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Citrate–malate Shuttle
The citrate-malate shuttle is a series of chemical reactions, commonly referred to as a biochemical cycle or system, that transports acetyl-CoA in the mitochondrial matrix across the inner and outer mitochondrial membranes for fatty acid synthesis. Mitochondrion, Mitochondria are enclosed in a double membrane. As the inner mitochondrial membrane is impermeable to acetyl-CoA, the shuttle system is essential to fatty acid synthesis in the cytosol. It plays an important role in the generation of lipids in the liver (hepatic lipogenesis). The name of the citrate-malate shuttle is derived from the two Reaction intermediate, intermediates – short-lived chemicals that are generated in a reaction step and consumed entirely in the next – citrate and malate that carry the acetyl-CoA molecule across the mitochondrial double membrane. The citrate–malate shuttle is present in humans and other higher eukaryotic organisms and is closely related to the Krebs cycle. The system is responsib ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oxaloacetate
Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes that occur in animals. It takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, fatty acid synthesis and the citric acid cycle. Properties Oxaloacetic acid undergoes successive deprotonations to give the dianion: :HO2CC(O)CH2CO2H −O2CC(O)CH2CO2H + H+, pKa = 2.22 :−O2CC(O)CH2CO2H −O2CC(O)CH2CO2− + H+, pKa = 3.89 At high pH, the enolizable proton is ionized: :−O2CC(O)CH2CO2− −O2CC(O−)CHCO2− + H+, pKa = 13.03 The enol forms of oxaloacetic acid are particularly stable. Keto-enol tautomerization is catalyzed by the enzyme oxaloacetate tautomerase. ''trans''-Enol-oxaloacetate also appears when tartrate is the substrate for fumarase. Biosynthesis Oxaloacetate forms ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hypoxia (medical)
Hypoxia is a condition in which the body or a region of the body is deprived of an adequate oxygen supply at the tissue (biology), tissue level. Hypoxia may be classified as either ''Generalized hypoxia, generalized'', affecting the whole body, or ''local'', affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise. Hypoxia differs from hypoxemia and anoxemia, in that hypoxia refers to a state in which oxygen present in a tissue or the whole body is insufficient, whereas hypoxemia and anoxemia refer specifically to states that have low or no Oxygen saturation (medicine), oxygen in the blood. Hypoxia in which there is complete absence of oxygen supply is referred to as anoxia. Hypoxia can be due to external causes, when the breathing gas is hypoxic, or internal causes, such as reduced effectiveness of gas transfer in the lung ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Warburg Effect (oncology)
In oncology, the Warburg effect () is the observation that most cancers use aerobic glycolysis and lactic acid fermentation for energy generation rather than the mechanisms used by non-cancerous cells. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The existence of the Warburg effect has fuelled popular misconceptions that cancer can be treated by dietary reductions in sugar and carbohydrate. In fermentation, the last product of glycolysis, pyruvate, is converted into lactate (lactic acid fermentation) or ethanol ( alcoholic fermentation). While fermentation produces adenosine triphosphate (ATP) only in low yield compared to the citric acid cycle and oxidative phosphorylation of aerobic respiration, it allows proliferating cells to convert nutrients such as glucose and glutamine more efficiently into biomass by avoiding unnecessary ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Malate Dehydrogenase 2
Malate dehydrogenase, mitochondrial also known as malate dehydrogenase 2 is an enzyme that in humans is encoded by the ''MDH2'' gene. Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the mitochondria and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria. Structure The protein encoded by MDH2 exists as a dimer, which indicate the important connection between protein stability and enzymatic activity. Each subunit contains two structurally and functionally distinct domains. The first is the NAD-binding domain, which exists in the amino-terminal half of each molecule, and contains a parallel-sheet structure, otherwise known as a Rosman fold motif. The core dinucleotide binding structure is composed of four beta-sheets and one alpha-helix. The other dom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MDH1
Malate dehydrogenase, cytoplasmic also known as malate dehydrogenase 1 is an enzyme that in humans is encoded by the MDH1 gene. Function Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the cytoplasm and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. Regulation The acetylation of MDH1 activates its enzymatic activity and enhance intracellular levels of NADPH, which promotes adipogenic differentiation. Methylation on arginine 248 (R248) negatively regulates MDH1. Protein arginine methyltransferase 4 (PRMT4/CARM1) methylates and inhibits MDH1 by disrupting its dimerization. Arginine methylation of MDH1 represses mitochondria respiration and inhib ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mitochondrial Membrane Transport Protein
