query: the process of changing fatty acids to several molecules of acetyl coa is called

pos: Metabolism to free fatty acids and glycerol. The glycerol enters glycolysis and the fatty acids are broken down by beta oxidation to release acetyl-CoA, which then is fed into the citric acid cycle. Fatty acids release more energy upon oxidation than carbohydrates because carbohydrates contain more oxygen in their structures. Steroids are also broken down by some bacteria in a process similar to beta oxidation, and this breakdown process involves the release of significant amounts of acetyl-CoA, propionyl-CoA, and pyruvate, which can all be used by the cell for energy. "M. tuberculosis" can also grow on the lipid cholesterol as a

pos: Citric acid cycle fatty acids are broken down through a process known as beta oxidation, which results in the production of mitochondrial "acetyl-CoA", which can be used in the citric acid cycle. Beta oxidation of fatty acids with an odd number of methylene bridges produces propionyl-CoA, which is then converted into "succinyl-CoA" and fed into the citric acid cycle as an anaplerotic intermediate. The total energy gained from the complete breakdown of one (six-carbon) molecule of glucose by glycolysis, the formation of 2 "acetyl-CoA" molecules, their catabolism in the citric acid cycle, and oxidative phosphorylation equals about 30 ATP molecules, in eukaryotes. The

pos: Acyl-CoA Acyl-CoA Acyl-CoA is a group of coenzymes involved in the metabolism of fatty acids. It is a temporary compound formed when coenzyme A (CoA) attaches to the end of a long-chain fatty acid inside living cells. The compound undergoes beta oxidation, forming one or more molecules of acetyl-CoA. This, in turn, enters the citric acid cycle, eventually forming several molecules of ATP. To be oxidatively degraded, a fatty acid must first be activated in a two-step reaction catalyzed by acyl-CoA synthetase. First, the fatty acid displaces the diphosphate group of ATP, then coenzyme A (HSCoA) displaces the AMP group to

pos: Acyl-CoA cytosol, but oxidation occurs in the mitochondria. Because there is no transport protein for CoA adducts, acyl groups must enter the mitochondria via a shuttle system involving the small molecule carnitine. Acyl-CoA Acyl-CoA is a group of coenzymes involved in the metabolism of fatty acids. It is a temporary compound formed when coenzyme A (CoA) attaches to the end of a long-chain fatty acid inside living cells. The compound undergoes beta oxidation, forming one or more molecules of acetyl-CoA. This, in turn, enters the citric acid cycle, eventually forming several molecules of ATP. To be oxidatively degraded, a fatty acid

pos: Metabolism to free fatty acids and glycerol. The glycerol enters glycolysis and the fatty acids are broken down by beta oxidation to release acetyl-CoA, which then is fed into the citric acid cycle. Fatty acids release more energy upon oxidation than carbohydrates because carbohydrates contain more oxygen in their structures. Steroids are also broken down by some bacteria in a process similar to beta oxidation, and this breakdown process involves the release of significant amounts of acetyl-CoA, propionyl-CoA, and pyruvate, which can all be used by the cell for energy. "M. tuberculosis" can also grow on the lipid cholesterol as a

pos: Lipid metabolism steps of fatty acids catabolism occur in the mitochondria. Long chain fatty acids (more than 14 carbon) need to be converted to Fatty acyl-CoA in order to pass across the mitochondria membrane. Fatty acid catabolism begins in the cytoplasm of cells as Acyl-CoA synthetase uses the energy from cleavage of an ATP to catalyze the addition of Coenzyme A to the fatty acid. The resulting Acyl-CoA cross the mitochondria membrane and enter the process of beta oxidation. The main products of the beta oxidation pathway are Acetyl-CoA (which is used in the Citric acid cycle to produce energy), NADH and

pos: Ackee only in the seeds. These two molecules are converted in the body to methylene cyclopropyl acetic acid (MCPA). Hypoglycin A and MCPA are both toxic. MCPA and hypoglycin A inhibit several enzymes involved in the breakdown of acyl CoA compounds, often binding irreversibly to coenzyme A, carnitine and carnitine acyltransferases I and II, reducing their bioavailability and consequently inhibiting beta oxidation of fatty acids. Beta oxidation normally provides the body with ATP, NADH, and acetyl CoA which is used to supplement the energy produced by glycolysis. Glucose stores are consequently depleted leading to hypoglycemia. Clinically, this condition is called Jamaican

pos: Beta oxidation Beta oxidation In biochemistry and metabolism, beta-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, which enters the citric acid cycle, and NADH and FADH, which are co-enzymes used in the electron transport chain. It is named as such because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group. 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

pos: Fatty acid synthesis g is locked inside the skeletal muscles and is unavailable to the body as a whole. The 100 g or so of glycogen stored in the liver is depleted within one day of starvation. Thereafter the glucose that is released into the blood by the liver for general use by the body tissues, has to be synthesized from the glucogenic amino acids and a few other gluconeogenic substrates, which do not include fatty acids. Fatty acids are broken down to acetyl-CoA by means of beta oxidation inside the mitochondria, whereas fatty acids are synthesized from acetyl-CoA outside the mitochondrion, in

pos: Fatty acid metabolism Thereafter the glucose that is released into the blood by the liver for general use by the body tissues, has to be synthesized from the glucogenic amino acids and a few other gluconeogenic substrates, which do not include fatty acids. Please note however that lipolysis releases glycerol which can enter the pathway of gluconeogenesis. Fatty acids are broken down to acetyl-CoA by means of beta oxidation inside the mitochondria, whereas fatty acids are synthesized from acetyl-CoA outside the mitochondria, in the cytosol. The two pathways are distinct, not only in where they occur, but also in the reactions that occur,

pos: Beta oxidation overall reaction for one cycle of beta oxidation is: Fatty acid catabolism consists of: Free fatty acids cannot penetrate any biological membrane due to their negative charge. Free fatty acids must cross the cell membrane through specific transport proteins, such as the SLC27 family fatty acid transport protein. Once in the cytosol, the following processes bring fatty acids into the mitochondrial matrix so that beta-oxidation can take place. Once the fatty acid is inside the mitochondrial matrix, beta-oxidation occurs by cleaving two carbons every cycle to form acetyl-CoA. The process consists of 4 steps. Fatty acids are oxidized by most

pos: Citric acid cycle number of ATP molecules derived from the beta oxidation of a 6 carbon segment of a fatty acid chain, and the subsequent oxidation of the resulting 3 molecules of "acetyl-CoA" is 40. In this subheading, as in the previous one, the TCA intermediates are identified by "italics". Several of the citric acid cycle intermediates are used for the synthesis of important compounds, which will have significant cataplerotic effects on the cycle. "Acetyl-CoA" cannot be transported out of the mitochondrion. To obtain cytosolic acetyl-CoA, "citrate" is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the

pos: Glyoxylate cycle place in the TCA cycle, allowing simple carbon compounds to be used in the later synthesis of macromolecules, including glucose. Glyoxylate is subsequently combined with acetyl-CoA to produce malate, catalyzed by MS. Malate is also formed in parallel from succinate by the action of succinate dehydrogenase and fumarase. Fatty acids from lipids are commonly used as an energy source by vertebrates as fatty acids are degraded through beta oxidation into acetate molecules. This acetate, bound to the active thiol group of coenzyme A, enters the "citric acid cycle" (TCA cycle) where it is fully oxidized to carbon dioxide. This pathway

