text:
Fatty acid metabolism
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Fatty acid metabolism consists of catabolic processes that generate energy, and anabolic processes that create biologically important molecules (triglycerides, phospholipids, second messengers, local hormones and ketone bodies).[1] Fatty acids are a family of molecules classified within the lipid macronutrient class. One role of fatty acids in animal metabolism is energy production, captured in the form of adenosine triphosphate (ATP). When compared to other macronutrient classes (carbohydrates and protein), fatty acids yield the most ATP on an energy per gram basis, when they are completely oxidized to CO2 and water by beta oxidation and the citric acid cycle.[2] Fatty acids (mainly in the form of triglycerides) are therefore the foremost storage form of fuel in most animals, and to a lesser extent in plants. In addition, fatty acids are important components of the phospholipids that form the phospholipid bilayers out of which all the membranes of the cell are constructed (the cell wall, and the membranes that enclose all the organelles within the cells, such as the nucleus, the mitochondria, endoplasmic reticulum, and the Golgi apparatus). Fatty acids can also be cleaved, or partially cleaved, from their chemical attachments in the cell membrane to form second messengers within the cell, and local hormones in the immediate vicinity of the cell. The prostaglandins made from arachidonic acid stored in the cell membrane, are probably the most well known group of these local hormones.
Contents
[hide]
1 Fatty acid catabolism
1.1 Fatty acids as an energy source
1.2 Animals and plants synthesize carbohydrates from both glycerol and fatty acids
2 Other functions and uses of fatty acids
2.1 Intracellular signaling
2.2 Eicosanoid paracrine hormones
3 Dietary sources of fatty acids, their digestion, absorption, transport in the blood and storage
4 Fatty acid synthesis
4.1 Glycolytic end products are used in the conversion of carbohydrates into fatty acids
4.2 Regulation of fatty acid synthesis
5 Disorders
6 References
Fatty acid catabolism[edit]
A diagrammatic illustration of the process of lipolysis (in a fat cell) induced by high epinephrine and low insulin levels in the blood. Epinephrine binds to a beta-adrenergic receptor in the cell wall of the adipocyte, which causes cAMP to be generated inside the cell. The cAMP activates a protein kinase, which phosphorylates and thus, in turn, activates a hormone-sensitive lipase in the fat cell. This lipase cleaves free fatty acids from their attachment to glycerol in the fat stored in the fat droplet of the adipocyte. The free fatty acids and glycerol are then released into the blood. However more recent studies have shown that adipose triglyceride lipase has to first convert triacylglycerides to diacylglycerides, and that hormone-sensitive lipase converts the diacylglycerides to monoglycerides and free fatty acids. Monoglycerides are hydrolyzed by monoglyceride lipase.[3] The activity of hormone sensitive lipase is regulated by the circulation hormones insulin, glucagon, norepinephrine, and epinephrine, as shown in the diagram.
A diagrammatic illustration of the transport of free fatty acids in the blood attached to plasma albumin, its diffusion across the cell membrane using a protein transporter, and its activation, using ATP, to form acyl-CoA in the cytosol. The illustration is, for diagrammatic purposes, of a 12 carbon fatty acid. Most fatty acids in human plasma are 16 or 18 carbon atoms long.
A diagrammatic illustration of the transfer of an acyl-CoA molecule across the inner membrane of the mitochondrion by carnitine-acyl-CoA transferase (CAT). The illustrated acyl chain is, for diagrammatic purposes, only 12 carbon atoms long. Most fatty acids in human plasma are 16 or 18 carbon atoms long. CAT is inhibited by high concentrations of malonyl-CoA (the first committed step in fatty acid synthesis) in the cytoplasm. This means that fatty acid synthesis and fatty acid catabolism cannot occur simultaneously in any given cell.
A diagrammatic illustration of the process of the beta-oxidation of an acyl-CoA molecule in the mitochodrial matrix. During this process an acyl-CoA molecule which is 2 carbons shorter than it was at the beginning of the process is formed. Acetyl-CoA, water and 5 ATP molecules are the other products of each beta-oxidative event, until the entire acyl-CoA molecule has been reduced to a set of acetyl-CoA molecules.
Fatty acids are released, between meals, from the fat depots in adipose tissue, where they are stored as triglycerides, as follows:
Lipolysis, the removal of the fatty acid chains from the glycerol to which they are bound in their storage form as triglycerides (or fats), is carried out by lipases. These lipases are activated by high epinephrine and glucagon levels in the blood (or norepinephrine secreted by sympathetic nerves in adipose tissue), caused by declining blood glucose levels after meals, which simultaneously lowers the insulin level in the blood.[1]
Once freed from glycerol, the free fatty acids enter the blood, which transports them, attached to plasma albumin, throughout the body.[4]
Long chain free fatty acids enter the metabolizing cells (i.e. most living cells in the body except red blood cells and neurons in the central nervous system) through specific transport proteins, such as the SLC27 family fatty acid transport protein.[5][6] Red blood cells do not contain mitochondria and are therefore incapable of metabolizing fatty acids; the tissues of the central nervous system cannot use fatty acids, despite containing mitochondria, because long chain fatty acids (as opposed to medium chain fatty acids[7][8]) cannot cross the blood brain barrier[9] into the interstitial fluids that bathe these cells.
Once inside the cell long-chain-fatty-acid—CoA ligase catalyzes the reaction between a fatty acid molecule with ATP (which is broken down to AMP and inorganic pyrophosphate) to give a fatty acyl-adenylate, which then reacts with free coenzyme A to give a fatty acyl-CoA molecule.
In order for the acyl-CoA to enter the mitochondrion the carnitine shuttle is used:[10][11][12]
Acyl-CoA is transferred to the hydroxyl group of carnitine by carnitine palmitoyltransferase I, located on the cytosolic faces of the outer and inner mitochondrial membranes.
Acyl-carnitine is shuttled inside by a carnitine-acylcarnitine translocase, as a carnitine is shuttled outside.
Acyl-carnitine is converted back to acyl-CoA by carnitine palmitoyltransferase II, located on the interior face of the inner mitochondrial membrane. The liberated carnitine is shuttled back to the cytosol, as an acyl-CoA is shuttled into the matrix.
Beta oxidation, in the mitochondrial matrix, then cuts the long carbon chains of the fatty acids (in the form of acyl-CoA molecules) into a series of two-carbon (acetate) units, which, combined with co-enzyme A, form molecules of acetyl CoA, which condense with oxaloacetate to form citrate at the "beginning" of the citric acid cycle.[2] It is convenient to think of this reaction as marking the "starting point" of the cycle, as this is when fuel - acetyl-CoA - is added to the cycle, which will be dissipated as CO2 and H2O with the release of a substantial quantity of energy captured in the form of ATP, during the course of each turn of the cycle.
Briefly, the steps in beta oxidation (the initial breakdown of free fatty acids into acetyl-CoA) are as follows:[2]
Dehydrogenation by acyl-CoA dehydrogenase, yielding 1 FADH2
Hydration by enoyl-CoA hydratase
Dehydrogenation by 3-hydroxyacyl-CoA dehydrogenase, yielding 1 NADH + H+
Cleavage by thiolase, yielding 1 acetyl-CoA and a fatty acid that has now been shortened by 2 carbons (forming a new, shortened acyl-CoA)
This beta oxidation reaction is repeated until the fatty acid has been completely reduced to acetyl-CoA or, in, the case of fatty acids with odd numbers of carbon atoms, acetyl-CoA and 1 molecule of propionyl-CoA per molecule of fatty acid. Each beta oxidative cut of the acyl-CoA molecule yields 5 ATP molecules.[13][14]
The acetyl-CoA produced by beta 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-CoA to CO2 and water. The energy released in this process is captured in the form of 1 GTP and 11 ATP molecules per acetyl-CoA molecule oxidized.[2][10] This is the fate of acetyl-CoA wherever beta oxidation of fatty acids occurs, except under certain circumstances in the liver.
In the liver oxaloacetate can be wholly or partially diverted into the gluconeogenic pathway during fasting, starvation, a low carbohydrate diet, prolonged strenuous exercise, and in uncontrolled type 1 diabetes mellitus. Under these circumstances oxaloacetate is hydrogenated to malate which is then removed from the mitochondrion to be converted into glucose in the cytoplasm of the liver cells, from where it is released into the blood.[10] In the liver, therefore, oxaloacetate is unavailable for condensation with acetyl-CoA when significant gluconeogenesis has been stimulated by low (or absent) insulin and high glucagon concentrations in the blood. Under these circumstances acetyl-CoA is diverted to the formation of acetoacetate and beta-hydroxybutyrate.[10] Acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone, are frequently, but confusingly, known as ketone bodies (as they are not "bodies" at all, but water-soluble chemical substances). The ketone bodies are released by the liver into the blood. All cells with mitochondria can take ketone bodies up from the blood and reconvert them into acetyl-CoA, which can then be used as fuel in their citric acid cycles, as no other tissue can divert its oxaloacetate into the gluconeogenic pathway in the way that this can occur in the liver. Unlike free fatty acids, ketone bodies can cross the blood-brain barrier and are therefore available as fuel for the cells of the central nervous system, acting as a substitute for glucose, on which these cells normally survive.[10] The occurrence of high levels of ketone bodies in the blood during starvation, a low carbohydrate diet, prolonged heavy exercise and uncontrolled type 1 diabetes mellitus is known as ketosis, and, in its extreme form, in out-of-control type 1 diabetes mellitus, as ketoacidosis.
