+). DMT1 expression is regulated by body iron stores to maintain iron homeostasis. DMT1 is also important in the absorption and transport of manganese (Mn2+). In the digestive tract, it is located on the apical membrane of enterocytes, where it carries out H+-coupled transport of divalent metal cations from the intestinal lumen into the cell. Function Iron is not only essential for the human body, it is required f ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Transferrin
Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encoded by the ''TF'' gene and produced as a 76 kDa glycoprotein. Transferrin glycoproteins bind iron tightly, but reversibly. Although iron bound to transferrin is less than 0.1% (4 mg) of total body iron, it forms the most vital iron pool with the highest rate of turnover (25 mg/24 h). Transferrin has a molecular weight of around 80 kDa and contains two specific high-affinity Fe(III) binding sites. The affinity of transferrin for Fe(III) is extremely high (association constant is 1020 M−1 at pH 7.4) but decreases progressively with decreasing pH below neutrality. Transferrins are not limited to only binding to iron but also to different metal ions. These glycoproteins are located in various bodily fluids of vertebrates. Some inv ...
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Single-nucleotide Polymorphism
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently large fraction of the population (e.g. 1% or more), many publications do not apply such a frequency threshold. For example, at a specific base position in the human genome, the G nucleotide may appear in most individuals, but in a minority of individuals, the position is occupied by an A. This means that there is a SNP at this specific position, and the two possible nucleotide variations – G or A – are said to be the alleles for this specific position. SNPs pinpoint differences in our susceptibility to a wide range of diseases, for example age-related macular degeneration (a common SNP in the CFH gene is associated with increased risk of the disease) or nonalcoholic fatty liver disease (a SNP in the PNPLA3 gene is associated with inc ...
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Restless Legs Syndrome
Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This is often described as aching, tingling, or crawling in nature. Occasionally, arms may also be affected. The feelings generally happen when at rest and therefore can make it hard to sleep. Due to the disturbance in sleep, people with RLS may have daytime sleepiness, low energy, irritability and a depressed mood. Additionally, many have limb twitching during sleep. RLS is not the same as habitual foot tapping or leg rocking. Risk factors for RLS include low iron levels, kidney failure, Parkinson's disease, diabetes mellitus, rheumatoid arthritis, pregnancy and celiac disease. A number of medications may also trigger the disorder including antidepressants, antipsychotics, antihistamines, and calcium channel blockers. There are two main ty ...
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MPTP
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a prodrug to the neurotoxin MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. It has been used to study disease models in various animal studies. While MPTP itself has no psychoactive effects, the compound may be accidentally produced during the manufacture of MPPP, a synthetic opioid drug with effects similar to those of morphine and pethidine (meperidine). The Parkinson-inducing effects of MPTP were first discovered following accidental injection as a result of contaminated MPPP. Toxicity Injection of MPTP causes rapid onset of Parkinsonism, hence users of MPPP contaminated with MPTP will develop these symptoms. MPTP itself is not toxic, and as a lipophilic compound can cross the blood–brain barrier. Once inside the brain, MPTP is metabolized into the toxic cation 1-methyl-4-phenylpyridinium (MPP+) by the enzyme monoamine oxidase B (M ...
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Substantia Nigra
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the substantia nigra appears as a continuous band in brain sections, anatomical studies have found that it actually consists of two parts with very different connections and functions: the pars compacta (SNpc) and the pars reticulata (SNpr). The pars compacta serves mainly as a projection to the basal ganglia circuit, supplying the striatum with dopamine. The pars reticulata conveys signals from the basal ganglia to numerous other brain structures. Structure The substantia nigra, along with four other nuclei, is part ...
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Blood Brain Barrier
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the Cell (biology), cells, and transports Metabolic waste, metabolic waste products away from those same cells. Blood in the circulatory system is also known as ''peripheral blood'', and the blood cells it carries, ''peripheral blood cells''. Blood is composed of blood cells suspended in blood plasma. Plasma, which constitutes 55% of blood fluid, is mostly water (92% by volume), and contains proteins, glucose, mineral ions, hormones, carbon dioxide (plasma being the main medium for excretory product transportation), and blood cells themselves. Albumin is the main protein in plasma, and it functions to regulate the colloidal osmotic pressure of blood. The blood cells are mainly red blood cells (also called RBCs or erythrocytes), white blood cells (also called WBCs or leukocytes) and platelets (also called thrombocytes). The most abund ...
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Multiple Sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, blindness in one eye, muscle weakness, and trouble with sensation or coordination. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). In the relapsing forms of MS, between attacks, symptoms may disappear completely, although some permanent neurological problems often remain, especially as the disease advances. While the cause is unclear, the underlying mechanism is thought to be either destruction by the immune system ...
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Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most common type of motor neuron diseases. Early symptoms of ALS include stiff muscles, muscle twitches, and gradual increasing weakness and muscle wasting. ''Limb-onset ALS'' begins with weakness in the arms or legs, while ''bulbar-onset ALS'' begins with difficulty speaking or swallowing. Half of the people with ALS develop at least mild difficulties with thinking and behavior, and about 15% develop frontotemporal dementia. Most people experience pain. The affected muscles are responsible for chewing food, speaking, and walking. Motor neuron loss continues until the ability to eat, speak, move, and finally the ability to breathe is lost. ALS eventually causes paralysis and early death, usually from respiratory failure. Most cases of ALS (a ...
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Parkinson's Disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms become more common. The most obvious early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking. Cognitive and behavioral problems may also occur with depression, anxiety, and apathy occurring in many people with PD. Parkinson's disease dementia becomes common in the advanced stages of the disease. Those with Parkinson's can also have problems with their sleep and sensory systems. The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to a dopamine deficit. The cause of this cell death is poorly understood, but involves the build-up of misfolded proteins into Lewy bodies in the neurons. Collectively, the main motor symptoms are also known as ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term memory, remembering recent events. As the disease advances, symptoms can include primary progressive aphasia, problems with language, Orientation (mental), disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and challenging behaviour, behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an alle ...
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Fet3p
Fet3p is a multicopper oxidase (MCO)2 found in ''Saccharomyces cerevisiae'' with a structure consisting of three cupredoxin-like β-barrel domains and four copper ions located in three distinct metal sites (T1 in domain 3, T2, and the binuclear T3 at the interface between domains 1 and 3). Fet3p is a type I membrane protein with an orientation that places the amino-terminal oxidase domain in the exocellular space (Nexo) and the carboxyl terminus in the cytoplasm (Ccyt). Part of the ferroxidase reaction, Fet3p catalyzes the oxidation of Fe(II) to Fe(III) using O2 as substrate. The Fe(III) generated by Fet3p is a ligand for the iron permease The permeases are membrane transport proteins, a class of multipass transmembrane proteins that allow the diffusion of a specific molecule in or out of the cell in the direction of a concentration gradient, a form of facilitated diffusion. The per ..., Ftr1p. References {{Portal bar, Biology, border=no Oxidoreductases ...
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