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Malonyl-CoAMalonyl CoA is a small molecule synthesized in cells by acetyl CoA carboxylase. Malonyl CoA has an important role in regulating muscle fatty acid oxidation, secondary to inhibiting mitochondrial fatty acid uptake. It also is an important substrate for fatty acid biosynthesis. Malonyl CoA decarboxylase (MCD)MCD is an enzyme that controls malonyl CoA levels in a number of different types of cells, particularly heart and skeletal muscle. MCD degrades malonyl CoA to acetyl CoA. This is an important reaction, since malonyl CoA is a potent inhibitor of mitochondrial fatty acid uptake, and therefore an important regulator of muscle fatty acid oxidation. MalonyldialdehydeMalonydialdehyde is a small molecule that is released from larger molecules, such as lipids, during oxidative stress. Measurement of the release of this compound is often used as an index of the degree of free radical oxidative stress to which a cell or organ is being exposed. Mannose-6-phosphateMannose-6-phosphate is a sugar that is phosphorylated on its sixth carbon. Matrix metalloproteinase (MMP)Matrix metalloproteinase (MMP) is a extracellular matrixdegrading enzyme that is involved in tissue remodeling. Alteration in MMP activity have been shown to contribute to heart remodeling in heart failure or following an acute myocardial infarction. Membrane phospholipid turnoverCellular membranes consist of a number of phospholipids that are arranged in a bilayer. There are a number of different phospholipids in these membranes. These phospholipids are not static and are constantly turning over. Some phospholipids, such as phosphatidyl inositol, can turnover quite rapidly, resulting in the production of products that are important in cellular signalling processes (i.e. inositol triphosphate and diacylglycerol). Missense mutationMutations in the nucleotide sequence of DNA can result in the coding of proteins with missense mutations in the amino acids. This can alter the primary amino acid sequence and protein structure of the protein. An example of missense mutations are mutations of the b-myosin heavy chain (MHC) gene that can lead in a number of mutations in the protein that can lead to hypertrophic cardiomyopathy. Mitochondrial electron transport chainThe mitochondrial electron transport chain is a number of mitochondrial proteins involved in energy production. Nicotinamide adenine dinucleotide (NADH) and reduced flavin adenine dinucleotide (FADH2) are used as substrates for the electron transport chain. In the course of oxidizing NADH and FADH2, protons are pumped out of the mitochondria. This sets up an electrochemical gradient in which adenosine diphosphate is phosphorylated to adenosine triphosphate (ATP) (by an ATP synthase) as protons flow back into the mitochondria. Mitochondrial K+-ATP channelsMitochondrial ATP-sensitive potassium (KATP) channels are potassium channels that are present in the mitochondrial membrane of cells. These channels are inhibited by ATP. The opening of the mitochondrial ATPsensitive K(+) (KATP) channels in the heart is believed to have cardioprotective effects in the setting of ischemia and ischemia and reperfusion. Despite a major research effort, the molecular characterization of the mitochondrial K+-ATP channel remains unknown. Mitochondrial thioredoxinThioredoxin is an antioxidant enzyme that prevents the oxidation of thiol (sulfur) groups of proteins. Mitogen-activated protein kinase (MAPK)Mitogen-activated protein kinase (MAPK) is one of the kinases in the MAPK superfamily. This kinase pathway is engaged by phosphorylation in response to environmental stress signals and has many cellular actions, including a role in cell proliferation. Mitogen-activated protein kinase (MAPK) cascadeThe MAPK cascade involves a number of kinases that have diverse functions in cells. The inflammatory effects of tumor necrosis factor (TNF)-α in cells is mediated by signaling pathways involving MAPK’s. pathways. MAP-KAPK-1 (also known as p90 ribosomal S6 kinase, p90rsk). The mitogen-activated protein kinase (MAPK)-activated kinase, p90 ribosomal S6 kinase is a kinase in the MAPK cascade. p90 ribosomal S6 kinase is activated by phosphorylation, whereby it then participates in many cellular processes, including the regulation of protein synthesis. MonobutyrinMonobutryin is a novel angiogenic compound that is synthesized and secreted during the differentiation of adipocytes. It has a major role as a differentiationdependent angiogenic molecule. MyoglobinMyoglobin is an important intracellular oxygen binding hemoprotein found in abundance in heart and skeletal muscle. Myoglobin not only provides oxygen for mitochondrial oxidative metabolism, it also buffers intracellular oxygen during changes in mitochondrial oxygen demand. MyosinMyosin is one of the two main proteins involved in muscle
contraction. It is a large protein that interacts with actin to
form the muscle striations typical of muscle fibers. Sliding
of myosin by actin is an important step in muscle