pos: Enoyl-CoA hydratase Enoyl-CoA hydratase Enoyl-CoA hydratase (ECH) or crotonase is an enzyme that hydrates the double bond between the second and third carbons on 2-trans/cis-enoyl-CoA: ECH is essential to metabolizing fatty acids in beta oxidation to produce both acetyl CoA and energy in the form of ATP. ECH of rats is a hexameric protein (this trait is not universal, but human enzyme is also hexameric), which leads to the efficiency of this enzyme as it has 6 active sites. This enzyme has been discovered to be highly efficient, and allows people to metabolize fatty acids into energy very quickly. In fact this

pos: Lipid metabolism FADH. The process of beta oxidation requires the following enzymes: Acyl CoA dehydrogenase, Enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase. The diagram to the left shows how fatty acids are converted into Acetyl-coA. The overall net reaction, using palmitoyl CoA (16:0) as a model substrate is: 7 FAD + 7 NAD + 7 CoASH + 7 HO + H(CHCH)CHCO-SCoA → 8 CHCO-SCoA + 7 FADH + 7 NADH + 7 H In addition to dietary fats, storage lipids stored in the adipose tissues are one of the main sources of energy for living organisms. Triacylglycerols, lipid membrane and cholesterol can

pos: ACAA2 ACAA2 3-Ketoacyl-CoA thiolase, mitochondrial also known as acetyl-Coenzyme A acyltransferase 2 is an enzyme that in humans is encoded by the "ACAA2" gene. Acetyl-Coenzyme A acyltransferase 2 is an acetyl-CoA C-acyltransferase enzyme. The ACAA2 gene encodes a 41.9 kDa protein that is composed of 397 amino acids and contains 88 observed peptides. The encoded protein catalyzes the last step of the mitochondrial fatty acid beta oxidation spiral. Unlike most mitochondrial matrix proteins, it contains a non-cleavable amino-terminal targeting signal. ACAA2 has been shown to be a functional BNIP3 binding partner, which provides a possible link between fatty acid metabolism and

pos: Starvation response mitochondria as an acyl-carnitine via the action of the enzyme CAT-1. This step controls the metabolic flux of beta oxidation. The resulting acetyl-CoA enters the TCA cycle and undergoes oxidative phosphorylation to produce ATP. The body invests some of this ATP in gluconeogenesis to produce more glucose. Triglycerides and long-chain fatty acids are too hydrophobic to cross into brain cells, so the liver must convert them into short-chain fatty acids and ketone bodies through ketogenesis. The resulting ketone bodies, acetoacetate and β-hydroxybutyrate, are amphipathic and can be transported into the brain (and muscles) and broken down into acetyl-CoA for use

pos: Malonyl-CoA decarboxylase acetyl-CoA in peroxisomes. This is due to the fact that the beta oxidation of long chain fatty acids with an odd number of carbons produces propionyl-CoA. Most part of this metabolite is transformed into succinyl-CoA, which is an intermediate of the tricarboxylic acid cycle. The major alternative route by which the propionyl-CoA is metabolized is based on its conversion to acrylyl-CoA. After that, it is converted to 3-hydroxy propionic acid and finally to malonic semi-aldehyde. As soon as malonic semi aldehyde is produced, it is indirectly transformed into acetyl-CoA. This conversion has been detected only in bacteria, in the other

pos: Acetoacetic acid CoA is lost from this yielding acetoacetate. The initial acetoacetate can come from the last cycle in the beta oxidation of a fatty acid, or it can be synthesized from two acetyl CoA molecules, catalyzed by thiolase. In mammals acetoacetate produced in the liver (along with the other two "ketone bodies") is released into the bloodstream as an energy source during periods of fasting, exercise, or as a result of type 1 diabetes mellitus. First a CoA group is enzymatically transferred to it from succinyl CoA, converting it back to acetoacetyl CoA. This is then broken into two acetyl CoA

neg: Fatty acid synthesis Fatty acid synthesis Fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell. Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the glycolytic pathway. The glycolytic pathway also provides the glycerol with which three fatty acids can combine (by means of ester bonds) to form triglycerides (also known as "triacylglycerols" – to distinguish them from fatty "acids" – or simply as "fat"), the final product of the lipogenic process. When only

neg: Lipid triglycerides, sterols, and membrane phospholipids. The process of lipid metabolism synthesizes and degrades the lipid stores and produces the structural and functional lipids characteristic of individual tissues. In animals, when there is an oversupply of dietary carbohydrate, the excess carbohydrate is converted to triglycerides. This involves the synthesis of fatty acids from acetyl-CoA and the esterification of fatty acids in the production of triglycerides, a process called lipogenesis. Fatty acids are made by fatty acid synthases that polymerize and then reduce acetyl-CoA units. The acyl chains in the fatty acids are extended by a cycle of reactions that add the

neg: Fatty-acyl-CoA synthase alpha and beta subunits. The enzyme complex therefore consists of six functional centers for fatty acid synthesis. The enzyme catalyzes the reaction: Acetyl-CoA + n malonyl-CoA + 4n NADPH + 4n H formula_1 long-chain-acyl-CoA + n CoA + n CO + 4n NADP The 4 substrates of this enzyme are acetyl-CoA, malonyl-CoA, NADPH, and H, whereas its 4 products are Acyl-CoA, CoA, CO, and NADP. More specifically, the FAS catalysis mechanism consumes an acetyl-coenzyme A (acetyl-CoA) and seven malonyl-CoA molecules to produce a Palmitoyl-CoA. Synthesis of fatty acids is generally performed by fatty acid synthase (FAS). Though the syntheses of

neg: Odd-chain fatty acid Odd-chain fatty acid Odd chain fatty acids are those that contain an odd number of carbon atoms in the structure. Almost all animal fatty acid synthesis is done by assembling two 2C Acetyl-CoA molecules together. Because the segments are each two carbons in length the resulting fatty acid has an even number of carbon atoms in it. However, propionyl-CoA instead of acetyl-CoA is used as the primer for the synthesis of long-chain fatty acids with an odd number of carbon atoms, which are found particularly in ruminant fat and milk Some plant-based fatty acids, also have an odd number of

neg: Ketone bodies they are broken down into acetyl-CoA units by a sequence of reactions known as β-oxidation. The acetyl-CoA produced by β-oxidation enters the citric acid cycle in the mitochondrion by combining with oxaloacetate to form citrate. This results in the complete combustion of the acetyl group of acetyl-CoA (see diagram above, on the right) to CO and water. The energy released in this process is captured in the form of 1 GTP and 11 ATP molecules per acetyl group (or acetic acid molecule) oxidized. This is the fate of acetyl-CoA wherever β-oxidation of fatty acids occurs, except under certain circumstances in

neg: Fatty acid cytosol where the synthesis of fatty acids occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA, citrate (produced by the condensation of acetyl-CoA with oxaloacetate) is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol. There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to the mitochondrion as malate. The cytosolic acetyl-CoA is carboxylated by acetyl CoA carboxylase into malonyl-CoA, the first committed step in the synthesis of fatty acids. Malonyl-CoA is then involved in a repeating series of reactions that lengthens the growing fatty acid

neg: Lipogenesis the total available energy introduced with food is abundant and not all of it is immediately needed for metabolic processes. Lipogenesis encompasses both the process of fatty acid synthesis and triglyceride synthesis, where fatty acids are esterified to glycerol. Fatty acids are produced in the cytoplasm of cells by repeatedly adding two-carbon units to acetyl-CoA. Triglycerides are produced in the endoplasmic reticulum of cells by bonding three fatty acid molecules to each glycerol molecule. Both processes take place mainly in liver and adipose tissue. Triglicerides produced by liver cells are secreted from the liver in the form of very-low-density lipoproteins

