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CD36

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The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD ) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as receptors or ligands important to the cell. A signal cascade is usually initiated, altering the behavior of the cell (see cell signaling ). Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion . CD for humans is numbered up to 371 (as of 21 April 2016 ).

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79-821: 948 12491 ENSG00000135218 ENSMUSG00000002944 P16671 Q08857 NM_001289908 NM_001289909 NM_001289911 NM_001371074 NM_001371075 NM_001371077 NM_001371078 NM_001371079 NM_001371080 NM_001371081 NM_001159555 NM_001159556 NM_001159557 NM_001159558 NM_007643 NP_001276837 NP_001276838 NP_001276840 NP_001358003 NP_001358004 NP_001358006 NP_001358007 NP_001358008 NP_001358009 NP_001358010 NP_001153027 NP_001153028 NP_001153029 NP_001153030 NP_031669 CD36 ( cluster of differentiation 36), also known as platelet glycoprotein 4 , fatty acid translocase ( FAT ), scavenger receptor class B member 3 ( SCARB3 ), and glycoproteins 88 ( GP88 ), IIIb ( GPIIIB ), or IV ( GPIV )

158-483: A Drosophila model has revealed that a member of the CD36 family is required for phagocytosis of Mycobacterium tuberculosis into macrophage phagosomes. Avirulent strains of Toxoplasma gondii bind to CD36 but virulent parasites fail to engage CD36. In mice, CD36 is required for disease tolerance but not for the development of immunity or resistance. CD36's association with the ability to taste fats has made it

237-410: A chemokine receptor on the surface of a T helper cell to gain entry. The number of CD4 and CD8 T cells in blood is often used to monitor the progression of HIV infection . While CD molecules are very useful in defining leukocytes, they are not merely markers on the cell surface . Though only a fraction of known CD molecules have been thoroughly characterised, most of them have important functions. In

316-413: A chylomicron . From within the cell, the chylomicron is released into a lymphatic capillary called a lacteal , which merges into larger lymphatic vessels. It is transported via the lymphatic system and the thoracic duct up to a location near the heart (where the arteries and veins are larger). The thoracic duct empties the chylomicrons into the bloodstream via the left subclavian vein . At this point

395-693: A fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated . Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 28. Fatty acids are a major component of the lipids (up to 70% by weight) in some species such as microalgae but in some other organisms are not found in their standalone form, but instead exist as three main classes of esters : triglycerides , phospholipids , and cholesteryl esters . In any of these forms, fatty acids are both important dietary sources of fuel for animals and important structural components for cells . The concept of fatty acid ( acide gras )

474-420: A non-opsonic receptor (the scavenger receptor CD36/ alpha-v beta-3 complex) and is involved in phagocytosis . CD36 has also been implicated in hemostasis , thrombosis , malaria , inflammation , lipid metabolism and atherogenesis . On binding a ligand the protein and ligand are internalized. This internalization is independent of macropinocytosis and occurs by an actin dependent mechanism requiring

553-471: A " CD34 +, CD31 −" cell is one that expresses CD34 but not CD31. This CD combination typically corresponds to a stem cell , as opposed to a fully differentiated endothelial cell . Some cell populations can also be defined as , , or (alternatively, , , or ), indicating an overall variability in CD expression , particularly when compared to other cells being studied. A review of the development of T cells in

632-458: A and b. Deficiency restricted to the platelets alone is known as type 2a; if CD36 is also absent from the erythroblasts the phenotype is classified as type 2b. The molecular basis is known for some cases: T1264G in both Kenyans and Gambians ; C478T (50%), 539 deletion of AC and 1159 insertion of an A, 1438-1449 deletion and a combined 839-841 deletion GAG and insertion of AAAAC in Japanese. In

711-430: A catalyst. This treatment affords saturated fatty acids. The extent of hydrogenation is indicated by the iodine number . Hydrogenated fatty acids are less prone toward rancidification . Since the saturated fatty acids are higher melting than the unsaturated precursors, the process is called hardening. Related technology is used to convert vegetable oils into margarine . The hydrogenation of triglycerides (vs fatty acids)

