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Inborn Errors Of Lipid Metabolism
Numerous genetic disorders are caused by errors in fatty acid metabolism. These disorders may be described as fatty oxidation disorders or as a ''lipid storage disorders'', and are any one of several inborn errors of metabolism that result from enzyme defects affecting the ability of the body to oxidize fatty acids in order to produce energy within muscles, liver, and other cell types. Some of the more common fatty acid metabolism disorders are: Coenzyme A dehydrogenase deficiencies * Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD) - Very long-chain acyl-coenzyme A dehydrogenase * Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (LCHAD) - Long-chain 3-hydroxyacyl-coenzyme A * Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD) - Medium-chain acyl-coenzyme A dehydrogenase * Short-chain acyl-coenzyme A dehydrogenase deficiency (SCAD) - Short-chain acyl-coenzyme A dehydrogenase * 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADH) - 3-hydroxy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Genetic Disorders
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders are the most common, the term is mostly used when discussing disorders with a single genetic cause, either in a gene or chromosome. The mutation responsible can occur spontaneously before embryonic development (a ''de novo'' mutation), or it can be inherited from two parents who are carriers of a faulty gene ( autosomal recessive inheritance) or from a parent with the disorder ( autosomal dominant inheritance). When the genetic disorder is inherited from one or both parents, it is also classified as a hereditary disease. Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA (due to their size). There are well over 6,000 known ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
3-hydroxyacyl-coenzyme A Dehydrogenase
In enzymology, a 3-hydroxyacyl-CoA dehydrogenase () is an enzyme that catalyzes the chemical reaction :(S)-3-hydroxyacyl-CoA + NAD+ \rightleftharpoons 3-oxoacyl-CoA + NADH + H+ Thus, the two substrates of this enzyme are (S)-3-hydroxyacyl-CoA and NAD+, whereas its 3 products are 3-oxoacyl-CoA, NADH, and H+. This enzyme belongs to the family of oxidoreductases, to be specific those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. Isozymes In humans, the following genes encode proteins with 3-hydroxyacyl-CoA dehydrogenase activity: * HADH – Hydroxyacyl-Coenzyme A dehydrogenase * HSD17B10 – 3-Hydroxyacyl-CoA dehydrogenase type-2 * EHHADH – Peroxisomal bifunctional enzyme * HSD17B4 – Peroxisomal multifunctional enzyme type 2 Function 3-Hydroxyacyl CoA dehydrogenase is classified as an oxidoreductase. It is involved in fatty acid metabolic processes. Specifically it catalyzes the third step of beta oxidation; the oxidation of L-3-hydroxya ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carnitine Palmitoyltransferase II Deficiency
Carnitine palmitoyltransferase II deficiency is an autosomal recessively inherited genetic metabolic disorder characterized by an enzymatic defect that prevents long-chain fatty acids from being transported into the mitochondria for utilization as an energy source. The disorder presents in one of three clinical forms: lethal neonatal, severe infantile hepatocardiomuscular and myopathic. First characterized in 1973 by DiMauro and DiMauro the adult myopathic form of this disease is triggered by physically strenuous activities and/or extended periods without food and leads to immense muscle fatigue and pain. It is the most common inherited disorder of lipid metabolism affecting the skeletal muscle of adults, primarily affecting males. CPT II deficiency is also the most frequent cause of hereditary myoglobinuria. Signs and symptoms The three main types of carnitine palmitoyltransferase II deficiency classified on the basis of tissue-specific symptomatology and age of onset. Among t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carnitine Palmitoyltransferase I
Carnitine palmitoyltransferase I (CPT1) also known as carnitine acyltransferase I, CPTI, CAT1, CoA:carnitine acyl transferase (CCAT), or palmitoylCoA transferase I, is a mitochondrial enzyme responsible for the formation of acyl carnitines by catalyzing the transfer of the acyl group of a long-chain fatty acyl-CoA from coenzyme A to l-carnitine. The product is often Palmitoylcarnitine (thus the name), but other fatty acids may also be substrates. It is part of a family of enzymes called carnitine acyltransferases. This "preparation" allows for subsequent movement of the acyl carnitine from the cytosol into the intermembrane space of mitochondria. Three isoforms of CPT1 are currently known: CPT1A, CPT1B, and CPT1C. CPT1 is associated with the outer mitochondrial membrane. This enzyme can be inhibited by malonyl CoA, the first committed intermediate produced during fatty acid synthesis. Its role in fatty acid metabolism makes CPT1 important in many metabolic disorders such as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carnitine Palmitoyltransferase I Deficiency
Carnitine palmitoyltransferase I deficiency is a rare metabolic disorder that prevents the body from converting certain fats called long-chain fatty acids(LCFA) into energy, particularly during periods without food. It is caused by a mutation in CPT1A on chromosome 11. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. People with this disorder have a faulty enzyme, carnitine palmitoyltransferase I, that prevents these long-chain fatty acids from being transported into the mitochondria to be broken down. Symptoms and signs Signs and symptoms of this disorder include low levels of ketones (hypoketosis) and low blood sugar (hypoglycemia). Together these signs are called hypoketotic hypoglycemia. People with this disorder typically also have an enlarged liver (hepatomegaly), muscle weakness, and elevated levels of carnitine in the blood. Genetics Mutations in the ''CPT1A'' gene cause carnitine palmitoyltransferase I ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carnitine-acylcarnitine Translocase