neg: Coenzyme A acids. This process is implemented by regulation of acetyl-CoA carboxylase, which catalyzes the committed step in fatty acid synthesis. Insulin stimulates acetyl-CoA carboxylase, while epinephrine and glucagon inhibit its activity. During cell starvation, coenzyme A is synthesized and transports fatty acids in the cytosol to the mitochondria. Here, acetyl-CoA is generated for oxidation and energy production. In the citric acid cycle, coenzyme A works as an allosteric regulator in the stimulation of the enzyme pyruvate dehydrogenase. New research has found that protein CoAlation plays an important role in regulation of the oxidative stress response. Protein CoAlation plays a similar role

neg: Glycolysis cytosol where the synthesis of fatty acids and cholesterol occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA, citrate (produced by the condensation of acetyl CoA with oxaloacetate) is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol. There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to mitochondrion as malate (and then back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion). The cytosolic acetyl-CoA can be carboxylated by acetyl-CoA carboxylase into malonyl CoA, the first committed step in the synthesis of fatty acids,

neg: Tumor metabolome is produced in mammalian cells is the reaction converting isocitrate to α-ketoglutarate (αKG), which is catalysed by NADP-dependent isocitrate dehydrogenase 1 (IDH1) and IDH2 and have been found linked to tumorigenesis in glioblastoma and acute myeloid leukemia. They are also found to interact with arginine residues required for isocitrate binding in the active site of the proteins of IDH1 and IDH2. Fatty acid synthesis is an anabolic process that starts from the conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase. Malonyl CoA leads to fatty acid synthesis (FAS) and is involved in the elongation of fatty acids through Fatty acid

neg: Malonyl-CoA decarboxylase natural kingdoms there is no scientific evidence to prove it. Malonyl-CoA is an important metabolite in some parts of the cell. In peroxisomes, the accumulation of this substance causes malonic aciduria, a highly pathogenic disease. To avoid it malonyl-CoA decarboxylase (MCD) converts malonyl-CoA into acetyl-CoA through the following reaction: In the cytosol, malonyl-CoA can inhibit the entrance of fatty acids into the mitochondria and it can also act as a precursor for the fatty acids synthesis. Malonyl-CoA also plays an important role inside the mitochondria, where it is an intermediary between fatty acids and acetyl-CoA, which will be a reserve

neg: Fatty acid synthesis glucose. Regulation Acetyl-CoA is formed into malonyl-CoA by acetyl-CoA carboxylase, at which point malonyl-CoA is destined to feed into the fatty acid synthesis pathway. Acetyl-CoA carboxylase is the point of regulation in saturated straight-chain fatty acid synthesis, and is subject to both phosphorylation and allosteric regulation. Regulation by phosphorylation occurs mostly in mammals, while allosteric regulation occurs in most organisms. Allosteric control occurs as feedback inhibition by palmitoyl-CoA and activation by citrate. When there are high levels of palmitoyl-CoA, the final product of saturated fatty acid synthesis, it allosterically inactivates acetyl-CoA carboxylase to prevent a build-up of fatty acids in

neg: Fatty acid metabolism directly. To obtain cytosolic acetyl-CoA, citrate (produced by the condensation of acetyl CoA with oxaloacetate) is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol. There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to mitochondrion as malate (and then converted back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion). The cytosolic acetyl-CoA is carboxylated by acetyl CoA carboxylase into malonyl CoA, the first committed step in the synthesis of fatty acids. Acetyl-CoA is formed into malonyl-CoA by acetyl-CoA carboxylase, at which point malonyl-CoA

neg: Fatty acid synthesis in the liver and adipose tissue, as well as in the mammary glands during lactation. The pyruvate produced by glycolysis is an important intermediary in the conversion of carbohydrates into fatty acids and cholesterol. This occurs via the conversion of pyruvate into acetyl-CoA in the mitochondrion. However, this acetyl CoA needs to be transported into cytosol where the synthesis of fatty acids and cholesterol occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA, citrate (produced by the condensation of acetyl CoA with oxaloacetate) is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol.

neg: Lipid fatty acids are broken down in the mitochondria or in peroxisomes to generate acetyl-CoA. For the most part, fatty acids are oxidized by a mechanism that is similar to, but not identical with, a reversal of the process of fatty acid synthesis. That is, two-carbon fragments are removed sequentially from the carboxyl end of the acid after steps of dehydrogenation, hydration, and oxidation to form a beta-keto acid, which is split by thiolysis. The acetyl-CoA is then ultimately converted into ATP, CO, and HO using the citric acid cycle and the electron transport chain. Hence the citric acid cycle can

neg: ATP citrate lyase The product, acetyl-CoA, in animals serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis. It is activated by insulin. In plants, ATP citrate lyase generates the acetyl-CoA for cytosolically-synthesized metabolites. (Acetyl-CoA is not transported across subcellular membranes of plants.) These include: elongated fatty acids (used in seed oils, membrane phospholipids, the ceramide moiety of sphingolipids, cuticle, cutin, and suberin); flavonoids; malonic acid; acetylated phenolics, alkaloids, isoprenoids, anthocyanins, and sugars; and, mevalonate-derived isoprenoids (e.g., sesquiterpenes, sterols, brassinosteroids); malonyl and acyl-derivatives (d-amino acids, malonylated flavonoids, acylated, prenylated and malonated proteins). De novo fatty acid biosynthesis in plants is plastidic, thus ATP citrate

neg: Acetyl-CoA carboxylase of acetyl CoA. The function of ACC is to regulate the metabolism of fatty acids. When the enzyme is active, the product, malonyl-CoA, is produced which is a building block for new fatty acids and can inhibit the transfer of the fatty acyl group from acyl CoA to carnitine with carnitine acyltransferase, which inhibits the beta-oxidation of fatty acids in the mitochondria. In mammals, two main isoforms of ACC are expressed, ACC1 and ACC2, which differ in both tissue distribution and function. ACC1 is found in the cytoplasm of all cells but is enriched in lipogenic tissue, such as adipose

neg: Acyl CoA dehydrogenase be categorized into three distinct groups based on their specificity for short-, medium-, or long-chain fatty acid acyl-CoA substrates. While different dehydrogenases target fatty acids of varying chain length, all types of ACADs are mechanistically similar. Differences in the enzyme occur based on the location of the active site along the amino acid sequence. ACADs are an important class of enzymes in mammalian cells because of their role in metabolizing fatty acids present in ingested food materials. This enzyme's action represents the first step in fatty acid metabolism (the process of breaking long chains of fatty acids into acetyl CoA

neg: Malonyl-CoA Malonyl-CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. In the former, it provides 2-carbon units to fatty acids and commits them to fatty acid chain synthesis. Malonyl-CoA is formed by carboxylating acetyl-CoA using the enzyme acetyl-CoA carboxylase. One molecule of acetyl-CoA joins with a molecule of bicarbonate, requiring energy rendered from ATP. Malonyl-CoA is utilised in fatty acid biosynthesis by the enzyme malonyl coenzyme A:acyl carrier protein transacylase (MCAT). MCAT serves to transfer malonate from malonyl-CoA to the terminal thiol of "holo"-acyl carrier

neg: Beta oxidation until the entire chain is cleaved into acetyl CoA units. The final cycle produces two separate acetyl CoAs, instead of one acyl CoA and one acetyl CoA. For every cycle, the Acyl CoA unit is shortened by two carbon atoms. Concomitantly, one molecule of FADH, NADH and acetyl CoA are formed. In general, fatty acids with an odd number of carbons are found in the lipids of plants and some marine organisms. Many ruminant animals form a large amount of 3-carbon propionate during the fermentation of carbohydrates in the rumen. Long-chain fatty acids with an odd number of carbon atoms