790-527: A cis configuration. Most fatty acids in the trans configuration ( trans fats ) are not found in nature and are the result of human processing (e.g., hydrogenation ). Some trans fatty acids also occur naturally in the milk and meat of ruminants (such as cattle and sheep). They are produced, by fermentation, in the rumen of these animals. They are also found in dairy products from milk of ruminants, and may be also found in breast milk of women who obtained them from their diet. The geometric differences between

869-417: A fuel for muscular contraction and general metabolism. Fatty acids that are required for good health but cannot be made in sufficient quantity from other substrates, and therefore must be obtained from food, are called essential fatty acids. There are two series of essential fatty acids: one has a double bond three carbon atoms away from the methyl end; the other has a double bond six carbon atoms away from

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948-500: A group of 250 black American blood donors 6 (2.4%) were found to be Naka antigen negative. CD36 deficiency may be a cause of post transfusion purpura . Below normal levels of CD36 expression in the kidneys has been implicated as a genetic risk factor for hypertension (high blood pressure). An association with myocardial fatty acid uptake in humans has been noted. The data suggest a link between hypertrophic cardiomyopathy and CD36 but this needs to be confirmed. RNAi screening in

1027-517: A higher proportion of polyunsaturated fatty acids ( DHA , omega−3 fatty acid ) than reptiles . Studies on bird fatty acid composition have noted similar proportions to mammals but with 1/3rd less omega−3 fatty acids as compared to omega−6 for a given body size. This fatty acid composition results in a more fluid cell membrane but also one that is permeable to various ions ( H & Na ), resulting in cell membranes that are more costly to maintain. This maintenance cost has been argued to be one of

1106-487: A hydrophobic pocket shared by several CD36 ligands, e.g. fatty acid and oxLDL. Recent research concluded that CD36 is involved in the fat taste transduction ( oleogustus ). Infections with the human malaria parasite Plasmodium falciparum are characterized by sequestration of erythrocytes infected with mature forms of the parasite and CD36 has been shown to be a major sequestration receptor on microvascular endothelial cells. Parasitised erythrocytes adhere to endothelium at

1185-475: A p K a of 4.96, being only slightly weaker than acetic acid (4.76). As the chain length increases, the solubility of the fatty acids in water decreases, so that the longer-chain fatty acids have minimal effect on the pH of an aqueous solution. Near neutral pH, fatty acids exist at their conjugate bases, i.e. oleate, etc. Solutions of fatty acids in ethanol can be titrated with sodium hydroxide solution using phenolphthalein as an indicator. This analysis

1264-409: A predicted molecular weight of approximately 53,000 Da . However, CD36 is extensively glycosylated and has an apparent molecular weight of 88,000 Da as determined by SDS polyacrylamide gel electrophoresis . Using Kyte–Doolittle analysis , the amino acid sequence of CD36 predicts a hydrophobic region near each end of the protein large enough to span cellular membranes . Based on this notion and

1343-471: A role for CD36 in fatty acid metabolism, heart disease , taste, and dietary fat processing in the intestine . It may be involved in glucose intolerance, atherosclerosis , arterial hypertension , diabetes , cardiomyopathy , Alzheimer's disease and various cancers , mostly of epithelial origin ( breast , prostate , ovary , and colon ) and also for hepatic carcinoma and gliomas . In humans , rats and mice , CD36 consists of 472 amino acids with

1422-532: A role in the innate immune response to malaria in mouse models. Compared with wild type mice CD36 (-/-) mice the cytokine induction response and parasite clearance were impaired. Earlier peak parasitemias, higher parasite densities and higher mortality were noted. It is thought that CD36 is involved in the Plasmodium falciparum glycophosphatidylinositol (PfGPI) induced MAPK activation and proinflammatory cytokine secretion. When macrophages were exposed to PfGPI