The glycerol released by lipase action is phosphorylated by glycerol kinase in the liver (the only tissue in which this reaction can occur), and the resulting glycerol 3-phosphate is oxidized to dihydroxyacetone phosphate. The glycolytic enzyme triose phosphate isomerase converts this compound to glyceraldehyde 3-phosphate, which is oxidized via glycolysis, or converted to glucose via gluconeogenesis.
Fatty acids as an energy source[edit]
Example of an unsaturated fat triglyceride. Left part: glycerol, right part from top to bottom: palmitic acid, oleic acid, alpha-linolenic acid. Chemical formula: C55H98O6
Fatty acids, stored as triglycerides in an organism, are an important source of energy because they are both reduced and anhydrous. The energy yield from a gram of fatty acids is approximately 9 kcal (37 kJ), compared to 4 kcal (17 kJ) for carbohydrates. Since the hydrocarbon portion of fatty acids is hydrophobic, these molecules can be stored in a relatively anhydrous (water-free) environment. Carbohydrates, on the other hand, are more highly hydrated. For example, 1 g of glycogen can bind approximately 2 g of water, which translates to 1.33 kcal/g (4 kcal/3 g). This means that fatty acids can hold more than six times the amount of energy per unit of storage mass. Put another way, if the human body relied on carbohydrates to store energy, then a person would need to carry 31 kg (67.5 lb) of hydrated glycogen to have the energy equivalent to 4.6 kg (10 lb) of fat.[10]
Hibernating animals provide a good example for utilizing fat reserves as fuel. For example, bears hibernate for about 7 months, and, during this entire period, the energy is derived from degradation of fat stores. Migrating birds similarly build up large fat reserves before embarking on their intercontinental journeys.[15]
Thus the young adult human’s fat stores average between about 10–20 kg, but varies greatly depending on age, gender, and individual disposition.[16] By contrast the human body stores only about 400 g of glycogen, of which 300 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.[10] 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.[1] Please note however that lipolysis releases glycerol which can enter the pathway of gluconeogenesis.
Animals and plants synthesize carbohydrates from both glycerol and fatty acids[edit]
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, 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.[1] It can also not be converted to pyruvate as the pyruvate dehydrogenase complex reaction is irreversible.[10] 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 CO2 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 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.[1] Only plants possess the enzymes to convert acetyl-CoA into oxaloacetate from which malate can be formed to ultimately be converted to glucose.[1]
However acetyl-CoA can be converted to acetoacetate, which can decarboxylate to acetone (either spontaneously, or by acetoacetate decarboxylase). It can then be further metabolized to isopropanol which is excreted in breath/urine, or by CYP2E1 into hydroxyacetone (acetol). Acetol can be converted to propylene glycol. This converts to formate and acetate (the latter converting to glucose), or pyruvate (by two alternative enzymes), or propionaldehyde, or to L-lactaldehyde then L-lactate (the common lactate isomer).[17][18][19] Another pathway turns acetol to methylglyoxal, then to pyruvate, or to D-lactaldehyde (via S-D-lactoyl-glutathione or otherwise) then D-lactate.[18][20][21] D-lactate metabolism (to glucose) is slow or impaired in humans, so most of the D-lactate is excreted in the urine; thus D-lactate derived from acetone can contribute significantly to the metabolic acidosis associated with ketosis or isopropanol intoxication.[18] L-Lactate can complete the net conversion of fatty acids into glucose. The first experiment to show conversion of acetone to glucose was carried out in 1951. This, and further experiments used carbon isotopic labelling.[19] Up to 11% of the glucose can be derived from acetone during starvation in humans.[19]
The glycerol released into the blood during the lipolysis of triglycerides in adipose tissue can only be taken up by the liver. Here it is converted into glycerol 3-phosphate by the action of glycerol kinase which hydrolyzes one molecule of ATP per glycerol molecule which is phosphorylated. Glycerol 3-phosphate is then oxidized to dihydroxyacetone phosphate, which is, in turn, converted into glyceraldehyde 3-phosphate by the enzyme triose phosphate isomerase. From here the three carbon atoms of the original glycerol can be oxidized via glycolysis, or converted to glucose via gluconeogenesis.[10]
Other functions and uses of fatty acids[edit]
Intracellular signaling[edit]
Chemical structure of the diglyceride 1-palmitoyl-2-oleoyl-glycerol
Fatty acids are an integral part of the phospholipids that make up the bulk of the plasma membranes, or cell membranes, of cells. These phospholipids can be cleaved into diacylglycerol (DAG) and inositol trisphosphate (IP3) through hydrolysis of the phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2), by the cell membrane bound enzyme phospholipase C (PLC).[22]
An example of a diacyl-glycerol shown on the right. This DAG is 1-palmitoyl-2-oleoyl-glycerol, which contains side-chains derived from palmitic acid and oleic acid. Diacylglycerols can also have many other combinations of fatty acids attached at either the C-1 and C-2 positions or the C-1 and C-3 positions of the glycerol molecule. 1,2 disubstituted glycerols are always chiral, 1,3 disubstituted glycerols are chiral if the substituents are different from each other.
PIP2 cleavage to IP3 and DAG. IP3 initiates intracellular calcium release, while DAG activates PKC (protein kinase C). Note: PLC (phospholipase C) is not an intermediate, as possibly suggested by the diagram, but is the enzyme that catalyzes the IP3/DAG separation.[22]
Inositol trisphosphate (IP3) functions as an intracellular second messenger, which initiates the intracellular release of calcium ions (which activates intracellular enzymes, causes the release of hormones and neurotransmitters from the cells in which they are stored, and causes smooth muscle contraction when released by IP3), and the activation of protein kinase C (PKC), which is then translocated from the cell cytoplasm to the cell membrane. Although inositol trisphosphate, (IP3), diffuses into the cytosol, diacylglycerol (DAG) remains within the plasma membrane, due to its hydrophobic properties. IP3 stimulates the release of calcium ions from the smooth endoplasmic reticulum, whereas DAG is a physiological activator of protein kinase C (PKC), promoting its translocation from the cytosol to the plasma membrane. PKC is a multifunctional protein kinase which phosphorylates serine and threonine residues in many target proteins. However PKC is only active in the presence of calcium ions, and it is DAG that increases the affinity of PKC for Ca2+ and thereby renders it active at the physiological intracellular levels of this ion.[22]
Diacylglycerol and IP3 act transiently because both are rapidly metabolized. This is important as their message function should not linger after the message has been” received” by their target molecules. DAG can be phosphorylated to phosphatidate or it can be it can be hydrolysed to glycerol and its constituent fatty acids. IP3 is rapidly converted to into derivatives that that do not open calcium ion channels.[22]
Eicosanoid paracrine hormones[edit]
Arachidonic acid
Prostaglandin E1 - Alprostadil
The prostaglandins are a group of physiologically active lipid compounds having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are enzymatically derived from arachidonic acid a 20-carbon polyunsaturated fatty acid. Every prostaglandin therefore contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and form the prostanoid class of fatty acid derivatives.[23]
The prostaglandins are synthesized in the cell membrane by the cleavage of arachidonate from the phospholipids that make up the membrane. This is catalyzed either by phospholipase A2 acting directly on a membrane phospholipid, or by a lipase acting on DAG (diacyl-glycerol). The arachidonate is then acted upon by the cyclooxygenase component of prostaglandin synthase. This forms a cyclopentane ring in roughly the middle of the fatty acid chain. The reaction also adds 4 oxygen atoms derived from two molecules of O2. The resulting molecule is prostaglandin G2 which is converted by the hydroperoxidase component of the enzyme complex into prostaglandin H2. This highly unstable compound is rapidly transformed into other prostaglandins, prostacyclin and thromboxanes.[23] These are then released into the interstitial fluids surrounding the cells that have manufactured the eicosanoid hormone.
If arachidonate is acted upon by a lipoxygenase instead of cyclooxygenase, Hydroxyeicosatetraenoic acids and leukotrienes are formed. They also act as local hormones.