neg: Natural product other polyketides. The polyketide class of natural products have diverse structures and functions and include prostaglandins and macrolide antibiotics. One molecule of acetyl-CoA (the "starter unit") and several molecules malonyl-CoA (the "extender units") are condensed by fatty acid synthase to produce fatty acids. Fatty acid are essential components of lipid bilayers that form cell membranes as well as fat energy stores in animals. Natural products may be extracted from the cells, tissues, and secretions of microorganisms, plants and animals. A crude (unfractionated) extract from any one of these sources will contain a range of structurally diverse and often novel chemical

neg: Fatty acid degradation Fatty acid degradation Fatty acid degradation is the process in which fatty acids are broken down into their metabolites, in the end generating acetyl-CoA, the entry molecule for the citric acid cycle, the main energy supply of animals. It includes three major steps: Initially in the process of degradation, fatty acids are stored in fat cells (adipocytes). The breakdown of this fat is known as lipolysis. The products of lipolysis, free fatty acids, are released into the bloodstream and circulate throughout the body. During the breakdown of triacylglycerols into fatty acids, more than 75% of the fatty acids are converted

neg: Fatty acid degradation fatty acids, the reaction continues. Once inside the mitochondria, the β-oxidation of fatty acids occurs via five recurring steps: Fatty acid degradation Fatty acid degradation is the process in which fatty acids are broken down into their metabolites, in the end generating acetyl-CoA, the entry molecule for the citric acid cycle, the main energy supply of animals. It includes three major steps: Initially in the process of degradation, fatty acids are stored in fat cells (adipocytes). The breakdown of this fat is known as lipolysis. The products of lipolysis, free fatty acids, are released into the bloodstream and circulate throughout

neg: Fatty acid metabolism is destined to feed into the fatty acid synthesis pathway. Acetyl-CoA carboxylase is the point of regulation in saturated straight-chain fatty acid synthesis, and is subject to both phosphorylation and allosteric regulation. Regulation by phosphorylation occurs mostly in mammals, while allosteric regulation occurs in most organisms. Allosteric control occurs as feedback inhibition by palmitoyl-CoA and activation by citrate. When there are high levels of palmitoyl-CoA, the final product of saturated fatty acid synthesis, it allosterically inactivates acetyl-CoA carboxylase to prevent a build-up of fatty acids in cells. Citrate acts to activate acetyl-CoA carboxylase under high levels, because high levels indicate

neg: Fatty acid always bound to a transport protein, such as albumin. Fatty acids are usually produced industrially by the hydrolysis of triglycerides, with the removal of glycerol (see oleochemicals). Phospholipids represent another source. Some fatty acids are produced synthetically by hydrocarboxylation of alkenes. In animals, fatty acids are formed from carbohydrates predominantly in the liver, adipose tissue, and the mammary glands during lactation. Carbohydrates are converted into pyruvate by glycolysis as the first important step in the conversion of carbohydrates into fatty acids. Pyruvate is then decarboxylated to form acetyl-CoA in the mitochondrion. However, this acetyl CoA needs to be transported into

neg: Lipogenesis Lipogenesis Lipogenesis is the process by which acetyl-CoA is converted to triglycerides (i.e., fat). Acetyl-CoA is an organic compound mainly used to transfer to other compounds the energy obtained by the breakdown of nutrients such as carbohydrates, fatty acids, and ethanol. Through the citric acid cycle, Acetyl-CoA is typically broken down to produce ATP, which is then consumed as a source of energy for many metabolic processes needed for survival or reproduction, such as protein synthesis or muscle contraction. Through lipogenesis, the energy contained in Acetyl-CoA can be efficiently stored for a long time in the form of fats, whenever

neg: Fatty acid metabolism their extensive membranes from glucose, as blood-born fatty acids cannot cross the blood brain barrier to reach these cells. However, how the essential fatty acids, which mammals cannot synthesize themselves, but are nevertheless important components of cell membranes (and other functions described above) reach them is unknown. The pyruvate produced by glycolysis is an important intermediary in the conversion of carbohydrates into fatty acids and cholesterol. This occurs via the conversion of pyruvate into acetyl-CoA in the mitochondrion. However, this acetyl CoA needs to be transported into cytosol where the synthesis of fatty acids and cholesterol occurs. This cannot occur

neg: Acetyl-CoA particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol). CoA is acetylated to acetyl-CoA by the breakdown of carbohydrates through glycolysis and by the breakdown of fatty acids through β-oxidation. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and water, and the energy released captured in the form of 11 ATP and one GTP per acetyl group. Konrad Bloch and Feodor Lynen were awarded the 1964 Nobel Prize in Physiology and Medicine for their discoveries linking acetyl-CoA and fatty acid metabolism. Fritz Lipmann won the Nobel Prize in 1953 for

neg: Fatty acid synthesis cells. Citrate acts to activate acetyl-CoA carboxylase under high levels, because high levels indicate that there is enough acetyl-CoA to feed into the Krebs cycle and conserve energy. High plasma levels of insulin in the blood plasma (e.g. after meals) cause the dephosphorylation of acetyl-CoA carboxylase, thus promoting the formation of malonyl-CoA from acetyl-CoA, and consequently the conversion of carbohydrates into fatty acids, while epinephrine and glucagon (released into the blood during starvation and exercise) cause the phosphorylation of this enzyme, inhibiting lipogenesis in favor of fatty acid oxidation via beta-oxidation. Many bacteria use the anaerobic pathway for synthesizing unsaturated

neg: Adenosine triphosphate between the regulation of the citric acid cycle and glycolysis. In the presence of air and various cofactors and enzymes, fatty acids are converted to acetyl-CoA. The pathway is called beta-oxidation. Each cycle of beta-oxidation shortens the fatty acid chain by two carbon atoms and produces one equivalent each of acetyl-CoA, NADH, and FADH. The acetyl-CoA is metabolized by the citric acid cycle to generate ATP, while the NADH and FADH are used by oxidative phosphorylation to generate ATP. Dozens of ATP equivalents are generated by the beta-oxidation of a single long acyl chain. In oxidative phosphorylation, the key control

neg: Chloroplast of the lipid is from acetyl-CoA, which is the decarboxylation product of pyruvate. Pyruvate may enter the plastid from the cytosol by passive diffusion through the membrane after production in glycolysis. Pyruvate is also made in the plastid from phosphoenolpyruvate, a metabolite made in the cytosol from pyruvate or PGA. Acetate in the cytosol is unavailable for lipid biosynthesis in the plastid. The typical length of fatty acids produced in the plastid are 16 or 18 carbons, with 0-3 cis double bonds. The biosynthesis of fatty acids from acetyl-CoA primarily requires two enzymes. Acetyl-CoA carboxylase creates malonyl-CoA, used in both

neg: Malonyl-CoA decarboxylase length DFAs). While long and medium chain fatty acids are oxidized mainly in the mitochondria, DFAs are oxidized primarily in peroxisomes, which degrade DFAs completely to malonyl-CoA (in the case of odd chain length DFAs) and oxalyl-CoA (for even chain length DFAs). The peroxisomal form of MCD could function to eliminate this final malonyl-CoA. Malonyl-CoA acts as an intermediary between fatty acids and acetyl-CoA in the mitochondria, where MCD is believed to participate in the elimination of the residual malonyl-CoA, so that acetyl-CoA can enter the Krebs cycle. MCD also plays a role in the regulation of glucose and lipids