Mitochondrial membrane transport proteins, also known as mitochondrial carrier proteins, are proteins which exist in the membranes of mitochondria. They serve to transport molecules and other factors, such as ions, into or out of the organelles. Mitochondria contain both an inner and outer membrane, separated by the inter-membrane space, or inner boundary membrane. The outer membrane is porous, whereas the inner membrane restricts the movement of all molecules. The two membranes also vary in membrane potential and pH. These factors play a role in the function of mitochondrial membrane transport proteins. There are 53 discovered human mitochondrial membrane transporters, with many others that are known to still need discovered. Mitochondrial outer membrane The outer mitochondrial membrane forms the border of mitochondria towards the cellular environment. The outer membrane mitochondrial proteins carry out functions for mitochondrial biogenesis and integration between mitochondria ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Metabolic Pathway
In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes. In most cases of a metabolic pathway, the product (chemistry), product of one enzyme acts as the substrate (chemistry), substrate for the next. However, side products are considered waste and removed from the cell. Different metabolic pathways function in the position within a Eukaryotic Cell, eukaryotic cell and the significance of the pathway in the given compartment of the cell. For instance, the electron transport chain and oxidative phosphorylation all take place in the mitochondrial membrane. In contrast, glycolysis, pentose phosphate pathway, and Fatty acid synthesis, fatty acid biosynthesis all occur in the cytosol of a cell. There are two types of metabolic pathw ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pyruvate Dehydrogenase Complex
Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this complex links the glycolysis metabolic pathway to the citric acid cycle. Pyruvate decarboxylation is also known as the "pyruvate dehydrogenase reaction" because it also involves the oxidation of pyruvate. The levels of pyruvate dehydrogenase enzymes play a major role in regulating the rate of carbohydrate metabolism and are strongly stimulated by the evolutionarily ancient hormone insulin. The PDC is opposed by the activity of pyruvate dehydrogenase kinase, and this mechanism plays a pivotal role in regulating rates of carbohydrate and lipid metabolism in many physiological states across taxa, including feeding, starvation, diabetes mellitus, hyperthyroidism, and hibernation. The multi-enzyme complex is related structurally and fun ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
β-oxidation
In biochemistry and metabolism, beta oxidation (also β-oxidation) is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA. Acetyl-CoA enters the citric acid cycle, generating NADH and FADH2, which are electron carriers used in the electron transport chain. It is named as such because the beta carbon of the fatty acid chain undergoes oxidation and is converted to a carbonyl group to start the cycle all over again. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes. The overall reaction for one cycle of beta oxidation is: :C''n''-acyl-CoA + FAD + NAD''+'' + H''2''O + CoA → C''n''-2-acyl-CoA + FADH''2'' + NADH + H''+'' + acetyl-CoA Activation and membrane transport Free fatty acids cannot penetrate any biologi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The Thermodynamic free energy, free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and NADH, reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes. The wide occurrence of glycolysis in other species indicates that it is an ancient metabolic pathway. Indeed, the reactions that make up glycolysis and its parallel pathway, the pentose phosphate pathway, can occur in the Great Oxygenation Event, oxygen-free conditions of the Archean oceans, also in the absence of enzymes, catalyzed by metal ions, meaning this is a plausible prebiotic pathway for abiogenesis. The most common type of glycolysis is the ''Embden–Meyerhof–Parnas (EMP) pathway'', which was discovered by Gustav Embden, Otto Meyerhof, and Jakub Kar ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pyruvate Decarboxylation
Pyruvate decarboxylation or pyruvate oxidation, also known as the link reaction (or oxidative decarboxylation of pyruvate), is the conversion of pyruvate into acetyl-CoA by the enzyme complex pyruvate dehydrogenase complex. The reaction may be simplified as: :Pyruvate + NAD+ + CoA → Acetyl-CoA + NADH + CO2 Pyruvate oxidation is the step that connects glycolysis and the Krebs cycle. In glycolysis, a single glucose molecule (6 carbons) is split into 2 pyruvates (3 carbons each). Because of this, the link reaction occurs twice for each glucose molecule to produce a total of 2 acetyl-CoA molecules, which can then enter the Krebs cycle. Energy-generating ions and molecules, such as amino acids and carbohydrates, enter the Krebs cycle as acetyl coenzyme A and oxidize in the cycle. The pyruvate dehydrogenase complex (PDC) catalyzes the decarboxylation of pyruvate, resulting in the synthesis of acetyl-CoA, CO2, and NADH. In eukaryotes, this enzyme complex regulates pyruvate met ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