1501-431: A small degree because they contain antioxidants, such as tocopherol . Fats and oils often are treated with chelating agents such as citric acid to remove the metal catalysts. Unsaturated fatty acids are susceptible to degradation by ozone. This reaction is practiced in the production of azelaic acid ((CH 2 ) 7 (CO 2 H) 2 ) from oleic acid . Short- and medium-chain fatty acids are absorbed directly into

1580-489: A study of 827 apparently healthy Japanese volunteers, type I and II deficiencies were found in 8 (1.0%) and 48 (5.8%) respectively. In 1127 healthy French blood donors (almost all of whom were white Europeans) no CD36 deficiency was found. In a second group only 1 of 301 white test subjects was found to be CD36 deficient. 16 of the 206 sub-Saharan black Africans and 1 of 148 black Caribbeans were found to be CD36 -ve. Three of 13 CD36 -ve persons examined had anti CD36 antibodies. In

1659-408: A target for various studies regarding obesity and alteration of lipid tasting . CD36 mRNA expression was found to be reduced in taste bud cells (TBC) of obese sand rats ( P. obesus ) compared to lean controls, implicating an association between CD36 and obesity. Although actual levels of CD36 protein were not different between the obese and control rat cells, Abdoul-Azize et al. hypothesize that

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1738-611: A therapeutic strategy for controlling the spread of cancer. Some data from in vitro and animal studies suggested that fatty acid uptake through CD36 may promote cancer cell migration and proliferation in hepatocellular carcinoma, glioblastoma , and potentially other cancers; there was limited data from observational studies in people that low CD36 may correlate with a slightly better outcome in glioblastoma. CD36 has been shown to interact with FYN . Other human scavenger receptors related to CD36 are SCARB1 and SCARB2 proteins. Cluster of differentiation The CD nomenclature

1817-418: Is stearic acid ( n  = 16), which when neutralized with sodium hydroxide is the most common form of soap . Unsaturated fatty acids have one or more C=C double bonds . The C=C double bonds can give either cis or trans isomers. In most naturally occurring unsaturated fatty acids, each double bond has three ( n−3 ), six ( n−6 ), or nine ( n−9 ) carbon atoms after it, and all double bonds have

1896-636: Is a protein that in humans is encoded by the CD36 gene . The CD36 antigen is an integral membrane protein found on the surface of many cell types in vertebrate animals. It imports fatty acids inside cells and is a member of the class B scavenger receptor family of cell surface proteins. CD36 binds many ligands including collagen , thrombospondin , erythrocytes parasitized with Plasmodium falciparum , oxidized low density lipoprotein , native lipoproteins , oxidized phospholipids , and long-chain fatty acids . Work in genetically modified rodents suggest

1975-426: Is advantageous because the carboxylic acids degrade the nickel catalysts, affording nickel soaps. During partial hydrogenation, unsaturated fatty acids can be isomerized from cis to trans configuration. More forcing hydrogenation, i.e. using higher pressures of H 2 and higher temperatures, converts fatty acids into fatty alcohols . Fatty alcohols are, however, more easily produced from fatty acid esters . In

2054-694: Is also known as glycoprotein IV (gpIV) or glycoprotein IIIb (gpIIIb) in platelets and gives rise to the Naka antigen . The Naka null phenotype is found in 0.3% of Caucasians and appears to be asymptomatic. The null phenotype is more common in African (2.5%), Japanese , and other Asian populations (5-11%). Mutations in the human CD36 gene were first identified in a patient who, despite multiple platelet transfusions , continued to exhibit low platelet levels. This condition

2133-400: Is assigned a CD number once two specific monoclonal antibodies are shown to bind to the molecule. If the molecule has not been well characterized or has only one mAb, it is usually given the provisional indicator "w" (as in " CDw186 "). For instance, CD2 mAbs are reagents that react with a 50‐kDa transmembrane glycoprotein expressed on T cells . The CD designations were used to describe

2212-576: Is dependent on the body site the skin is covering. There are also characteristic epidermal fatty acid alterations that occur in psoriasis , atopic dermatitis , and other inflammatory conditions . The chemical analysis of fatty acids in lipids typically begins with an interesterification step that breaks down their original esters (triglycerides, waxes, phospholipids etc.) and converts them to methyl esters, which are then separated by gas chromatography or analyzed by gas chromatography and mid- infrared spectroscopy . Separation of unsaturated isomers

