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SLC25A32
The mitochondrial folate transporter (MTF) is a transport protein that facilitates the transfer of tetrahydrofolate across the inner mitochondrial membrane. It is encoded by the SLC25A32 gene and belongs to the mitochondrial carrier superfamily. History The mitochondrial folate transporter was first described in 2000. Role in pathology Mutations of the SLC25A32 gene cause the condition putatively called " riboflavin-responsive exercise intolerance" (RREI), also known as SLC25A32 deficiency. The first case report linking this condition to SLC25A32 was published in 2016. Several additional cases of SLC25A32 deficiency have been described since. The phenotype of the patients is reminiscent of multiple acyl-CoA dehydrogenase deficiency (MADD). According to a review published in 2020, mutations of the SLC25A32 gene have been shown to cause neural tube defect Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from earl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Riboflavin-responsive Exercise Intolerance
Riboflavin-responsive exercise intolerance (SLC25A32 deficiency) is a rare disorder caused by mutations of the SLC25A32 gene that encodes the mitochondrial folate transporter. Patients suffer from exercise intolerance and may have disrupted motor function. A positive correlation between SLC25A32 dysfunction and flavoenzyme deficiency has been observed suggesting that SLC25A32 is in fact a mitochondrial FAD transporter. In mice studies, besides β-oxidation and amino acid metabolism being impaired by mitochondrial FAD deficiency, Slc25a32 wipeout embryos experienced dysfunction of the glycine cleavage system– dihydrolipoamide dehydrogenase. This dihydrolipoamide dehydrogenase dysfunction disrupted folate-mediated one-carbon metabolism, leading a deficiency of 5-methyltetrahydrofolate. Treatment with riboflavin, 5-formyltetrahydrofolate (Folinic acid) and/or L-5-methyltetrahydrofolate (5-MTHF) may lead to a drastic improvement of symptoms. Pyridoxal - 5 - Phosphate (P5P), a cofa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SLC25A32 Deficiency
Riboflavin-responsive exercise intolerance (SLC25A32 deficiency) is a rare disorder caused by mutations of the SLC25A32 gene that encodes the mitochondrial folate transporter. Patients suffer from exercise intolerance and may have disrupted motor function. A positive correlation between SLC25A32 dysfunction and flavoenzyme deficiency has been observed suggesting that SLC25A32 is in fact a mitochondrial FAD transporter. In mice studies, besides β-oxidation and amino acid metabolism being impaired by mitochondrial FAD deficiency, Slc25a32 wipeout embryos experienced dysfunction of the glycine cleavage system– dihydrolipoamide dehydrogenase. This dihydrolipoamide dehydrogenase dysfunction disrupted folate-mediated one-carbon metabolism, leading a deficiency of 5-methyltetrahydrofolate. Treatment with riboflavin, 5-formyltetrahydrofolate (Folinic acid) and/or L-5-methyltetrahydrofolate (5-MTHF) may lead to a drastic improvement of symptoms. Pyridoxal - 5 - Phosphate (P5P), a cofa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mitochondrial Carrier
Mitochondrial carriers are proteins from solute carrier family 25 which transfer molecules across the membranes of the mitochondria. Mitochondrial carriers are also classified in thTransporter Classification Database The Mitochondrial Carrier (MC) Superfamily has been expanded to include both the original Mitochondrial Carrier (MC) familyTC# 2.A.29 and the Mitochondrial Inner/Outer Membrane Fusion (MMF) familyTC# 1.N.6. Phylogeny Members of the MC family (SLC25)TC# 2.A.29 are found exclusively in eukaryotic organelles although they are nuclearly encoded. Most are found in mitochondria, but some are found in peroxisomes of animals, in hydrogenosomes of anaerobic fungi, and in amyloplasts of plants. SLC25 is the largest solute transporter family in humans. 53 members have been identified in human genome, 58 in ''A. thaliana'' and 35 in ''S. cerevisiae''. The functions of approximately 30% of the human SLC25 proteins are unknown, but most of the yeast homologues have been funct ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transport Protein
A transport protein (variously referred to as a transmembrane pump, transporter, escort protein, acid transport protein, cation transport protein, or anion transport protein) is a protein that serves the function of moving other materials within an organism. Transport proteins are vital to the growth and life of all living things. There are several different kinds of transport proteins. Carrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is, they exist within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion (i.e., passive transport) or active transport. These mechanisms of movement are known as carrier-mediated transport. Each carrier protein is designed to recognize only one substance or one group of very similar substances. Researc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tetrahydrofolate
Tetrahydrofolic acid (THFA), or tetrahydrofolate, is a folic acid derivative. Metabolism Human synthesis Tetrahydrofolic acid is produced from dihydrofolic acid by dihydrofolate reductase. This reaction is inhibited by methotrexate. It is converted into 5,10-methylenetetrahydrofolate by serine hydroxymethyltransferase. Bacterial synthesis Many bacteria use dihydropteroate synthetase to produce dihydropteroate, a molecule without function in humans. This makes it a useful target for sulfonamide antibiotics, which compete with the PABA precursor. Functions Tetrahydrofolic acid is a cofactor in many reactions, especially in the synthesis (or anabolism) of amino acids and nucleic acids. In addition, it serves as a carrier molecule for single-carbon moieties, that is, groups containing one carbon atom e.g. methyl, methylene, methenyl, formyl, or formimino. When combined with one such single-carbon moiety as in 10-formyltetrahydrofolate, it acts as a donor of a group ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Inner Mitochondrial Membrane
The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space. Structure The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. The numerous invaginations of the membrane are called cristae, separated by crista junctions from the inner boundary membrane juxtaposed to the outer membrane. Cristae significantly increase the total membrane surface area compared to a smooth inner membrane and thereby the available working space for oxidative phosphorylation. The inner membrane creates two compartments. The region between the inner and outer membrane, called the intermembrane space, is largely continuous with the cytosol, while the more sequestered space inside the inner membrane is called the matrix. Cristae For typical liver mitochondria, the area of the inner membrane is about 5 times as large as the outer membrane due to cristae. This ratio is variable and mitocho ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glutaric Acidemia Type 2
Glutaric acidemia type 2 is an autosomal recessive metabolic disorder that is characterised by defects in the ability of the body to use proteins and fats for energy. Incompletely processed proteins and fats can build up, leading to a dangerous chemical imbalance called acidosis. Genetics Mutations in the '' ETFA'', '' ETFB'', and ''ETFDH'' genes cause glutaric acidemia type II. Mutations in these genes result in a deficiency in one of two enzymes that normally work together in the mitochondria, which are the energy-producing centers of cells. The ETFA and ETFB genes encode two subunits of the enzyme electron transfer flavoprotein, while the ETFDH gene encodes the enzyme electron-transferring-flavoprotein dehydrogenase. When one of these enzymes is defective or missing, the mitochondria cannot function normally, partially broken-down proteins and fats accumulate in the cells and damage them; this damage leads to the signs and symptoms of glutaric acidemia type II. This cond ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Neural Tube Defect
Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embryo begin to change shape and form the neural tube. When the neural tube does not close completely, an NTD develops. Specific types include: spina bifida which affects the spine, anencephaly which results in little to no brain, encephalocele which affects the skull, and iniencephaly which results in severe neck problems. NTDs are one of the most common birth defects, affecting over 300,000 births each year worldwide. For example, spina bifida affects approximately 1,500 births annually in the United States, or about 3.5 in every 10,000 (0.035% of US births), which has decreased from around 5 per 10,000 (0.05% of US births) since folate fortification of grain products was started. The number of deaths in the US each year due to neural tube ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