Carnitine-acylcarnitine translocase (CACT) is responsible for passive transport of carnitine and carnitine-fatty acid complexes and across the inner mitochondrial membrane as part of the carnitine shuttle system. Function Fatty acyl–carnitine can diffuse from the cytosol across the porous outer mitochondrial membrane to the intermembrane space, but must utilize CACT to cross the nonporous inner mitochondrial membrane and reach the mitochondrial matrix. CACT is a cotransporter, returning one molecule of carnitine from the matrix to the intermembrane space as one molecule of fatty acyl–carnitine moves into the matrix. Clinical significance A disorder is associated with carnitine-acylcarnitine translocase deficiency. This disorder disrupts the carnitine shuttle system from moving fatty acids across the mitochondrial membrane, leading to a decrease in fatty acid catabolism. The result is an accumulation of fatty acid within muscles and liver, decreased tolerance to long term ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carnitine-acylcarnitine Translocase Deficiency
Carnitine-acylcarnitine translocase deficiency is a rare, autosomal recessive metabolic disorder that prevents the body from converting long-chain fatty acids into energy, particularly during periods without food. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. People with this disorder have a faulty enzyme that prevents long-chain fatty acids from being transported into the innermost part of the mitochondria for processing. Presentation The signs of carnitine-acylcarnitine translocase deficiency usually begin within the first few hours of life. Seizures, an irregular heartbeat, and breathing problems are often the first signs of this disorder. This disorder may also cause extremely low levels of ketones (products of fat breakdown that are used for energy) and low blood sugar (hypoglycemia). Together, these two signs are called hypoketotic hypoglycemia. Other signs that are often present include ammonia in t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SLC22A5
SLC22A5 is a membrane transport protein associated with primary carnitine deficiency. This protein is involved in the active cellular uptake of carnitine. It acts a symporter, moving sodium ions and other organic cations across the membrane along with carnitine. Such polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for the elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. Mutations in the ''SLC22A5'' gene cause systemic primary carnitine deficiency, which can lead to heart failure. Structure The ''SLC22A5'' gene, containing 10 exons,Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: : : . World Wide Web URL: https://omim.org/ is located on the q arm of chromosome 5 in position 31.1 and spans 25,910 base pair. The gene produces a 63 kDa protein composed of 557 amino acids. The protein has 12 putative transmembran ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Primary Carnitine Deficiency
Systemic primary carnitine deficiency (SPCD)Systemic primary carnitine deficiency is an inborn error of fatty acid transport caused by a defect in the transporter responsible for moving carnitine across the plasma membrane. Carnitine is an important amino acid for fatty acid metabolism. When carnitine cannot be transported into tissues, |
Malonyl-CoA Decarboxylase
Malonyl-CoA decarboxylase (), (which can also be called MCD and malonyl-CoA carboxyl-lyase) is found in bacteria and humans and has important roles in regulating fatty acid metabolism and food intake, and it is an attractive target for drug discovery. It is an enzyme associated with Malonyl-CoA decarboxylase deficiency. In humans, it is encoded by the MLYCD gene. Its main function is to catalyze the conversion of malonyl-CoA into acetyl-CoA and carbon dioxide. It is involved in fatty acid biosynthesis. To some degree, it reverses the action of Acetyl-CoA carboxylase. Structure MCD presents two isoforms which can be transcribed form one gene: a long isoform (54kDa), distributed in mitochondria, and a short isoform (49kDa) that can be found in peroxisomes and cytosol. The long isoform includes a sequence of signaling towards mitochondria in the N-terminus; whereas the short one only contains the typical sequence of peroxisomal signaling PTS1 in the C-terminus, also shared by the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Malonyl-CoA Decarboxylase Deficiency
Malonyl-CoA decarboxylase deficiency (MCD) is an autosomal-recessive metabolic disorder caused by a genetic mutation that disrupts the activity of Malonyl-CoA decarboxylase. This enzyme breaks down Malonyl-CoA (a fatty acid precursor and a fatty acid oxidation blocker) into acetyl-CoA and carbon dioxide. Signs and symptoms The signs and symptoms of this disorder typically appear in early childhood. Almost all affected children have delayed development. Additional signs and symptoms can include weak muscle tone (hypotonia), seizures, diarrhea, vomiting, and low blood sugar (hypoglycemia). A heart condition called cardiomyopathy, which weakens and enlarges the heart muscle, is another common feature of malonyl-CoA decarboxylase deficiency. Some common symptoms in Malonyl-CoA decarboxylase deficiency, such as cardiomyopathy and metabolic acidosis, are triggered by the high concentrations of Malonyl-CoA in the cytoplasm. High levels of Malonyl-CoA will inhibit β-oxidation of fatty ac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
3-hydroxy-3-methylglutaryl-CoA Lyase
3-Hydroxy-3-methylglutaryl-CoA lyase (or HMG-CoA lyase) is an enzyme ( that in human is encoded by the HMGCL gene located on chromosome 1. It is a key enzyme in ketogenesis (ketone body formation). It is a ketogenic enzyme in the liver that catalyzes the formation of acetoacetate from HMG-CoA within the mitochondria. It also plays a prominent role in the catabolism of the amino acid leucine. Structure The HMGCL gene encodes a 34.5-kDa protein that is localized to the mitochondrion and peroxisome. Multible isoforms of the proteins are known due to alternative splicing. The major isoform (isoform 1) is most highly expressed in the liver whereas isoform 2 is found in energy-demanding tissues including the brain, heart, and skeletal muscle. Structure of the HMGCL protein has been resolved by X-ray crystallography at 2.1-Å resolution, and reveals that the protein may function as a dimer. Substrate access to the active site of the HMGCL enzyme involves substrate binding ac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