2291-404: Is distinctive and enables animals with a keen sense of smell to differentiate individuals. The stratum corneum – the outermost layer of the epidermis – is composed of terminally differentiated and enucleated corneocytes within a lipid matrix. Together with cholesterol and ceramides , free fatty acids form a water-impermeable barrier that prevents evaporative water loss . Generally,

2370-527: Is encoded by exon 14. The extracellular domain is encoded by the central 11 exons. Alternative splicing of the untranslated regions gives rise to at least two mRNA species. The transcription initiation site of the CD36 gene has been mapped to 289 nucleotides upstream from the translational start codon and a TATA box and several putative cis regulatory regions lie further 5'. A binding site for PEBP2/CBF factors has been identified between -158 and -90 and disruption of this site reduces expression. The gene

2449-410: Is impaired when mice are made to be obese (but not in normal weight mice), and this could be a mechanism contributing to behavior changes in the obese mice, such as decreased lipid taste sensitivity and decreased attraction to fats. There has been some investigation into human CD36 as well. A study examined oral detection of fat in obese subjects with genetic bases for high, medium, and low expression of

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2528-431: Is impervious to most free fatty acids, excluding short-chain fatty acids and medium-chain fatty acids . These cells have to manufacture their own fatty acids from carbohydrates, as described above, in order to produce and maintain the phospholipids of their cell membranes, and those of their organelles. Studies on the cell membranes of mammals and reptiles discovered that mammalian cell membranes are composed of

2607-467: Is known as refractoriness to platelet transfusion. Subsequent studies have shown that CD36 found on the surface of platelets. This antigen is recognized by the monoclonal antibodies (MAbs) OKM5 and OKM8. It is bound by the Plasmodium falciparum protein sequestrin . Depending on the nature of the mutation in codon 90 CD36 may be absent either on both platelets and monocytes (type 1) or platelets alone (type 2). Type 2 has been divided into two subtypes -

2686-493: Is known to be located on exon 5. CD36 on the surface of the platelets has been shown to be involved in adherence but direct adherence to the endothelium by the infected erythrocytes also occurs. Autoaggregation of infected erythrocytes by platelets has been shown to correlate with severe malaria and cerebral malaria in particular and antiplatelet antibodies may offer some protection. Several lines of evidence suggest that mutations in CD36 are protective against malaria: mutations in

2765-410: Is not clear what role these linkages play on the function of the mature CD36 protein on the cell surface. Besides glycosylation, additional post-translational modifications have been reported for CD36. CD36 is modified with 4 palmitoyl chains , 2 on each of the two intracellular domains. The function of these lipid modifications is currently unknown but they likely promote the association of CD36 with

2844-406: Is possible by silver ion complemented thin-layer chromatography . Other separation techniques include high-performance liquid chromatography (with short columns packed with silica gel with bonded phenylsulfonic acid groups whose hydrogen atoms have been exchanged for silver ions). The role of silver lies in its ability to form complexes with unsaturated compounds. Fatty acids are mainly used in

2923-467: Is the last letter in the Greek alphabet. A third numbering convention counts the carbons from that end, using the labels "ω", "ω−1", "ω−2". Alternatively, the label "ω− x " is written "n− x ", where the "n" is meant to represent the number of carbons in the chain. In either numbering scheme, the position of a double bond in a fatty acid chain is always specified by giving the label of the carbon closest to

3002-501: Is the numbering scheme recommended by the IUPAC . Another convention uses letters of the Greek alphabet in sequence, starting with the first carbon after the carboxyl group. Thus carbon α ( alpha ) is C-2, carbon β ( beta ) is C-3, and so forth. Although fatty acids can be of diverse lengths, in this second convention the last carbon in the chain is always labelled as ω ( omega ), which