Prostaglandins were originally believed to leave the cells via passive diffusion because of their high lipophilicity. The discovery of the prostaglandin transporter (PGT, SLCO2A1), which mediates the cellular uptake of prostaglandin, demonstrated that diffusion alone cannot explain the penetration of prostaglandin through the cellular membrane. The release of prostaglandin has now also been shown to be mediated by a specific transporter, namely the multidrug resistance protein 4 (MRP4, ABCC4), a member of the ATP-binding cassette transporter superfamily. Whether MRP4 is the only transporter releasing prostaglandins from the cells is still unclear.
The structural differences between prostaglandins account for their different biological activities. A given prostaglandin may have different and even opposite effects in different tissues. The ability of the same prostaglandin to stimulate a reaction in one tissue and inhibit the same reaction in another tissue is determined by the type of receptor to which the prostaglandin binds. They act as autocrine or paracrine factors with their target cells present in the immediate vicinity of the site of their secretion. Prostaglandins differ from endocrine hormones in that they are not produced at a specific site but in many places throughout the human body.
Prostaglandins have two derivatives: prostacyclins and thromboxanes. Prostacyclins are powerful locally acting vasodilators and inhibit the aggregation of blood platelets. Through their role in vasodilation, prostacyclins are also involved in inflammation. They are synthesized in the walls of blood vessels and serve the physiological function of preventing needless clot formation, as well as regulating the contraction of smooth muscle tissue.[24] Conversely, thromboxanes (produced by platelet cells) are vasoconstrictors and facilitate platelet aggregation. Their name comes from their role in clot formation (thrombosis).
Dietary sources of fatty acids, their digestion, absorption, transport in the blood and storage[edit]
Dietary fats are emulsified in the duodenum by soaps in the form of bile salts and phospholipids, such as phosphatidylcholine. The fat droplets thus formed can be attacked by pancreatic lipase.
Structure of a bile acid (cholic acid), represented in the standard form, a semi-realistic 3D form, and a diagrammatic 3D form
Diagrammatic illustration of mixed micelles formed in the duodenum in the presence of bile acids (e.g. cholic acid) and the digestion products of fats, the fat soluble vitamins and cholesterol.
A significant proportion of the fatty acids in the body are obtained from the diet, in the form of triglycerides of either animal or plant origin. The fatty acids in the fats obtained from land animals tend to be saturated, whereas the fatty acids in the triglycerides of fish and plants are often polyunsaturated and therefore present as oils.
These triglycerides, cannot be absorbed by the intestine.[25] They are broken down into mono- and di-glycerides plus free fatty acids (but no free glycerol) by pancreatic lipase, which forms a 1:1 complex with a protein called colipase (also a constituent of pancreatic juice), which is necessary for its activity. The activated complex can work only at a water-fat interface. Therefore, it is essential that fats are first emulsified by bile salts for optimal activity of these enzymes.[26] The digestion products consisting of a mixture of tri-, di- and monoglycerides and free fatty acids, which, together with the other fat soluble contents of the diet (e.g. the fat soluble vitamins and cholesterol) and bile salts form mixed micelles, in the watery duodenal contents (see diagrams on the right).[25][27]
The contents of these micelles (but not the bile salts) enter the enterocytes (epithelial cells lining the small intestine) where they are resynthesized into triglycerides, and packaged into chylomicrons which are released into the lacteals (the capillaries of the lymph system of the intestines).[28] These lacteals drain into the thoracic duct which empties into the venous blood at the junction of the left jugular and left subclavian veins on the lower left hand side of the neck. This means that the fat soluble products of digestion are discharged directly into the general circulation, without first passing through the liver, as all other digestion products do. The reason for this peculiarity is unknown.[29]
A schematic diagram of a chylomicron.
The chylomicrons circulate throughout the body, giving the blood plasma a milky, or creamy appearance after a fatty meal.[citation needed] Lipoprotein lipase on the endothelial surfaces of the capillaries, especially in adipose tissue, but to a lesser extent also in other tissues, partially digests the chylomicrons into free fatty acids, glycerol and chylomicron remnants. The fatty acids are absorbed by the adipocytes[citation needed], but the glycerol and chylomicron remnants remain in the blood plasma, ultimately to be removed from the circulation by the liver. The free fatty acids released by the digestion of the chylomicrons are absorbed by the adipocytes[citation needed], where they are resynthesized into triglycerides using glycerol derived from glucose in the glycolytic pathway[citation needed]. These triglycerides are stored, until needed for the fuel requirements of other tissues, in the fat droplet of the adipocyte.
The liver absorbs a proportion of the glucose from the blood in the portal vein coming from the intestines. After the liver has replenished its glycogen stores (which amount to only about 100 g of glycogen when full) much of the rest of the glucose is converted into fatty acids as described below. These fatty acids are combined with glycerol to form triglycerides which are packaged into droplets very similar to chylomicrons, but known as very low-density lipoproteins (VLDL). These VLDL droplets are handled in exactly the same manner as chylomicrons, except that the VLDL remnant is known as an intermediate-density lipoprotein (IDL), which is capable of scavenging cholesterol from the blood. This converts IDL into low-density lipoprotein (LDL), which is taken up by cells that require cholesterol for incorporation into their cell membranes or for synthetic purposes (e.g. the formation of the steroid hormones). The remainder of the LDLs is removed by the liver.[30]
Adipose tissue and lactating mammary glands also take up glucose from the blood for conversion into triglycerides. This occurs in the same way as it does in the liver, except that these tissues do not release the triglycerides thus produced as VLDL into the blood. Adipose tissue cells store the triglycerides in their fat droplets, ultimately to release them again as free fatty acids and glycerol into the blood (as described above), when the plasma concentration of insulin is low, and that of glucagon and/or epinephrine is high.[31] Mammary glands discharge the fat (as cream fat droplets) into the milk that they produce under the influence of the anterior pituitary hormone prolactin.
All cells in the body need to manufacture and maintain their cell walls and the membranes of their organelles. Whether they rely for this entirely on free fatty acids absorbed from the blood, or are able to synthesize their own fatty acids from the blood glucose, is not known. The cells of the central nervous system will almost certainly have the capability of manufacturing their own fatty acids, as these molecules cannot reach them through the blood brain barrier, while, on the other hand, no cell in the body can manufacture the required essential fatty acids which have to be obtained from the diet and delivered to each cell via the blood.
Fatty acid synthesis[edit]
Main article: Fatty acid synthesis
Synthesis of saturated fatty acids via Fatty Acid Synthase II in E. coli
Much like beta-oxidation, straight-chain fatty acid synthesis occurs via the six recurring reactions shown below, until the 16-carbon palmitic acid is produced.[32][33]
The diagrams presented show how fatty acids are synthesized in microorganisms and list the enzymes found in Escherichia coli.[32] These reactions are performed by fatty acid synthase II (FASII), which in general contain multiple enzymes that act as one complex. FASII is present in prokaryotes, plants, fungi, and parasites, as well as in mitochondria.[34]
In animals, as well as some fungi such as yeast, these same reactions occur on fatty acid synthase I (FASI), a large dimeric protein that has all of the enzymatic activities required to create a fatty acid. FASI is less efficient than FASII; however, it allows for the formation of more molecules, including "medium-chain" fatty acids via early chain termination.[34]
Once 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.[35][36]
Step
Enzyme
Reaction
Description
(a) Acetyl CoA:ACP transacylase
Activates acetyl CoA for reaction with malonyl-ACP
(b) Malonyl CoA:ACP transacylase Activates malonyl CoA for reaction with acetyl-ACP
(c) 3-ketoacyl-ACP synthase
Reacts priming acetyl-ACP with chain-extending malonyl-ACP.
(d) 3-ketoacyl-ACP reductase
Reduces the carbon 3 ketone to a hydroxyl group
(e) 3-Hydroxyacyl ACP dehydrase
Removes water
(f) Enoyl-ACP reductase
Reduces the C2-C3 double bond.
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.[37] (Thus NADPH is also required for the synthesis of cholesterol from acetyl-CoA; while NADH is generated during glycolysis.) The source of the NADPH is two-fold. When malate is oxidatively decarboxylated by “NADP+-linked malic enzyme" pyruvate, CO2 and NADPH are formed. NADPH is also formed by the pentose phosphate pathway which converts glucose into ribose, which can be used in synthesis of nucleotides and nucleic acids, or it can be catabolized to pyruvate.[37]
Glycolytic end products are used in the conversion of carbohydrates into fatty acids[edit]
