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PDF Download British Pharmacopoeia: 2014 EditionFrom Brand: Stationery Office These proteins enable electron transport from the cytosol into the mitochondria, as the inner mitochondrial membrane is impermeable for the electron carrier NADH. Additionally, two mitochondrial transporters are known: the malate-2-oxoglutarate/malate carrier, OGC ( SLC25A11) and the two isoforms of the aspartate-glutamate carrier, AGC1 (also known as aralar SLC25A12) mainly expressed in the brain and AGC2 (also known as citrin SLC25A13) in the liver. The mitochondrial malate aspartate shuttle (MAS) ( Figure 1) consists of six proteins, of which four are enzymes: cytosolic NAD(H)-dependent malate dehydrogenase (encoded by MDH1), aspartate aminotransferase/glutamic oxaloacetic transaminase ( GOT1) and their mitochondrial counterparts ( MDH2, GOT2). The Mitochondrial Malate Aspartate Shuttle (MAS) We conclude that patients with MAS-/MPC1-defects are amenable to dietary intervention and that early (genetic) diagnosis is key for initiation of proper treatment and can even be lifesaving.ġ.2. Six citrin-deficient individuals received a carbohydrate-restricted/fat-enriched diet and showed normalisation of laboratory values/hepatopathy as well as age-adequate thriving. Two individuals with citrin deficiency deceased before the correct diagnosis was established, presumably due to high-carbohydrate treatment. Of 13 MAS/MPC1-individuals with a neurological phenotype treated with KD, 11 experienced benefits-mainly a striking effect against seizures. We here describe 40 (18 previously unreported) subjects with MAS-/MPC1-defects (32 neurological phenotypes, eight citrin deficiency), describe and discuss their phenotypes and genotypes (presenting 12 novel variants), and the efficacy of KD. The same holds for mitochondrial pyruvate carrier (MPC) 1 deficiency, which also presents neurological deficits. Ketogenic diets (KD) are high-fat/low-carbohydrate diets, which decrease glycolysis thus bypassing the mentioned defects. Human disease has been associated with defects in four MAS-proteins (encoded by MDH1, MDH2, GOT2, SLC25A12) sharing a neurological/epileptic phenotype, as well as citrin deficiency ( SLC25A13) with a complex hepatopathic-neuropsychiatric phenotype. The mitochondrial malate aspartate shuttle system (MAS) maintains the cytosolic NAD+/NADH redox balance, thereby sustaining cytosolic redox-dependent pathways, such as glycolysis and serine biosynthesis. You'll also come across upper case gamma (Γ) as a variable, or as a function name. See Math of Beauty.) The first 3 letters of the Greek alphabet, α (alpha), β (beta) and γ (gamma) are also used in trigonometry as variables for angles. 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