contraction. ![]() Myosin heavy chainMyosin heavy chain is a key component of the contractile apparatus of muscle cells and comprises the thick filament of muscle fibers. Sliding of myosin by actin (another major structure of contractile proteins) is an important step in muscle contraction. Na+/H+ exchangerThe Na+/H+ exchanger is a membrane ion transporter that exchanges Na+ for H+. In the heart, it is one of a number of pathways to extrude protons (H+) from the heart. However, this is coupled with a net inward flux of Na+. During and following ischemia, Na+/H+ exchanger activity increases, due to the ischemic-induced increase in intracellular acidosis. The increased Na+/H+ exchanger activity can lead to Na+ overload in the ischemic heart, which can decrease cardiac efficiency (energy is needed to extrude this Na+) and contribute to cell injury. Na/K-ATPase and the SR-Ca++-ATPaseNa/K-ATPase and the SR-Ca++-ATPase are two ion pumps
that are involved in the transport of ions across
membranes. They usually pump these ions against a
concentration gradient, and therefore energy is required,
which is provided by the hydrolysis of ATP, the main energy
currency in cells (hence the name ATPases). Na/K-ATPase
pumps Na+ out of cells, while simultaneously pumping K+
into cells. The SR-Ca++-ATPase pumps Ca++ from the
cytoplasm into sarcoplasmic reticulum vesicles. In
muscle, this results in a lowering of cytoplasmic calcium
and a relaxation of the muscle. ![]() Nicotinamide adenine dinucleotide (NADH)- coenzyme Q-oxidoreductase complex (complex I)Nicotinamide adenine dinucleotide (NADH)-coenzyme Qoxidoreductase complex (complex I) is the first complex of the electron transport chain. It oxidizes NADH in the first reaction of the electron transport chain. Nicotinamide adenine dinucleotide (NADH) and the electron transport chainNicotinamide adenine dinucleotide (NADH) is an important molecule that is both a substrate and a product of many biochemical reactions. In mitochondria, the production of NADH by the catabolism of fatty acids and carbohydrates enters the electron transport chain. The electron transport chain transfers electrons through a number of different enzyme complexes which catalyze the pumping of protons out of the mitochondrial matrix. These protons can then pass back into the mitochondria via an enzyme called ATP synthase. The downhill electrochemical gradient of this process produces energy that results in the production of ATP from ADP. ATP is a form of chemical energy used in most cellular processes requiring energy. NIH 3T3 fibroblastsNIH 3T3 fibroblasts are a commonly used fibroblast cell line that was produced by the National Institutes of Health. Nitric oxide activates guanylyl cyclaseGuanylyl cyclase is the enzyme responsible for converting guanylyl triphosphate to cyclic guanosine monophosphate (cGMP). One of the prominent effects of cGMP is smooth muscle relaxation. Release of nitric oxide by endothelial cells is a potent vasodilator. The actions of nitric oxide are now known to be due to a stimulation of guanylyl cyclase, that results in an increase in cGMP levels and smooth muscle relaxation. Nitric oxide synthaseNitric oxide synthase is the enzyme responsible for the production of nitric oxide (NO). NO is a very important molecule in many cellular events and was identified as the molecule released by endothelial cells that can cause vascular relaxation. NociceptorA nociceptor is a receptor organ that is sensitive to stimuli capable of causing harm or injury. In response to the stimuli, the receptor would provide the sensation of pain (via neural transmission of the sensory stimulus from the receptor to the brain). Nuclear transcription factor kappa-B (NFk-B)NFk-B is a ubiquitous transcription factor that plays an important integrating role in the intracellular regulation of immune response, inflammation and cell cycle regulation. NFk-B is activated by various stimuli, such as those that are implicated in the progression of chronic heart failure. Signaling by NFk-B involves its release from inhibitor kappa B (IkappaB) in the cytosol, followed by translocation into the nucleus, where it affects gene transcription. NucleasesNucleases are nuclear enzymes involved in the degradation of nucleic acids chains. NucleoplasmThe nucleoplasm is the protoplasm of a cell contained within the nucleus. It is the compartment of the cell that contains the nuclear material, such as the chromosomes. Ob/ob mouseThe leptin-deficient (ob/ob) mouse is a genetically mutated mouse in which a leptin deficiency occurs. This leptin deficiency results in the development of a marked obesity, glucose intolerance and insulin-resistance. It is a very common experimental model in which to examine the consequences of leptin deficiency on obesity and insulinresistance. 8-OH-deoxyguanosine (8-OHdG)8-OH-deoxyguanosine (8-OHdG) is produced when DNA is subjected to free radical attack. Leukocyte DNA 8-OHdG levels are sometimes used as a measure of free radical injury to DNA. Orthophenylpentadecanoic acid (oPPA)Orthophenylpentadecanoic acid (oPPA) is a fatty acid analog that can be radiolabeled (eg. with 123I) and used as an imaging agent to assess fatty acid uptake into tissues. It is often used to determine whether fatty acid uptake is altered in the hearts of patients. This is established by using a gamma-camera to determine the amount of radiolabeled oPPA taken up by the heart. Oxygen radical scavenger enzymesOxygen-derived free radicals are highly reactive compounds that can react with and damage cellular components (lipid membranes, protein, and DNA/RNA). In order to protect the cell from these oxygen-derived free radicals, cells have a number of different oxygen radical scavenger enzymes that are used to neutralize these free radicals. OxysterolsOxyterols are oxygenated derivatives of cholesterol. They have diverse biological activities, including binding to SREBP-1c and LXRs. |
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