Main article: Citric acid cycle § Glycolytic end products are used in the conversion of carbohydrates into fatty acids
In humans, fatty acids are formed from carbohydrates predominantly in the liver and adipose tissue, as well as in the mammary glands during lactation. The cells of the central nervous system probably also make most of the fatty acids needed for the phospholipids of their extensive membranes from glucose, as blood-born fatty acids cannot cross the blood brain barrier to reach these cells.[37] 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.[37] 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.[37] 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).[38] The cytosolic acetyl-CoA is carboxylated by acetyl CoA carboxylase into malonyl CoA, the first committed step in the synthesis of fatty acids.[38][39]
Regulation of fatty acid synthesis[edit]
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 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 produce energy.[40]
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.[37][39]
Disorders[edit]
Disorders of fatty acid metabolism can be described in terms of, for example, hypertriglyceridemia (too high level of triglycerides), or other types of hyperlipidemia. These may be familial or acquired.
Familial types of disorders of fatty acid metabolism are generally classified as inborn errors of lipid 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.
References[edit]
^ Jump up to: a b c d e f Stryer, Lubert (1995). "Fatty acid metabolism.". In: Biochemistry. (Fourth ed.). New York: W.H. Freeman and Company. pp. 603–628. ISBN 0 7167 2009 4.
^ Jump up to: a b c d Oxidation of fatty acids
Jump up ^ Zechner R., Strauss J.G., Haemmerle G., Lass A., Zimmermann R. (2005). "Lipolysis: pathway under construction". Curr. Opin. Lipidol. 16: 333–340. CS1 maint: Multiple names: authors list (link)
Jump up ^ Mobilization and cellular uptake of stored fats (triacylglycerols) (with animation)
Jump up ^ Stahl, Andreas (1 February 2004). "A current review of fatty acid transport proteins (SLC27)". Pflügers Archiv European Journal of Physiology. 447 (5): 722–727. PMID 12856180. doi:10.1007/s00424-003-1106-z. Retrieved 2 March 2015.
Jump up ^ Anderson, Courtney M.; Stahl, Andreas (April 2013). "SLC27 fatty acid transport proteins". Molecular Aspects of Medicine. 34 (2–3): 516–528. doi:10.1016/j.mam.2012.07.010. Retrieved 2 March 2015.
Jump up ^ Ebert, D.; Haller, RG.; Walton, ME. (Jul 2003). "Energy contribution of octanoate to intact rat brain metabolism measured by 13C nuclear magnetic resonance spectroscopy". J Neurosci. 23 (13): 5928–35. PMID 12843297.
Jump up ^ Marin-Valencia, I.; Good, LB.; Ma, Q.; Malloy, CR.; Pascual, JM. (Feb 2013). "Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain". J Cereb Blood Flow Metab. 33 (2): 175–82. PMC 3564188  . PMID 23072752. doi:10.1038/jcbfm.2012.151.
Jump up ^ Stryer, Lubert (1995). "Fatty acid metabolism.". In: Biochemistry. (Fourth ed.). New York: W.H. Freeman and Company. pp. 770–771. ISBN 0 7167 2009 4.
^ Jump up to: a b c d e f g h i Stryer, Lubert (1995). Biochemistry. (Fourth ed.). New York: W.H. Freeman and Company. pp. 510–515, 581–613, 775–778. ISBN 0 7167 2009 4.
Jump up ^ Activation and transportation of fatty acids to the mitochondria via the carnitine shuttle (with animation)
Jump up ^ De Vivo D. C.; et al. (1998). "L-Carnitine Supplementation in Childhood Epilepsy: Current Perspectives". Epilepsia. 39 (11): 1216–1225. doi:10.1111/j.1528-1157.1998.tb01315.x. CS1 maint: Explicit use of et al. (link)
Jump up ^ Oxidation of odd carbon chain length fatty acids
Jump up ^ Oxidation of unsaturated fatty acids
Jump up ^ Stryer, Lubert (1995). Biochemistry. (Fourth ed.). New York: W.H. Freeman and Company. p. 777. ISBN 0 7167 2009 4.
Jump up ^ Sloan, A.W; Koeslag, J.H.; Bredell, G.A.G. (1973). "Body composition work capacity and work efficiency of active and inactive young men". European Journal of Applied Physiology. 32: 17–24. doi:10.1007/bf00422426.
Jump up ^ Ruddick JA (1972). "Toxicology, metabolism, and biochemistry of 1,2-propanediol". Toxicol App Pharmacol. 21: 102–111. doi:10.1016/0041-008X(72)90032-4.
^ Jump up to: a b c Glew, Robert H. "You Can Get There From Here: Acetone, Anionic Ketones and Even-Carbon Fatty Acids can Provide Substrates for Gluconeogenesis". Retrieved 7 August 2016.
^ Jump up to: a b c Park, Sung M.; Klapa, Maria I.; Sinskey, Anthony J.; Stephanopoulos, Gregory (1999). "Metabolite and isotopomer balancing in the analysis of metabolic cycles: II. Applications" (PDF). Biotechnology and Bioengineering. 62 (4): 398. ISSN 0006-3592.
Jump up ^ Miller DN, Bazzano G; Bazzano (1965). "Propanediol metabolism and its relation to lactic acid metabolism". Ann NY Acad Sci. 119 (3): 957–973. Bibcode:1965NYASA.119..957M. PMID 4285478. doi:10.1111/j.1749-6632.1965.tb47455.x.
Jump up ^ D. L. Vander Jagt; B. Robinson; K. K. Taylor; L. A. Hunsaker (1992). "Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications". The Journal of Biological Chemistry. 267 (7): 4364–4369. PMID 1537826.
^ Jump up to: a b c d Stryer, Lubert (1995). "Signal transduction cascades.". In: Biochemistry. (Fourth ed.). New York: W.H. Freeman and Company. pp. 343–350. ISBN 0 7167 2009 4.
^ Jump up to: a b Stryer, Lubert (1995). "Eicosanoid hormones are derived from fatty acids.". In: Biochemistry. (Fourth ed.). New York: W.H. Freeman and Company. pp. 624–627. ISBN 0 7167 2009 4.
Jump up ^ Nelson, Randy F. (2005). An introduction to behavioral endocrinology (3rd ed.). Sunderland, Mass: Sinauer Associates. p. 100. ISBN 0-87893-617-3.
^ Jump up to: a b Digestion of fats (triacylglycerols)
Jump up ^ Hofmann AF (1963). "The function of bile salts in fat absorption. The solvent properties of dilute micellar solutions of conjugated bile salts". Biochem. J. 89: 57–68. PMC 1202272  . PMID 14097367.
Jump up ^ Stryer, Lubert (1995). "Membrane structures and dynamics.". In: Biochemistry. (Fourth ed.). New York: W.H. Freeman and Company. pp. 268–270. ISBN 0 7167 2009 4.
Jump up ^ Smith, Sareen S. Gropper, Jack L.; Smith, Jack S (2013). Advanced nutrition and human metabolism (6th ed.). Belmont, CA: Wadsworth/Cengage Learning. ISBN 1133104053.
Jump up ^ Williams, Peter L.; Warwick, Roger; Dyson, Mary; Bannister, Lawrence H. (1989). "Angiology.". In: Gray’s Anatomy (Thirty-seventh ed.). Edinburgh: Churcill Livingstone. pp. 841–843. ISBN 0443 041776.
Jump up ^ Stryer, Lubert (1995). "Biosynthesis of membrane lipids and steroids.". In: Biochemistry. (Fourth ed.). New York: W.H. Freeman and Company. pp. 697–700. ISBN 0 7167 2009 4.
Jump up ^ Stralfors, Peter; Honnor, Rupert C. (1989). "Insulin-induced dephosphorylation of hormone-sensitive lipase". European Journal of Biochemistry. 182 (2): 379–385. doi:10.1111/j.1432-1033.1989.tb14842.x.
^ Jump up to: a b Dijkstra, Albert J., R. J. Hamilton, and Wolf Hamm. "Fatty Acid Biosynthesis." Trans Fatty Acids. Oxford: Blackwell Pub., 2008. 12. Print.
Jump up ^ "MetaCyc pathway: superpathway of fatty acids biosynthesis (E. coli)".
^ Jump up to: a b "Fatty Acids: Straight-chain Saturated, Structure, Occurrence and Biosynthesis." Lipid Library – Lipid Chemistry, Biology, Technology and Analysis. Web. 30 Apr. 2011. <http://lipidlibrary.aocs.org/lipids/fa_sat/index.htm>.
Jump up ^ "MetaCyc pathway: stearate biosynthesis I (animals)".
Jump up ^ "MetaCyc pathway: very long chain fatty acid biosynthesis II".
^ Jump up to: a b c d e f Stryer, Lubert (1995). Biochemistry. (Fourth ed.). New York: W.H. Freeman and Company. pp. 559–565, 614–623. ISBN 0 7167 2009 4.
^ Jump up to: a b Ferre, P.; F. Foufelle (2007). "SREBP-1c Transcription Factor and Lipid Homeostasis: Clinical Perspective". Hormone Research. 68 (2): 72–82. PMID 17344645. doi:10.1159/000100426. Retrieved 2010-08-30. this process is outlined graphically in page 73
^ Jump up to: a b Voet, Donald; Judith G. Voet; Charlotte W. Pratt (2006). Fundamentals of Biochemistry, 2nd Edition. John Wiley and Sons, Inc. pp. 547, 556. ISBN 0-471-21495-7.
Jump up ^ Diwan, Joyce J. "Fatty Acid Synthesis." Rensselaer Polytechnic Institute (RPI) :: Architecture, Business, Engineering, IT, Humanities, Science. Web. 30 Apr. 2011. <http://rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/fasynthesis.htm>.
[show]
v
t
e
Metabolism, catabolism, anabolism
General
Metabolic pathway
Metabolic network
Primary nutritional groups
Energy
metabolism
Aerobic respiration
Glycolysis → Pyruvate decarboxylation → Citric acid cycle → Oxidative phosphorylation (electron transport chain + ATP synthase)
Anaerobic respiration
Electron acceptors are other than oxygen
Fermentation
Glycolysis →
Substrate-level phosphorylation
ABE
Ethanol
Lactic acid
Specific
paths
Protein metabolism
Protein synthesis
Catabolism
Carbohydrate metabolism
(carbohydrate catabolism
and anabolism)
Human
Glycolysis ⇄ Gluconeogenesis
Glycogenolysis ⇄ Glycogenesis
Pentose phosphate pathway
Fructolysis
Galactolysis
Glycosylation
N-linked
O-linked
Nonhuman
Photosynthesis
Anoxygenic photosynthesis
Chemosynthesis
Carbon fixation
Xylose metabolism
Radiotrophism
Lipid metabolism
(lipolysis, lipogenesis)
Fatty acid metabolism
Fatty acid degradation (Beta oxidation)
Fatty acid synthesis
Other
Steroid metabolism
Sphingolipid metabolism
Eicosanoid metabolism
Ketosis
Reverse cholesterol transport
Amino acid
Amino acid synthesis
Urea cycle
Nucleotide
metabolism
Purine metabolism
Nucleotide salvage
Pyrimidine metabolism
Other
Metal metabolism
Iron metabolism
Ethanol metabolism
[show]
v
t
e
Metabolism map
Carbon
Fixation
Photo-
respiration
Pentose
Phosphate
Pathway
Citric
Acid Cycle
Glyoxylate
Cycle
Urea
Cycle
Fatty
Acid
Synthesis
Fatty
Acid
Elongation
Beta
Oxidation
Peroxisomal
Beta
Oxidation