neg: Ketosis coenzyme A is bound to the fatty acid to produce acyl-CoA, which is able to enter the mitochondria. Once inside the mitochondrion, the dominant way that the bound fatty acids are used as fuel in cells is through β-oxidation, which cleaves two carbons off of the acyl-CoA molecule in every cycle to form acetyl-CoA. Acetyl-CoA enters the citric acid cycle, where it undergoes an aldol condensation with oxaloacetate to form citric acid; citric acid then enters the tricarboxylic acid cycle (TCA), which harvests a very high energy yield per carbon in the original fatty acid. Acetyl-CoA can be metabolized through

neg: Ketogenesis ketolysis. The result is that the liver only produces ketone bodies, but does not use a significant amount of them. Ketogenesis may or may not occur, depending on levels of available carbohydrates in the cell or body. This is closely related to the paths of acetyl-CoA: Insulin and glucagon are key regulating hormones of ketogenesis. Both hormones regulate hormone-sensitive lipase and acetyl-CoA carboxylase. Hormone-sensitive lipase produces diglycerides from triglycerides, freeing a fatty acid molecule for oxidation. Acetyl-CoA carboxylase catalyzes the production of malonyl-CoA from acetyl-CoA. Malonyl-CoA reduces the activity of carnitine palmitoyltransferase I, an enzyme that brings fatty acids into

neg: Fatty acid metabolism that there is enough acetyl-CoA to feed into the Krebs cycle and produce energy. High plasma levels of insulin in the blood plasma (e.g. after meals) cause the dephosphorylation and activation of acetyl-CoA carboxylase, thus promoting the formation of malonyl-CoA from acetyl-CoA, and consequently the conversion of carbohydrates into fatty acids, while epinephrine and glucagon (released into the blood during starvation and exercise) cause the phosphorylation of this enzyme, inhibiting lipogenesis in favor of fatty acid oxidation via beta-oxidation. Disorders of fatty acid metabolism can be described in terms of, for example, hypertriglyceridemia (too high level of triglycerides), or other

neg: Lipid of a lipid, are a diverse group of molecules synthesized by chain-elongation of an acetyl-CoA primer with malonyl-CoA or methylmalonyl-CoA groups in a process called fatty acid synthesis. They are made of a hydrocarbon chain that terminates with a carboxylic acid group; this arrangement confers the molecule with a polar, hydrophilic end, and a nonpolar, hydrophobic end that is insoluble in water. The fatty acid structure is one of the most fundamental categories of biological lipids, and is commonly used as a building-block of more structurally complex lipids. The carbon chain, typically between four and 24 carbons long, may be

neg: Acetyl—CoA synthetase own ethanol, and process (by transesterification) the fatty acid further to create stable fatty acid ethyl esters (FAEEs). Removing the need for further processing prior to obtaining a usable fuel product in Diesel engines. formula_3 "Acetyl CoA used in the production of both ethanol and fatty acids" formula_4 formula_5 Preliminary studies have been conducted where the combination of these two methods have resulted in the production of FAEEs, using acetate as the only carbon source using a combination of the methods described above. It should be noted that the levels of production of all methods mentioned are not up to

neg: Citric acid cycle according to the following reaction scheme: The product of this reaction, acetyl-CoA, is the starting point for the citric acid cycle. Acetyl-CoA may also be obtained from the oxidation of fatty acids. Below is a schematic outline of the cycle: Two carbon atoms are oxidized to CO, the energy from these reactions is transferred to other metabolic processes through GTP (or ATP), and as electrons in NADH and QH. The NADH generated in the citric acid cycle may later be oxidized (donate its electrons) to drive ATP synthesis in a type of process called oxidative phosphorylation. FADH is covalently attached

neg: Gluconeogenesis for isocitrate lyase are found only in nematodes, in which, it is apparent, they originated in horizontal gene transfer from bacteria. The existence of glyoxylate cycles in humans has not been established, and it is widely held that fatty acids cannot be converted to glucose in humans directly. However, carbon-14 has been shown to end up in glucose when it is supplied in fatty acids. Despite these findings, it is considered unlikely that the 2-carbon acetyl-CoA derived from the oxidation of fatty acids would produce a net yield of glucose via the citric acid cycle – however, acetyl-CoA can be

neg: ATP citrate lyase ATP citrate lyase ATP citrate lyase is an enzyme that in animals represents an important step in fatty acid biosynthesis. ATP citrate lyase is important in that, by converting citrate to acetyl CoA, it links the metabolism of carbohydrates, which yields citrate as an intermediate, and the production of fatty acids, which requires acetyl CoA. In plants, ATP citrate lyase generates cytosolic acetyl-CoA precursor of thousands of specialized metabolites including waxes, sterols, and polyketides. ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer of apparently identical subunits.

neg: AMP-activated protein kinase acetyl-CoA to malonyl-CoA, an inhibitor of carnitine palmitoyltransferase 1 (CPT-1). CPT-1 transports fatty acids into the mitochondria for oxidation. Inactivation of ACC, therefore, results in increased fatty acid transport and subsequent oxidation. It is also thought that the decrease in malonyl-CoA occurs as a result of malonyl-CoA decarboxylase (MCD), which may be regulated by AMPK. MCD is an antagonist to ACC, decarboxylating malonyl-CoA to acetyl-CoA, resulting in decreased malonyl-CoA and increased CPT-1 and fatty acid oxidation. AMPK also plays an important role in lipid metabolism in the liver. It has long been known that hepatic ACC has been regulated in

neg: Fatty acid metabolism and the substrates that are used. The two pathways are mutually inhibitory, preventing the acetyl-CoA produced by beta-oxidation from entering the synthetic pathway via the acetyl-CoA carboxylase reaction. It can also not be converted to pyruvate as the pyruvate dehydrogenase complex reaction is irreversible. Instead the acetyl-CoA produced by the beta-oxidation of fatty acids condenses with oxaloacetate, to enter the citric acid cycle. During each turn of the cycle, two carbon atoms leave the cycle as CO in the decarboxylation reactions catalyzed by isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase. Thus each turn of the citric acid cycle oxidizes an acetyl-CoA unit

neg: Fatty acid degradation activated, the acyl CoA is transported into the mitochondrial matrix. This occurs via a series of similar steps: It is important to note that "carnitine acyltransferase I" undergoes allosteric inhibition as a result of malonyl-CoA, an intermediate in fatty acid biosynthesis, in order to prevent futile cycling between beta-oxidation and fatty acid synthesis. The mitochondrial oxidation of fatty acids takes place in three major steps: 1.β-oxidation: conversion of fatty acids into 2-carbon acetyl Co-A units. 2.entry of acetyl Co-A into TCA cycle to yield energy. 3.finally, the electron transport chain in the mitochondria.though in this step, no direct participation of

neg: Ketone bodies Ketone bodies Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) containing the ketone group that are produced by the liver from fatty acids during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise, alcoholism or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues (tissues outside the liver) and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy. In the brain, ketone bodies are also used to make acetyl-CoA into

neg: Citric acid acetyl-CoA into malonyl-CoA (the commitment step in fatty acid synthesis). In short, citrate is transported to the cytoplasm, converted to acetyl CoA, which is converted into malonyl CoA by the acetyl CoA carboxylase, which is allosterically modulated by citrate. High concentrations of cytosolic citrate can inhibit phosphofructokinase, the catalyst of one of the rate-limiting steps of glycolysis. This effect is advantageous: high concentrations of citrate indicate that there is a large supply of biosynthetic precursor molecules, so there is no need for phosphofructokinase to continue to send molecules of its substrate, fructose 6-phosphate, into glycolysis. Citrate acts by augmenting the