3081-607: Is the transcriptional control of the nuclear receptor PPAR/RXR heterodimer ( Peroxisome proliferator-activated receptor – Retinoid X receptor ) and gene expression can be up regulated using synthetic and natural ligands for PPAR and RXR, including the thiazolidinedione class of anti-diabetic drugs and the vitamin A metabolite 9-cis- retinoic acid respectively. CD36 is found on platelets , erythrocytes , monocytes , differentiated adipocytes , skeletal muscle, mammary epithelial cells , spleen cells and some skin microdermal endothelial cells . The protein itself belongs to

3160-635: Is uncommon (though a few examples exist), combining markers has allowed for cell types with very specific definitions within the immune system. CD molecules are utilized in cell sorting using various methods, including flow cytometry . Two commonly used CD molecules are CD4 and CD8 , which are, in general, used as markers for helper and cytotoxic T cells, respectively. These molecules are defined in combination with CD3+, as some other leukocytes also express these CD molecules (some macrophages express low levels of CD4; dendritic cells express high levels of CD8). Human immunodeficiency virus binds CD4 and

3239-427: Is used to determine the free fatty acid content of fats; i.e., the proportion of the triglycerides that have been hydrolyzed . Neutralization of fatty acids, one form of saponification (soap-making), is a widely practiced route to metallic soaps . Hydrogenation of unsaturated fatty acids is widely practiced. Typical conditions involve 2.0–3.0 MPa of H 2 pressure, 150 °C, and nickel supported on silica as

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3318-460: The Golgi apparatus ). The "uncombined fatty acids" or "free fatty acids" found in the circulation of animals come from the breakdown (or lipolysis ) of stored triglycerides. Because they are insoluble in water, these fatty acids are transported bound to plasma albumin . The levels of "free fatty acids" in the blood are limited by the availability of albumin binding sites. They can be taken up from

3397-578: The Varrentrapp reaction certain unsaturated fatty acids are cleaved in molten alkali, a reaction which was, at one point of time, relevant to structure elucidation. Unsaturated fatty acids and their esters undergo auto-oxidation , which involves replacement of a C-H bond with C-O bond. The process requires oxygen (air) and is accelerated by the presence of traces of metals, which serve as catalysts. Doubly unsaturated fatty acids are particularly prone to this reaction. Vegetable oils resist this process to

3476-523: The carboxyl end. Thus, in an 18 carbon fatty acid, a double bond between C-12 (or ω−6) and C-13 (or ω−5) is said to be "at" position C-12 or ω−6. The IUPAC naming of the acid, such as "octadec-12-enoic acid" (or the more pronounceable variant "12-octadecanoic acid") is always based on the "C" numbering. The notation Δ is traditionally used to specify a fatty acid with double bonds at positions x , y ,.... (The capital Greek letter "Δ" ( delta ) corresponds to Roman "D", for D ouble bond). Thus, for example,

3555-519: The gene is located on the long arm of chromosome 7 at band 11.2 (7q11.2) and is encoded by 15 exons that extend over more than 32 kilobases . Both the 5' and the 3' untranslated regions contain introns : the 5' with two and the 3' one. Exons 1, 2 and first 89 nucleotides of exon 3 and as well as exon 15 are non-coding. Exon 3 contains encodes the N-terminal cytoplasmic and transmembrane domains. The C-terminal cytoplasmic and transmembrane regions

3634-485: 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 cytosol where the synthesis of fatty acids occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA, citrate (produced by

3713-437: The promoters and within introns and in exon 5 reduce the risk of severe malaria. Gene diversity studies suggest there has been positive selection on this gene presumably due to malarial selection pressure. Dissenting reports are also known suggesting that CD36 is not the sole determinant of severe malaria. In addition a role for CD36 has been found in the clearance of gametocytes (stages I and II). CD36 has been shown to have

3792-519: The thymus uses this nomenclature to identify cells transitioning from CD4 /CD8 double-positive cells to CD4 /CD8 . Since 1982 there have been nine Human Leukocyte Differentiation Antigen Workshops culminating in a conference. The CD system is commonly used as cell markers in immunophenotyping , allowing cells to be defined based on what molecules are present on their surface. These markers are often used to associate cells with certain immune functions . While using one CD molecule to define populations