Glyco-
genolysis
Glyco-
genesis
Glyco-
lysis
Gluconeo-
genesis
Decarb-
oxylation
Fermentation
Keto-
lysis
Keto-
genesis
feeders to
Gluconeo-
genesis
Direct / C4 / CAM
Carbon Intake
Light Reaction
Oxidative
Phosphorylation
Amino Acid
Deamination
Citrate
Shuttle
Lipogenesis
Lipolysis
Steroidogenesis
MVA Pathway
MEP Pathway
Shikimate
Pathway
Transcription &
Replication
Translation
Proteolysis
Glycosy-
lation

Sugar
Acids
Double/Multiple
Sugars & Glycans
Simple
Sugars
Inositol-P
Amino Sugars
& Sialic Acids
Nucleotide Sugars
Hexose-P
Triose-P
Glycerol
P-glycerates
Pentose-P
Tetrose-P
Propionyl
-CoA
Succinate
Acetyl
-CoA
Pentose-P
P-glycerates
Glyoxylate
Photosystems
Pyruvate
Lactate
Acetyl
-CoA
Citrate
Oxalo-
acetate
Malate
Succinyl
-CoA
α-Keto-
glutarate
Ketone
Bodies
Respiratory
Chain
Serine Group
Alanine
Branched-chain
Amino Acids
Aspartate
Group
Homoserine
Group
& Lysine
Glutamate
Group
& Proline
Arginine
Creatine
& Polyamines
Ketogenic &
Glucogenic
Amino Acids
Amino Acids
Shikimate
Aromatic Amino
Acids & Histidine
Ascorbate
(Vitamin C)
δ-ALA
Bile
Pigments
Hemes
Cobalamins (Vitamin B12)
Various
Vitamin B's
Calciferols
(Vitamin D)
Retinoids
(Vitamin A)
Quinones (Vitamin K)
& Carotenoids (Vitamin E)
Cofactors
Vitamins
& Minerals
Antioxidants
PRPP
Nucleotides
Nucleic
Acids
Proteins
Glycoproteins
& Proteoglycans
Chlorophylls
MEP
MVA
Acetyl
-CoA
Polyketides
Terpenoid
Backbones
Terpenoids
& Carotenoids (Vitamin A)
Cholesterol
Bile Acids
Glycero-
phospholipids
Glycerolipids
Acyl-CoA
Fatty
Acids
Glyco-
sphingolipids
Sphingolipids
Waxes
Polyunsaturated
Fatty Acids
Neurotransmitters
& Thyroid Hormones
Steroids
Endo-
cannabinoids
Eicosanoids
Major metabolic pathways in metro-style map. Click any text (name of pathway or metabolites) to link to the corresponding article.
Single lines: pathways common to most lifeforms. Double lines: pathways not in humans (occurs in e.g. plants, fungi, prokaryotes). Orange nodes: carbohydrate metabolism. Violet nodes: photosynthesis. Red nodes: cellular respiration. Pink nodes: cell signaling. Blue nodes: amino acid metabolism. Grey nodes: vitamin and cofactor metabolism. Brown nodes: nucleotide and protein metabolism. Green nodes: lipid metabolism.
[show]
v
t
e
Metabolism: lipid metabolism / fatty acid metabolism, triglyceride and fatty acid enzymes
Synthesis
Malonyl-CoA synthesis
ATP citrate lyase
Acetyl-CoA carboxylase
Fatty acid synthesis/
Fatty acid synthase
Beta-ketoacyl-ACP synthase
Β-Ketoacyl ACP reductase
3-Hydroxyacyl ACP dehydrase
Enoyl ACP reductase
Fatty acid desaturases
Stearoyl-CoA desaturase-1
Triacyl glycerol
Glycerol-3-phosphate dehydrogenase
Thiokinase
Degradation
Acyl transport
Carnitine palmitoyltransferase I
Carnitine-acylcarnitine translocase
Carnitine palmitoyltransferase II
Beta oxidation
General
Acyl CoA dehydrogenase (ACADL
ACADM
ACADS
ACADVL
ACADSB)
Enoyl-CoA hydratase
MTP: HADH
HADHA
HADHB
Acetyl-CoA C-acyltransferase
Unsaturated
Enoyl CoA isomerase
2,4 Dienoyl-CoA reductase
Odd chain
Propionyl-CoA carboxylase
Other
Hydroxyacyl-Coenzyme A dehydrogenase
To acetyl-CoA
Malonyl-CoA decarboxylase
Aldehydes
Long-chain-aldehyde dehydrogenase
Retrieved from "https://en.wikipedia.org/w/index.php?title=Fatty_acid_metabolism&oldid=801248833"
Categories:
Metabolism
Fatty acids
Hepatology
Hidden categories:
CS1 maint: Multiple names: authors list
CS1 maint: Explicit use of et al.
All articles with unsourced statements
Articles with unsourced statements from September 2017
Navigation menu
Personal tools
Not logged in
Talk
Contributions
Create account
Log in
Namespaces
Article
Talk
Variants
Views
Read
Edit
View history
More
Search
Navigation
Main page
Contents
Featured content
Current events
Random article
Donate to Wikipedia
Wikipedia store
Interaction
Help
About Wikipedia
Community portal
Recent changes
Contact page
Tools
What links here
Related changes
Upload file
Special pages
Permanent link
Page information
Wikidata item
Cite this page
Print/export
Create a book
Download as PDF
Printable version
Languages
العربية
Català
Čeština
Dansk
Deutsch
Español
Italiano
Српски / srpski
Srpskohrvatski / српскохрватски
Türkçe
中文
Edit links
This page was last edited on 18 September 2017, at 15:55.
Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization.
Privacy policy
About Wikipedia
Disclaimers
Contact Wikipedia
Developers
Cookie statement
Mobile view