neg: Ketogenesis the mitochondria for β-oxidation. Insulin inhibits hormone-sensitive lipase and activates acetyl-CoA carboxylase, thereby reducing the amount of starting materials for fatty acid oxidation and inhibiting their capacity to enter the mitochondria. Glucagon activates hormone-sensitive lipase and inhibits acetyl-CoA carboxylase, thereby stimulating ketone body production, and making passage into the mitochondria for β-oxidation easier. Insulin also inhibits HMG-CoA lyase, further inhibiting ketone body production. Similarly, cortisol, catecholamines, epinephrine, norepinephrine, and thyroid hormones can increase the amount of ketone bodies produced, by activating lipolysis (the mobilization of fatty acids out of fat tissue) and thereby increasing the concentration of fatty acids available

neg: Citric acid cycle cytosol. There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to mitochondrion as "malate" (and then converted back into "oxaloacetate" to transfer more "acetyl-CoA" out of the mitochondrion). The cytosolic acetyl-CoA is used for fatty acid synthesis and the production of cholesterol. Cholesterol can, in turn, be used to synthesize the steroid hormones, bile salts, and vitamin D. The carbon skeletons of many non-essential amino acids are made from citric acid cycle intermediates. To turn them into amino acids the alpha keto-acids formed from the citric acid cycle intermediates have to acquire their

neg: Lipogenesis an antagonistic effect and increases phosphorylation, deactivation, thereby inhibiting ACC and slowing fat synthesis. Affecting ACC affects the rate of acetyl-CoA conversion to malonyl-CoA. Increased malonyl-CoA level pushes the equilibrium over to increase production of fatty acids through biosynthesis. Long chain fatty acids are negative allosteric regulators of ACC and so when the cell has sufficient long chain fatty acids, they will eventually inhibit ACC activity and stop fatty acid synthesis. AMP and ATP concentrations of the cell act as a measure of the ATP needs of a cell. When ATP is depleted, there is a rise in 5'AMP. This

neg: Fatty acid synthesis There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate can be used for gluconeogenesis (in the liver), or it can be returned into mitochondrion as malate. The cytosolic acetyl-CoA is carboxylated by acetyl CoA carboxylase into malonyl CoA, the first committed step in the synthesis of fatty acids. The main fuel stored in the bodies of animals is fat. The young adult human's fat stores average between about 10–20 kg, but varies greatly depending on age, gender, and individual disposition. By contrast the human body stores only about 400 g of glycogen, of which 300

neg: Methylmalonyl-CoA mutase deficiency described for propanoyl-CoA. Odd chain fatty acids are also metabolized through the methylmalonyl pathway. The degradation of odd chain fatty acids releases Acetyl-CoA and propionyl-CoA. Propionyl-CoA is then converted to succinyl-CoA, and both succinyl-CoA and propionyl-CoA are interjected into the tricarboxylic acid cycle for continued production of reductant. The final product of methylmalonyl-CoA mutase activity is succinyl-CoA which is a tricarboxylic acid cycle substrate. A side effect of excess methylmalonyl-CoA is an interruption of the enzymes responsible for other transformations earlier in the metabolism of propionyl-CoA, leading to propanoic acidemia as well. This, along with an excess of methylmalonyl-CoA leads

neg: Fatty acid synthesis a 16:0 carbon fatty acid has been formed, it can undergo a number of modifications, resulting in desaturation and/or elongation. Elongation, starting with stearate (18:0), is performed mainly in the ER by several membrane-bound enzymes. The enzymatic steps involved in the elongation process are principally the same as those carried out by FAS, but the four principal successive steps of the elongation are performed by individual proteins, which may be physically associated. Note that during fatty synthesis the reducing agent is NADPH, whereas NAD is the oxidizing agent in beta-oxidation (the breakdown of fatty acids to acetyl-CoA). This difference exemplifies

neg: Methylmalonyl CoA epimerase reactions to yield one acetyl CoA per repeated sequence. This means that, for each round of β-oxidation, the fatty acyl-Co-A is shortened by two carbons. If the fatty acid began with an even number of carbons, this process could break down an entire saturated fatty acid into acetyl-CoA units. If the fatty acid began with an odd number of carbons, however, β-oxidation would break the fatty acyl-CoA down until the three carbon propionyl-CoA is formed. In order to convert this to the metabolically useful succinyl-CoA, three reactions are needed. The propionyl-CoA is first carboxylated to ("S")-methylmalonyl-CoA by the enzyme Propionyl-CoA

neg: Acetyl-CoA carboxylase Acetyl-CoA carboxylase Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is a multi-subunit enzyme in most prokaryotes and in the chloroplasts of most plants and algae, whereas it is a large, multi-domain enzyme in the endoplasmic reticulum of most eukaryotes. The most important function of ACC is to provide the malonyl-CoA substrate for the biosynthesis of fatty acids. The activity of ACC can be controlled at the transcriptional level as well as by small molecule modulators and covalent modification.

neg: Propionyl-CoA carboxylase Propionyl-CoA carboxylase Propionyl-CoA carboxylase (PCC) catalyses the carboxylation reaction of propionyl CoA in the mitochondrial matrix. The enzyme is biotin-dependent. The product of the reaction is (S)-methylmalonyl CoA. Propionyl CoA is the end product of metabolism of odd-chain fatty acids, and is also a metabolite of most methyl-branched fatty acids. It is also the main metabolite of valine, and together with acetyl-CoA, is a metabolite of isoleucine, as well as a methionine metabolite. Propionyl-CoA is thus of great importance as a glucose precursor. (S)-Methylmalonyl-CoA is not directly utilizable by animals; it is acted on by a racemase to give (R)-methylmalonyl-CoA.

neg: Fatty acyl-CoA esters shuttle mechanism is required only for longer chain fatty acids. Once inside the mitochondrial matrix, the fatty acyl-CoA derivatives are degraded by a series of reactions that release acetyl-CoA and leads to the production of NADH and FADH2. There are four steps in fatty acid oxidation pathway; oxidation, hydration, oxidation, and thiolysis. It requires 7 rounds of this pathway to degrade palmitate (a C16 fatty acid). Fatty acyl-CoA esters Fatty acyl-CoA esters are fatty acid derivatives formed of one fatty acid, a 3'-phospho-AMP linked to phosphorylated pantothenic acid (Vitamin B) and cysteamine. Long-chain acyl-CoA esters are substrates for a number

neg: Fatty acid synthesis each turn of the citric acid cycle oxidizes an acetyl-CoA unit while regenerating the oxaloacetate molecule with which the acetyl-CoA had originally combined to form citric acid. The decarboxylation reactions occur before malate is formed in the cycle. This is the only substance that can be removed from the mitochondrion to enter the gluconeogenic pathway to form glucose or glycogen in the liver or any other tissue. There can therefore be no net conversion of fatty acids into glucose. Only plants possess the enzymes to convert acetyl-CoA into oxaloacetate from which malate can be formed to ultimately be converted to

neg: Fatty acid metabolism carried out by FAS, but the four principal successive steps of the elongation are performed by individual proteins, which may be physically associated. Abbreviations: ACP – Acyl carrier protein, CoA – Coenzyme A, NADP – Nicotinamide adenine dinucleotide phosphate. Note that during fatty synthesis the reducing agent is NADPH, whereas NAD is the oxidizing agent in beta-oxidation (the breakdown of fatty acids to acetyl-CoA). This difference exemplifies a general principle that NADPH is consumed during biosynthetic reactions, whereas NADH is generated in energy-yielding reactions. (Thus NADPH is also required for the synthesis of cholesterol from acetyl-CoA; while NADH is generated

neg: Ketone bodies long-chain fatty acids. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids). They are therefore always released into the blood by the liver together with newly produced glucose after the liver glycogen stores have been depleted (these glycogen stores are depleted within the first 24 hours of fasting). When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent)

neg: Acetylcarnitine leaving free CoA inside the mitochondria ready to accept new import of fatty acid chains. ALCAR in the cytosol can also form a pool of acetyl-groups for CoA, should the cell need it. Excess acetyl-CoA causes more carbohydrates to be used for energy at the expense of fatty acids. This occurs by different mechanisms inside and outside the mitochondria. ALCAR transport decreases acetyl-CoA inside the mitochondria, but increases it outside. Carnitine and ALCAR supplements carry warnings of a risk that they promote seizures in people with epilepsy, but a 2016 review found no basis for this warning in the literature.