3871-683: The trophozoite / schizonts stage simultaneous with the appearance of the var gene product (erythrocyte membrane protein 1) on the erythrocyte surface. The appearance of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) on the erythrocyte surface is a temperature dependent phenomenon which is due to increased protein trafficking to the erythrocyte surface at the raised temperature. PfEMP1 can bind other endothelial receptors - thrombospondin (TSP) and intercellular adhesion molecule 1 ( ICAM-1 ) – in addition to CD36 - and genes other than PfEMP1 also bind to CD36: cytoadherence linked protein (clag) and sequestrin . The PfEMP1 binding site on CD36

3950-751: The 20-carbon arachidonic acid is Δ , meaning that it has double bonds between carbons 5 and 6, 8 and 9, 11 and 12, and 14 and 15. In the context of human diet and fat metabolism, unsaturated fatty acids are often classified by the position of the double bond closest between to the ω carbon (only), even in the case of multiple double bonds such as the essential fatty acids . Thus linoleic acid (18 carbons, Δ ), γ-linole n ic acid (18-carbon, Δ ), and arachidonic acid (20-carbon, Δ ) are all classified as "ω−6" fatty acids; meaning that their formula ends with –CH=CH– CH 2 – CH 2 – CH 2 – CH 2 – CH 3 . Fatty acids with an odd number of carbon atoms are called odd-chain fatty acids , whereas

4029-407: The CD36 receptor. Those subjects with high CD36 expression were eight times more sensitive to certain fats ( oleic acid and triolein ) than the subjects with low CD36 expression. Those subjects with an intermediate amount of CD36 expression were sensitive to fat at a level between the high and low groups. This study demonstrates that there is a significant relationship between oral fat sensitivity and

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4108-608: The activation Src-family kinases, JNK and Rho-family GTPases. Unlike macropinocytosis this process is not affected by inhibitors of phosphatidylinositol 3-kinase or Na/H exchange. CD36 ligands have also been shown to promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Recently, CD36 was linked to store-operated calcium flux, phospholipase A 2 activation, and production of prostaglandin E 2 CD36 function in long-chain fatty acid uptake and signaling can be irreversibly inhibited by sulfo-N-succinimidyl oleate (SSO), which binds lysine 164 within

4187-439: The amount of CD36 receptor expression, but further investigation into CD36 could be useful for learning more about lipid tasting in the context of obesity, as CD36 may be a target for therapies in the future. Reducing the burden of senescent cells, or reducing their inflammatory secretome through CD36 neutralization, accelerates regeneration in young and old mice. CD36 plays a role in the regulation of angiogenesis , which may be

4266-423: The blood by all cells that have mitochondria (with the exception of the cells of the central nervous system ). Fatty acids can only be broken down in mitochondria, by means of beta-oxidation followed by further combustion in the citric acid cycle to CO 2 and water. Cells in the central nervous system, although they possess mitochondria, cannot take free fatty acids up from the blood, as the blood–brain barrier

4345-427: The blood circulation. They are taken in through the intestine in chylomicrons , but also exist in very low density lipoproteins (VLDL) and low density lipoproteins (LDL) after processing in the liver. In addition, when released from adipocytes , fatty acids exist in the blood as free fatty acids . It is proposed that the blend of fatty acids exuded by mammalian skin, together with lactic acid and pyruvic acid ,

4424-415: The blood via intestine capillaries and travel through the portal vein just as other absorbed nutrients do. However, long-chain fatty acids are not directly released into the intestinal capillaries. Instead they are absorbed into the fatty walls of the intestine villi and reassemble again into triglycerides . The triglycerides are coated with cholesterol and protein (protein coat) into a compound called

4503-445: The characteristic rancid odor. An analogous process happens in biodiesel with risk of part corrosion. 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