values: mw-page-base noprint

values: mw-head-base noprint

attrs: id class style

values: firstHeading firstHeading en

values: siteSub noprint

values: jump-to-nav mw-jump

value: b

values: /wiki/Catabolic mw-redirect Catabolic

values: /wiki/Anabolic mw-redirect Anabolic

values:
/wiki/Fatty_acids
mw-redirect
Fatty acids

value: sub

values:
/wiki/Phospholipid_bilayers
mw-redirect
Phospholipid bilayers

values:
/wiki/Second_messenger
mw-redirect
Second messenger

attrs: alt src width height class srcset data-file-width data-file-height

values:
/wiki/Free_fatty_acids
mw-redirect
Free fatty acids

values:
/wiki/Transport_proteins
mw-redirect
Transport proteins

values:
/wiki/Blood_brain_barrier
mw-redirect
Blood brain barrier

values:
/wiki/Outer_mitochondrial_membrane
mw-redirect
Outer mitochondrial membrane

values:
/wiki/Acyl-CoA_dehydrogenase
mw-redirect
Acyl-CoA dehydrogenase

values:
/wiki/Blood-brain_barrier
mw-redirect
Blood-brain barrier

values:
/wiki/Triose_phosphate_isomerase
mw-redirect
Triose phosphate isomerase

values: Edit section: Fatty acids as an energy source

values:
/wiki/Alpha-linolenic_acid
mw-redirect
Alpha-linolenic acid

values: Edit section: Animals and plants synthesize carbohydrates from both glycerol and fatty acids

values:
/wiki/Alpha-ketoglutarate_dehydrogenase
mw-redirect
Alpha-ketoglutarate dehydrogenase

values:
/wiki/Isotopic_labelling
mw-redirect
Isotopic labelling

values: Edit section: Other functions and uses of fatty acids

values:
/wiki/Plasma_membrane
mw-redirect
Plasma membrane

values:
/wiki/Smooth_muscle
mw-redirect
Smooth muscle

values: Edit section: Eicosanoid paracrine hormones

values:
/wiki/Carbon_ring
mw-redirect
Carbon ring

values:
/wiki/Prostaglandin_synthase
mw-redirect
Prostaglandin synthase

values:
/wiki/Prostaglandin_transporter
mw-redirect
Prostaglandin transporter

values:
/wiki/Multidrug_resistance_protein_4
mw-redirect
Multidrug resistance protein 4

values: Edit section: Dietary sources of fatty acids, their digestion, absorption, transport in the blood and storage

values:
/wiki/Pancreatic_lipase
mw-redirect
Pancreatic lipase

values:
/wiki/Lymph_system
mw-redirect
Lymph system

values: This claim needs references to reliable sources. (September 2017)

values:
noprint Inline-Template Template-Fact
white-space:nowrap;

values:
/wiki/Steroid_hormones
mw-redirect
Steroid hormones

values: Nicotinamide adenine dinucleotide phosphate

values:
/wiki/Nucleic_acids
mw-redirect
Nucleic acids

values: Edit section: Glycolytic end products are used in the conversion of carbohydrates into fatty acids

values:
/wiki/Mammary_glands
mw-redirect
Mammary glands

values:
/wiki/Acetyl_CoA_carboxylase
mw-redirect
Acetyl CoA carboxylase

values: Edit section: Regulation of fatty acid synthesis

values:
/wiki/Krebs_cycle
mw-redirect
Krebs cycle

values:
/wiki/Inborn_errors_of_lipid_metabolism
mw-redirect
Inborn errors of lipid metabolism

values:
/wiki/Fatty_oxidation_disorder
mw-redirect
Fatty oxidation disorder

values:
/wiki/Inborn_errors_of_metabolism
mw-redirect
Inborn errors of metabolism

values: Category:CS1 maint: Multiple names: authors list

values:
/wiki/PubMed_Identifier
mw-redirect
PubMed Identifier

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/12856180

values:
nofollow
external text
//doi.org/10.1007%2Fs00424-003-1106-z

values:
nofollow
external text
//doi.org/10.1016%2Fj.mam.2012.07.010

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/12843297

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23072752

values:
nofollow
external text
//doi.org/10.1038%2Fjcbfm.2012.151

values: Category:CS1 maint: Explicit use of et al.

values:
nofollow
external text
//doi.org/10.1007%2Fbf00422426

values:
nofollow
external text
//www.worldcat.org/issn/0006-3592

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/4285478

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/1537826

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/14097367

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/17344645

values:
nofollow
external text
//doi.org/10.1159%2F000100426

values: -moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;

values:
/wiki/Aerobic_respiration
mw-redirect
Aerobic respiration

values:
/wiki/Sphingolipid_metabolism
mw-redirect
Sphingolipid metabolism

values:
/wiki/Eicosanoid_metabolism
mw-redirect
Eicosanoid metabolism

values: nowraplinks hlist collapsible autocollapse navbox-inner

values: Metro-style map of major metabolic pathways

values: left:0px; top:0px; width:800px; position:absolute

values: position:absolute; left:225px; top:150px; font-size:15px; line-height:17px;

values: position:absolute; left:135px; top:185px; font-size:15px; line-height:17px;

values: position:absolute; left:395px; top:140px; font-size:15px; line-height:17px;

values: position:absolute; left:215px; top:340px; font-size:15px; line-height:17px;

values: position:absolute; left:365px; top:505px; font-size:15px; line-height:17px;

values: position:absolute; left:125px; top:398px; font-size:15px; line-height:17px;

values: position:absolute; left:495px; top:260px; font-size:15px; line-height:17px;

values: position:absolute; left:495px; top:335px; font-size:15px; line-height:17px;

values: position:absolute; left:497px; top:425px; font-size:15px; line-height:17px;

values: position:absolute; left:495px; top:495px; font-size:12px; line-height:14px;

values: position:absolute; left:497px; top:510px; font-size:15px; line-height:17px;

values: position:absolute; left:295px; top:42px; font-size:9px; line-height:11px; text-align:right;

values: position:absolute; left:280px; top:80px; font-size:9px; line-height:11px; text-align:left;

values: position:absolute; left:360px; top:160px; font-size:9px; line-height:11px; text-align:left;

values: position:absolute; left:300px; top:160px; font-size:9px; line-height:11px; text-align:right;

values: position:absolute; left:310px; top:340px; font-size:9px; line-height:11px; text-align:right;

values: position:absolute; left:365px; top:335px; font-size:9px; line-height:11px;

values: position:absolute; left:325px; top:430px; font-size:9px; line-height:11px; text-align:right;

values: position:absolute; left:365px; top:430px; font-size:9px; line-height:11px; text-align:left;

values: position:absolute; left:195px; top:470px; font-size:9px; line-height:11px; text-align:left;

values: position:absolute; left:225px; top:230px; font-size:9px; line-height:11px; text-align:right;

values: position:absolute; left:125px; top:143px; font-size:9px; line-height:11px;

values: position:absolute; left:115px; top:355px; font-size:9px; line-height:11px;

values: position:absolute; left:25px; top:415px; font-size:9px; line-height:11px;

values: position:absolute; left:315px; top:288px; font-size:9px; line-height:11px;

values: position:absolute; left:590px; top:415px; font-size:9px; line-height:11px; text-align:left;

values: position:absolute; left:590px; top:455px; font-size:9px; line-height:11px; text-align:left;

values: position:absolute; left:585px; top:260px; font-size:9px; line-height:11px;

values: position:absolute; left:470px; top:235px; font-size:9px; line-height:11px;

values: position:absolute; left:460px; top:210px; font-size:9px; line-height:11px;

values: position:absolute; left:487px; top:153px; font-size:9px; line-height:11px;

values:
/wiki/Transcription_(genetics)
mw-redirect
Transcription (genetics)

values: position:absolute; left:555px; top:105px; font-size:9px; line-height:11px;

values: position:absolute; left:600px; top:83px; font-size:9px; line-height:11px;

values: position:absolute; left:600px; top:57px; font-size:9px; line-height:11px;

values: position:absolute; left:690px; top:55px; font-size:9px; line-height:11px;