neg: Ketosis thiolase. Acetoacetyl-CoA momentarily combines with another acetyl-CoA via HMG-CoA synthase to form hydroxy-β-methylglutaryl-CoA. Hydroxy-β-methylglutaryl-CoA form the ketone body acetoacetate via HMG-CoA lyase. Acetoacetate can then reversibly convert to another ketone body—D-β-hydroxybutyrate—via D-β-hydroxybutyrate dehydrogenase. Alternatively, acetoacetate can spontaneously degrade to a third ketone body (acetone) and carbon dioxide, although the process generates much greater concentrations of acetoacetate and D-β-hydroxybutyrate. When blood glucose levels are low, ketone bodies can be exported from the liver to supply crucial energy to the brain. Along with the fatty acids, deaminated ketogenic amino acids can also be converted into intermediates in the citric acid cycle and

neg: Coenzyme A Coenzyme A Co-enzyme A (CoA,SCoA,CoASH) is a co-enzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester, such as acetyl-CoA) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenate, and adenosine triphosphate (ATP). Acetyl -CoA In it's acetyl form, Coenzyme A is a very versatile molecule in metabolism because it functions in anabolic and catabolic pathways. The acetyl CoA uses post-translational

neg: ACOT4 have a unique purpose in that they generate the free acid and CoA, as opposed to long-chain acyl-CoA synthetases, which ligate fatty acids to CoA, to produce the CoA ester. The role of the ACOT- family of enzymes is not well understood; however, it has been suggested that they play a crucial role in regulating the intracellular levels of CoA esters, Coenzyme A, and free fatty acids. Recent studies have shown that Acyl-CoA esters have many more functions than simply an energy source. These functions include allosteric regulation of enzymes such as acetyl-CoA carboxylase, hexokinase IV, and the citrate condensing

neg: Malate synthase skip over the decarboxylation steps of the citric acid cycle. In other words, malate synthase works together with isocitrate lyase in the glyoxylate cycle to bypass two oxidative steps of Krebs cycle and permit carbon incorporation from acetate or fatty acids in many microorganisms. Together, these two enzymes serve to produce succinate (which exits the cycle to be used for synthesis of sugars) and malate (which remains in the glyoxylate cycle). During this process, acetyl-CoA and water are used as substrates. As a result, the cell does not lose 2 molecules of carbon dioxide as it does in the Krebs

neg: Coenzyme A A is, in chemical terms, a thiol, it can react with carboxylic acids to form thioesters, thus functioning as an acyl group carrier. It assists in transferring fatty acids from the cytoplasm to mitochondria. A molecule of coenzyme A carrying an acetyl group is also referred to as acyl-CoA. When it is not attached to an acyl group, it is usually referred to as 'CoASH' or 'HSCoA'. This process facilitates the production of fatty acids in cells, which are essential in cell membrane structure. Coenzyme A is also the source of the phosphopantetheine group that is added as a prosthetic

neg: Fatty acid synthase Fatty acid synthase Fatty acid synthase (FAS) is an enzyme that in humans is encoded by the "FASN" gene. Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis. It is not a single enzyme but a whole enzymatic system composed of two identical 272 kDa multifunctional polypeptides, in which substrates are handed from one functional domain to the next. Its main function is to catalyze the synthesis of palmitate (C16:0, a long-chain saturated fatty acid) from acetyl-CoA and malonyl-CoA, in the presence of NADPH. Fatty acids are aliphatic acids fundamental to energy production and storage, cellular structure

neg: Ketogenesis they are not as effective at doing so. Ketogenesis occurs constantly in a healthy individual. Ketogenesis takes place in the setting of low glucose levels in the blood, after exhaustion of other cellular carbohydrate stores, such as glycogen. It can also take place when there is insufficient insulin (e.g. in type 1 (but not 2) diabetes), particularly during periods of "ketogenic stress" such as intercurrent illness. The production of ketone bodies is then initiated to make available energy that is stored as fatty acids. Fatty acids are enzymatically broken down in β-oxidation to form acetyl-CoA. Under normal conditions, acetyl-CoA is

neg: Beta oxidation of the tissues in the body. However, some tissues such as the red blood cells of mammals (which do not contain mitochondria), and cells of the central nervous system do not use fatty acids for their energy requirements, but instead use carbohydrates (red blood cells and neurons) or ketone bodies (neurons only). Because many fatty acids are not fully saturated or do not have an even number of carbons, several different mechanisms have evolved, described below. Once inside the mitochondria, each cycle of β-oxidation, liberating a two carbon unit (acetyl-CoA), occurs in a sequence of four reactions: This process continues

neg: Glycogen storage disease type I adult body for 12–18 hours. When fasting continues for more than a few hours, falling insulin levels permit catabolism of muscle protein and triglycerides from adipose tissue. The products of these processes are amino acids (mainly alanine), free fatty acids, and lactic acid. Free fatty acids from triglycerides are converted to ketones, and to acetyl-CoA. Amino acids and lactic acid are used to synthesize new G6P in liver cells by the process of gluconeogenesis. The last step of normal gluconeogenesis, like the last step of glycogenolysis, is the dephosphorylation of G6P by glucose-6-phosphatase to free glucose and . Thus glucose-6-phosphatase

neg: Acetyl—CoA synthetase coli to use acetate as a feedstock, these microbes were able to survive and produce their engineered products. These fatty acids could then be used as a biofuel after being separated from the media, requiring further processing (transesterification) to yield usable biodiesel fuel. Original adaptation protocol for inducing high levels of acetate uptake was innovated in 1959 as a means to induce starvation mechanisms in "E. coli". formula_1 formula_2 Acetyl-CoA from the breakdown of sugars in glycolysis have been sued to build fatty acids. However the difference comes in the fact that the Keasling strain is able to synthesize its

neg: Randle cycle palmitoyltransferase (CPT) that controls the entry and oxidation of LCFA. The glucose-derived malonyl-CoA prevents the oxidation of fatty acids and favors fatty acid esterification. The concentration of malonyl-CoA depends on the balance between acetyl-CoA carboxylase (ACC) and malonyl-CoA decarboxylase (MCD). AMP-activated protein kinase (AMPK) is reported to phosphorylate and inactivate liver ACC. This in turn decreases malonyl-CoA concentrations which stimulates fatty acid oxidation and ketogenesis by glucagon in the liver. AMPK phosphorylates and inactivates ACC in the liver and other tissues. Inhibition of fatty acid oxidation requires that ACC is active. Both AMPK and MCD are inactive and glucose uptake