values: position:absolute; left:210px; top:38px; line-height:110%

values: position:absolute; left:240px; top:38px; line-height:110%

values: position:absolute; left:340px; top:38px; line-height:110%

values: position:absolute; left:380px; top:45px; line-height:110%

values: position:absolute; left:160px; top:90px; line-height:110%

values: position:absolute; left:245px; top:120px; line-height:110%

values: position:absolute; left:365px; top:105px; line-height:110%

values: position:absolute; left:315px; top:180px; line-height:110%

values: position:absolute; left:305px; top:240px; line-height:110%

values: position:absolute; left:300px; top:260px; line-height:110%

values: position:absolute; left:425px; top:110px; line-height:110%

values: position:absolute; left:470px; top:190px; line-height:110%

values: position:absolute; left:410px; top:440px; line-height:110%

values: position:absolute; left:310px; top:495px; line-height:110%

values: position:absolute; left:455px; top:530px; line-height:110%

values: position:absolute; left:150px; top:155px; line-height:110%

values: position:absolute; left:230px; top:210px; line-height:110%

values: position:absolute; left:85px; top:180px; line-height:110%

values: position:absolute; left:65px; top:152px; line-height:110%

values: position:absolute; left:320px; top:310px; line-height:110%

values: position:absolute; left:410px; top:308px; line-height:110%

values: position:absolute; left:365px; top:345px; line-height:110%

values: position:absolute; left:295px; top:380px; line-height:110%

values: position:absolute; left:270px; top:300px; line-height:110%

values: position:absolute; left:200px; top:310px; line-height:110%

values: position:absolute; left:195px; top:405px; line-height:110%

values: position:absolute; left:275px; top:405px; line-height:110%

values: position:absolute; left:370px; top:455px; line-height:110%

values: position:absolute; left:70px; top:365px; line-height:110%

values: position:absolute; left:370px; top:265px; line-height:110%

values: position:absolute; left:395px; top:290px; line-height:110%

values: position:absolute; left:415px; top:345px; line-height:110%

values: position:absolute; left:275px; top:275px; line-height:110%

values: position:absolute; left:180px; top:250px; line-height:110%

values: position:absolute; left:280px; top:445px; line-height:110%

values: position:absolute; left:105px; top:465px; line-height:110%

values: position:absolute; left:40px; top:465px; line-height:110%

values: position:absolute; left:415px; top:385px; line-height:110%

values: position:absolute; left:550px; top:85px; line-height:110%

values: position:absolute; left:520px; top:190px; line-height:110%

values: position:absolute; left:635px; top:165px; line-height:110%

values: position:absolute; left:158px; top:38px; line-height:110%

values: position:absolute; left:275px; top:490px; line-height:110%

values:
/wiki/Bile_pigment
mw-redirect
Bile pigment

values: position:absolute; left:155px; top:510px; line-height:110%

values: position:absolute; left:210px; top:520px; line-height:110%

values: position:absolute; left:245px; top:585px; line-height:110%

values: position:absolute; left:425px; top:45px; line-height:110%

values: position:absolute; left:625px; top:300px; line-height:110%

values: position:absolute; left:725px; top:235px; line-height:110%

values: position:absolute; left:590px; top:190px; line-height:110%

values: position:absolute; left:665px; top:140px; line-height:110%

values: position:absolute; left:745px; top:140px; line-height:110%

values: position:absolute; left:720px; top:185px; line-height:110%

values: position:absolute; left:490px; top:140px; line-height:110%

values: position:absolute; left:535px; top:140px; line-height:110%

values: position:absolute; left:610px; top:140px; line-height:110%

values: position:absolute; left:665px; top:87px; line-height:110%

values: position:absolute; left:710px; top:87px; line-height:110%

values: position:absolute; left:280px; top:520px; line-height:110%

values:
/wiki/Methylerythritol_phosphate
mw-redirect
Methylerythritol phosphate

values: position:absolute; left:410px; top:235px; line-height:110%

values: position:absolute; left:420px; top:245px; line-height:110%

values: position:absolute; left:420px; top:260px; line-height:110%

values: position:absolute; left:440px; top:330px; line-height:110%

values: position:absolute; left:555px; top:230px; line-height:110%

values: position:absolute; left:625px; top:235px; line-height:110%

values: position:absolute; left:640px; top:287px; line-height:110%

values: position:absolute; left:720px; top:287px; line-height:110%

values: position:absolute; left:640px; top:330px; line-height:110%

values: position:absolute; left:600px; top:397px; line-height:110%

values: position:absolute; left:620px; top:430px; line-height:110%

values: position:absolute; left:630px; top:500px; line-height:110%

values: position:absolute; left:720px; top:350px; line-height:110%

values: position:absolute; left:720px; top:397px; line-height:110%

values: position:absolute; left:720px; top:440px; line-height:110%

values: position:absolute; left:680px; top:497px; line-height:110%

values:
/wiki/Thyroid_hormone
mw-redirect
Thyroid hormone

values: position:absolute; left:470px; top:45px; line-height:110%

values: position:absolute; left:705px; top:305px; line-height:110%

values: position:absolute; left:587px; top:330px; line-height:110%

values: position:absolute; left:735px; top:465px; line-height:110%

values: position:relative; width:800px; height:600px; overflow:hidden; border:solid #ccc 1px; background-color:white;

values: The image above contains clickable links

values:
/wiki/Metabolic_pathways
mw-redirect
Metabolic pathways

values:
/wiki/Amino_acid_metabolism
mw-redirect
Amino acid metabolism

values:
thumb center thumbinner
margin: 1em auto; width:802px;

values: margin-left: auto; margin-right: auto; border: none;

values: nowraplinks collapsible collapsed navbox-inner

values: Template talk:Lipid metabolism enzymes (page does not exist)

values:
/wiki/%CE%92-Ketoacyl_ACP_reductase
mw-redirect
Β-Ketoacyl ACP reductase

values:
/wiki/Enoyl_ACP_reductase
mw-redirect
Enoyl ACP reductase

values:
/wiki/Acetyl-CoA_C-acyltransferase
mw-redirect
Acetyl-CoA C-acyltransferase

values: nowraplinks collapsible autocollapse navbox-inner

values: Category:All articles with unsourced statements

values: Category:Articles with unsourced statements from September 2017

values: Discussion about edits from this IP address [ctrl-alt-n]

values: A list of edits made from this IP address [ctrl-alt-y]

values: You are encouraged to create an account and log in; however, it is not mandatory

values: You're encouraged to log in; however, it's not mandatory. [ctrl-alt-o]

values:
/wiki/Fatty_acid_metabolism
View the content page [ctrl-alt-c]
c

values: Discussion about the content page [ctrl-alt-t]

values: p-namespaces navigation vectorTabs p-namespaces-label

values:
p-variants
navigation
vectorMenu emptyPortlet
p-variants-label

values: Past revisions of this page [ctrl-alt-h]

values: p-views navigation vectorTabs p-views-label

values:
p-cactions
navigation
vectorMenu emptyPortlet
p-cactions-label

values:
mw-wiki-logo
/wiki/Main_Page
Visit the main page

values:
/wiki/Main_Page
Visit the main page [ctrl-alt-z]
z

values: Featured content – the best of Wikipedia

values: Find background information on current events

values:
/wiki/Special:Random
Load a random article [ctrl-alt-x]
x

values: portal navigation p-navigation p-navigation-label

values: Guidance on how to use and edit Wikipedia

values: About the project, what you can do, where to find things

values: A list of recent changes in the wiki [ctrl-alt-r]

values: portal navigation p-interaction p-interaction-label

values: List of all English Wikipedia pages containing links to this page [ctrl-alt-j]

values: Recent changes in pages linked from this page [ctrl-alt-k]

values:
/wiki/Wikipedia:File_Upload_Wizard
Upload files [ctrl-alt-u]
u

values: A list of all special pages [ctrl-alt-q]

values: Permanent link to this revision of the page

values: Link to connected data repository item [ctrl-alt-g]

values: Printable version of this page [ctrl-alt-p]

values:
uls-settings-trigger
Language settings
0
button
true

values: أيض الحموض الدهنية – Arabic

values: Metabolisme dels àcids grassos – Catalan

values: Metabolismo de los ácidos grasos – Spanish

values: Metabolizam masnih kiselina – Serbo-Croatian

values: mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-0 ns-subject page-Fatty_acid_metabolism rootpage-Fatty_acid_metabolism vector-nav-directionality skin-vector action-view


text:
Zuchon
From Wikipedia, the free encyclopedia
This is the current revision of this page, as edited by 2600:387:0:803::b5 (talk) at 21:56, 28 July 2017 (Removed reference to "teddy bear puppy" as source indicates the term is used to describe many different hybrids.). The present address (URL) is a permanent link to this version.
Revision as of 21:56, 28 July 2017 by 2600:387:0:803::b5 (talk) (Removed reference to "teddy bear puppy" as source indicates the term is used to describe many different hybrids.)
(diff) ← Previous revision | Latest revision (diff) | Newer revision → (diff)
Jump to: navigation, search
Zuchon
Other names
Shichon, Teddy Bear
Origin
United States
Foundation stock
Crossbreed of Bichon Frisé x Shih Tzu
[hide]Traits
Weight
7 - 15 lbs.
Height
9 - 12 inches tall
Life span
average 12-15 years
Domestic dog (Canis lupus familiaris)
Zuchon or Shichon is a hybrid breed dog or a designer dog. It is cross between Bichon Frisé and Shih Tzu.[1]
The Zuchon is a small designer dog with a height around 12 inches and weighing 12 to 14 pounds. Zuchon is a portmanteau name combining the two breed names and is not accepted as a breed by the AKC or any other major recognised dog breed registry. [2] It is a dog that does not shed but it also requires maintenance with regular grooming. Because it is a hybrid dog from two purebreds, it is known to have hybrid vigor, when they are first generation, could possibly have better health than the purebred dogs. [3] However, if they are not first generation, health problems can exist. The dog breed has a short history beginning only at the turn of the 21st century. [3]
Contents
[hide]
1 Appearance
2 Temperament
3 Health
4 History
5 References
6 External links
Appearance[edit]
The Zuchon is also known as a Shichon or, less commonly, a Tzu Frise.[4] They reach an average height of 9-12 inches from the shoulder, and a weight of 8-25 pounds fully grown. 'Dog Breed Info' says the Zuchon is a dog "known for his endearing face, large expressive eyes, and his soft teddy-bear coat."[3]
The Zuchon usually has a longer coat that does not shed very much, if at all. This longer coat may lead to more time for maintenance and grooming.[3][5]
As hypoallergenic dogs, Zuchons are generally more suitable for homes with allergy problems amongst the inhabitants, although allergic reactions may still occur.[6]
Temperament[edit]
This toy dog is said to have a "great" personality, and it is playful, lively and well-mannered.[3] They can be a bit stubborn, but when they are trained well, they are a good family pet.[2] They are easily trained.[2]
The Zuchon is a well-mannered dog known to be social, happy, and gentle. They become devoted to their families but need much attention and do not do well when left alone for long periods of time.[7] They are good therapy dogs.[5] Sometimes the Zuchon may be stubborn and in need of training. The Zuchon will remain active.[2][3][8]
They make fairly good watch dogs. When necessary, this dog will bark to alert its family that someone is nearby. This breed is typically good with other pets, especially when socialized at an early age. This dog gets along well with children, but it may be a good idea to socialize this breed at an early age as well as to supervise play time with children to make sure that the dog does not get hurt as a result of its small size.
Health[edit]
An important feature with the Zuchon hybrid breed is its longevity. The average life-expectancy of a Zuchon is around 12–15 years.[3][9][5] The Zuchon, like many hybrid breeds, is usually healthy without showing the congenital defects that purebreds can have from inbreeding. However, this is only true if the Zuchon is a first generation dog.[2] When a multi-generation Zuchon is born, the possibility of health issues increases. Some possible defects known to designer dogs include canine hip dysplasia, deafness, epilepsy, and liver disease.[5][10]
History[edit]
Americans began breeding designer dogs in the 1990s.[11] The Zuchon is a cross between an oriental Shih Tzu and a Mediterranean Bichon Frisé. Although this breed of dog is relatively new, its popularity and fame is growing quickly.[2] The Zuchon is still not thought of as an official breed of dog, only a cross-breed. This may change as the dog is becoming a popular toy dog being classified with all other toy dog purebreds. Organizations that recognise this breed include the American Canine Hybrid Club and the Designer Dogs Kennel Club.[2][3]
References[edit]
Jump up ^ "AMERICAN CANINE HYBRID CLUB HYBRID BREEDS". American Canine Hybrid Club. 2014. Retrieved 14 February 2015.
^ Jump up to: a b c d e f g Zuchon Characteristics, tinytracks.net, 2001, accessed October 20, 2009.
^ Jump up to: a b c d e f g h Shichhon Information Archived August 22, 2009, at the Wayback Machine., dogpage.us, 1997, accessed October 20, 2009.
Jump up ^ "What is a Teddy Bear Puppy?". Mini Teddy Bear Puppies. Retrieved 29 December 2015.
^ Jump up to: a b c d All You Need To Know About The Bichon Frise Shih Tzu Mix, http://www.dogtemperament.com/,[permanent dead link] accessed February 12, 2015.
Jump up ^ Hypoallergenic Dogs, puppy-basics.com, 2005, accessed October 21, 2009.
Jump up ^ Dejong, Fifi (January 11, 2014). "ABC Dogs Book". Rikhi Publishing. Retrieved February 16, 2012.
Jump up ^ Character of Shichon, http://www.shichondog.com/ 2011, accessed February 12, 2015.
Jump up ^ Small Vs. Large Dog, smalldogsparadise.com, 2006, accessed October 20, 2009.
Jump up ^ Health Concerns for Dogs Archived February 2, 2012, at the Wayback Machine., ecsca.org, 2009, accessed October 20, 2009.
Jump up ^ Mooallem, Jon (February 4, 2007). "The Modern Kennel Conundrum". The New York Times. Retrieved February 16, 2015.
External links[edit]
Official website
Zuchon, Petguide.com
Shichon, Dog Breed Plus
Teddy Bear Puppies, Teddy Bear Dogs! Facts and Information. the Complete Owner's Guide to the Dogs That Look Like Teddy Bears: Teddy Bear Dogs, Shichons, Zuchons. Buckley, Joseph. October 8, 2014. ISBN 9780990607212.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Zuchon&oldid=792817917"
Categories:
Dog breeds originating in the United States
Dog crossbreeds
Toy dogs
Companion dogs
Hidden categories:
Webarchive template wayback links
All articles with dead external links
Articles with dead external links from July 2016
Articles with permanently dead external links
Articles with 'species' microformats
Navigation menu
Personal tools
Not logged in
Talk
Contributions
Create account
Log in
Namespaces
Article
Talk
Variants
Views
Read
Edit
View history
More
Search
Navigation
Main page
Contents
Featured content
Current events
Random article
Donate to Wikipedia
Wikipedia store
Interaction
Help
About Wikipedia
Community portal
Recent changes
Contact page
Tools
What links here
Related changes
Upload file
Special pages
Permanent link
Page information
Wikidata item
Cite this page
Print/export
Create a book
Download as PDF
Printable version
Languages
Español
Edit links
This page was last edited on 28 July 2017, at 21:56.
Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization.
Privacy policy
About Wikipedia
Disclaimers
Contact Wikipedia
Developers
Cookie statement
Mobile view
Enable previews

key: html

type: local

value: div

attrs: id class

values: mw-page-base noprint

values: mw-head-base noprint

value: a

attrs: id class lang

values: firstHeading firstHeading en

values: siteSub noprint

attrs: href title

value: bdi

attrs: href class title

value: span

value: td

value: tr

value: tbody

value: table

attrs: id class role

values:
revision-info-current
plainlinks fmbox fmbox-system
presentation

attrs: alt src width height srcset data-file-width data-file-height

values:
/wiki/Bichon_Fris%C3%A9
mw-redirect
Bichon Frisé

values:
/wiki/Dog_crossbreeds
mw-redirect
Dog crossbreeds

values:
/wiki/Designer_dog
mw-redirect
Designer dog

values:
nofollow
http://www.dogtemperament.com/
external free

values:
nofollow
http://www.shichondog.com/
external text

values:
nofollow
http://www.shichondog.com/
external free

values:
nofollow
external text
http://www.ecsca.org/healthcon.html

values: Category:Dog breeds originating in the United States

values: Category:Webarchive template wayback links

values: Category:All articles with dead external links

values: Category:Articles with dead external links from July 2016

values: Category:Articles with permanently dead external links

values: Category:Articles with 'species' microformats

values: Discussion about edits from this IP address [ctrl-alt-n]

values: A list of edits made from this IP address [ctrl-alt-y]

values: You are encouraged to create an account and log in; however, it is not mandatory

values: You're encouraged to log in; however, it's not mandatory. [ctrl-alt-o]

values:
/wiki/Zuchon
View the content page [ctrl-alt-c]
c

values: Discussion about the content page [ctrl-alt-t]

values: p-namespaces navigation vectorTabs p-namespaces-label

values:
p-variants
navigation
vectorMenu emptyPortlet
p-variants-label

values:
/w/index.php?title=Zuchon&action=edit
Edit this page [ctrl-alt-e]
e

values: Past revisions of this page [ctrl-alt-h]

values: p-views navigation vectorTabs p-views-label

values:
p-cactions
navigation
vectorMenu emptyPortlet
p-cactions-label

values:
mw-wiki-logo
/wiki/Main_Page
Visit the main page

values:
/wiki/Main_Page
Visit the main page [ctrl-alt-z]
z

values: Featured content – the best of Wikipedia

values: Find background information on current events

values:
/wiki/Special:Random
Load a random article [ctrl-alt-x]
x

values: portal navigation p-navigation p-navigation-label

values:
https://es.wikipedia.org/wiki/Zuchon
Zuchon – Spanish
es
es
interlanguage-link-target

values: /static/images/wikimedia-button-1.5x.png 1.5x, /static/images/wikimedia-button-2x.png 2x

values: /static/images/poweredby_mediawiki_132x47.png 1.5x, /static/images/poweredby_mediawiki_176x62.png 2x

values:
suggestions
display: none; font-size: 13px;

values: mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-0 ns-subject page-Zuchon rootpage-Zuchon skin-vector action-view