neg: Methylmalonyl CoA epimerase The structure of the MCEE protein has been resolved by X-ray crystallography at 1.8-angstrom resolution. The MCEE gene encodes an enzyme that interconverts D- and L- methylmalonyl-CoA during the degradation of branched-chain amino acids, odd chain-length fatty acids, and other metabolites. In biochemistry terms, it catalyzes the reaction that converts ("S")-methylmalonyl-CoA to the ("R") form. This enzyme catalyses the following chemical reaction Methylmalonyl CoA epimerase plays an important role in the catabolism of fatty acids with odd-length carbon chains. In the catabolism of even-chain saturated fatty acids, the β-oxidation pathway breaks down fatty acyl-CoA molecules in repeated sequences of four

neg: 6-Deoxyerythronolide B synthase or Acyl Carrier Protein. However, in fatty acid synthesis the original molecules are Acyl-CoA or Malonyl-CoA but poyketide synthases can use multiple primers including Acetyl-CoA, Propionyl-CoA, Isobutyrl-CoA, Cyclohexanoyl-CoA, 3-amino-5-hydroxybenzoyl-CoA, or Cinnamyl-CoA. In both fatty acid synthesis and polyketide synthesis these CoA carriers will be exchanged for ACP before they are incorporated into the growing molecule. During the elongation steps of fatty acid synthesis, ketosynthase, ketoreductase, dehydratase, and enoylreductase are all used in sequence to create a saturated fatty acid then postsynthetic modification can be done to create an unsaturated or cyclo fatty acid. However, in polyketide synthesis these enzymes can

neg: Isoleucine involved in this biosynthesis include: Isoleucine is both a glucogenic and a ketogenic amino acid. After transamination with alpha-ketoglutarate the carbon skeleton can be converted into either succinyl CoA, and fed into the TCA cycle for oxidation or converted into oxaloacetate for gluconeogenesis (hence glucogenic). It can also be converted into acetyl CoA and fed into the TCA cycle by condensing with oxaloacetate to form citrate. In mammals Acetyl CoA cannot be converted back to carbohydrate but can be used in the synthesis of ketone bodies or fatty acids, hence ketogenic. Isoleucine, like other branched-chain amino acids, is associated with

neg: Long-chain-fatty-acid—CoA ligase chain fatty acids from entering the peroxisome. Human genes encoding long-chain-fatty-acid—CoA ligase enzymes (also known as acyl-CoA synthetase long-chain, or ACSL) include: Long-chain-fatty-acid—CoA ligase The long chain fatty acyl-CoA ligase (or synthetase) is an enzyme of the ligase family that activates the breakdown of complex fatty acids. Long chain fatty acyl-CoA synthetase catalyzes the formation of fatty acyl-CoA by a two-step process proceeding through an adenylated intermediate. The enzyme catalyzes the following reaction: It is present in all organisms from bacteria to humans. It catalyzes the pre-step reaction for β-oxidation of fatty acids or can be incorporated in phospholipids. Long

neg: ACSF3 ACSF3 Acyl-CoA synthetase family member 3 is an enzyme that in humans is encoded by the ACSF3 gene. The ACSF3 gene is located on the 16th chromosome, with its specific location being 16q24.3. The gene contains 17 exons. ASCL4 encodes a 64.1 kDa protein that is composed of 576 amino acids; 20 peptides have been observed through mass spectrometry data. This gene encodes a member of the acetyl—CoA synthetase family of enzymes that activate fatty acids by catalyzing the formation of a thioester linkage between fatty acids and coenzyme A. The encoded protein is localized to mitochondria, has high specificity

neg: Carbohydrate metabolism from muscle cells. Carbohydrates are typically stored as long polymers of glucose molecules with glycosidic bonds for structural support (e.g. chitin, cellulose) or for energy storage (e.g. glycogen, starch). However, the strong affinity of most carbohydrates for water makes storage of large quantities of carbohydrates inefficient due to the large molecular weight of the solvated water-carbohydrate complex. In most organisms, excess carbohydrates are regularly catabolised to form acetyl-CoA, which is a feed stock for the fatty acid synthesis pathway; fatty acids, triglycerides, and other lipids are commonly used for long-term energy storage. The hydrophobic character of lipids makes them a

neg: Lipid metabolism the conversion of phosphatidic acid to diacylglyceride, which will be converted to triacylglyceride by acyltransferase. Tryglyceride biosynthesis occurs in the cytosol. The precursor for fatty acids is acetyl coA and it occurs in the cytosol of the cell. The overall net reaction, using palmitate (16:0) as a model substrate is: 8 Acetyl-coA + 7 ATP + 14 NADPH + 6H+ → palmitate + 14 NADP+ + 6H2O + 7ADP + 7P¡ Cholesterol can be made from acetyl-CoA through a multiple-step pathway known as Isoprenoid Pathway. Cholesterols are essential because they can be modified to form different hormones in the body

neg: ACACB ACACB Acetyl-CoA carboxylase 2 also known as ACC-beta or ACC2 is an enzyme that in humans is encoded by the "ACACB" gene. Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine palmitoyltransferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. Human acetyl-CoA

neg: Oxaloacetic acid The acetyl-CoA is transported as a citrate, which has been previously formed in the mitochondrial matrix from acetyl-coA and oxaloacetate. This reaction usually initiates the citric acid cycle, but when there is no need of energy it is transported to the cytoplasm where it is broken down to cytoplasmatic acetyl -CoA and oxaloacetate. Another part of the cycle requires NADPH for the synthesis of fatty acids. Part of this reducing power is generated when the cytosolic oxaloacetate is returned to the mitochondria as long as the internal mitochondrial layer is non-permeable for oxaloacetate. Firstly the oxaloacetate is reduced to malate

neg: Citric acid cycle rate of ATP production by the mitochondrion, and thus the availability of ATP to the cell. "Acetyl-CoA", on the other hand, derived from pyruvate oxidation, or from the beta-oxidation of fatty acids, is the only fuel to enter the citric acid cycle. With each turn of the cycle one molecule of "acetyl-CoA" is consumed for every molecule of "oxaloacetate" present in the mitochondrial matrix, and is never regenerated. It is the oxidation of the acetate portion of "acetyl-CoA" that produces CO and water, with the energy thus released captured in the form of ATP. The three steps of beta-oxidation resemble

neg: Acetyl—CoA synthetase acetyl-CoA to histone acetyltransferases for histone acetylation. Without correct acetylation, DNA cannot condense into chromatin properly, which inevitably results in transcriptional errors. By taking advantage of the pathways which use acetyl-CoA as a substrate, engineered products can be obtained which have potential to be consumer products. By overexpressing the acs gene, and using acetate as a feedstock, the production of fatty acids (FAs) may be increased. The use of acetate as a feed stock is uncommon, as acetate is a normal waste product of "E. coli" metabolism and is toxic at high levels to the organism. By adapting the E.

neg: Acyl-CoA form an acyl-CoA. The acyladenylate product of the first step has a large free energy of hydrolysis and conserves the free energy of the cleaved phosphoanhydride bond in ATP. The second step, transfer of the acyl group to CoA (the same molecule that carries acetyl groups as acetyl-CoA), conserves free energy in the formation of a thioester bond. Consequently, the overall reaction has a free energy change near zero: Subsequent hydrolysis of the product PP (by the enzyme inorganic pyrophosphatase) is highly exergonic, and this reaction makes the formation of acyl-CoA spontaneous and irreversible. Fatty acids are activated in the