4582-652: The chylomicrons can transport the triglycerides to tissues where they are stored or metabolized for energy. Fatty acids are broken down to CO 2 and water by the intra-cellular mitochondria through beta oxidation and the citric acid cycle . In the final step ( oxidative phosphorylation ), reactions with oxygen release a lot of energy, captured in the form of large quantities of ATP . Many cell types can use either glucose or fatty acids for this purpose, but fatty acids release more energy per gram. Fatty acids (provided either by ingestion or by drawing on triglycerides stored in fatty tissues) are distributed to cells to serve as

4661-548: The class B scavenger receptor family which includes receptors for selective cholesteryl ester uptake, scavenger receptor class B type I (SR-BI) and lysosomal integral membrane protein II (LIMP-II). CD36 interacts with a number of ligands, including collagen types I and IV, thrombospondin , erythrocytes parasitized with Plasmodium falciparum , platelet-agglutinating protein p37, oxidized low density lipoprotein and long-chain fatty acids . On macrophages CD36 forms part of

4740-420: 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

4819-409: The epidermal lipid matrix is composed of an equimolar mixture of ceramides (about 50% by weight), cholesterol (25%), and free fatty acids (15%). Saturated fatty acids 16 and 18 carbons in length are the dominant types in the epidermis, while unsaturated fatty acids and saturated fatty acids of various other lengths are also present. The relative abundance of the different fatty acids in the epidermis

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4898-449: The example of CD4 and CD8, these molecules are critical in antigen recognition. Others (e.g., CD135 ) act as cell surface receptors for growth factors . Recently, the marker CD47 was found to have anti- phagocytic signals to macrophages and inhibit natural killer (NK) cells. This enabled researchers to apply CD47 as a potential target to attenuate immune rejection . Fatty acid In chemistry , particularly in biochemistry ,

4977-419: The extracellular domain of CD36 has been produced. Like SCARB2, CD36 is proposed to contain an antiparallel β-barrel core with many short α-helices adorning it. The structure is predicted to contain a hydrophobic transport tunnel. Disulfide linkages between 4 of the 6 cysteine residues in the extracellular loop are required for efficient intracellular processing and transport of CD36 to the plasma membrane . It

5056-416: The hydrocarbon chain. Most naturally occurring fatty acids have an unbranched chain of carbon atoms, with a carboxyl group (–COOH) at one end, and a methyl group (–CH3) at the other end. The position of each carbon atom in the backbone of a fatty acid is usually indicated by counting from 1 at the −COOH end. Carbon number x is often abbreviated C- x (or sometimes C x ), with x = 1, 2, 3, etc. This

5135-416: The key causes for the high metabolic rates and concomitant warm-bloodedness of mammals and birds. However polyunsaturation of cell membranes may also occur in response to chronic cold temperatures as well. In fish increasingly cold environments lead to increasingly high cell membrane content of both monounsaturated and polyunsaturated fatty acids, to maintain greater membrane fluidity (and functionality) at

5214-409: The lower temperatures . The following table gives the fatty acid, vitamin E and cholesterol composition of some common dietary fats. Fatty acids exhibit reactions like other carboxylic acids, i.e. they undergo esterification and acid-base reactions. Fatty acids do not show a great variation in their acidities, as indicated by their respective p K a . Nonanoic acid , for example, has

5293-399: The main storage form of fatty acids, and thus of energy in animals. However, fatty acids are also 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

5372-503: The membrane and possibly lipid rafts which appear to be important for some CD36 functions. CD36 could be also phosphorylated at Y62, T92, T323, ubiquitinated at K56, K469, K472 and acetylated at K52, K56, K166, K231, K394, K398, K403. In the absence of ligand, membrane bound CD36 exists primarily in a monomeric state. However exposure to the thrombospondin ligand causes CD36 to dimerize. This dimerization has been proposed to play an important role in CD36 signal transduction . In humans,

5451-707: The methyl end. Humans lack the ability to introduce double bonds in fatty acids beyond carbons 9 and 10, as counted from the carboxylic acid side. Two essential fatty acids are linoleic acid (LA) and alpha-linolenic acid (ALA). These fatty acids are widely distributed in plant oils. The human body has a limited ability to convert ALA into the longer-chain omega-3 fatty acids — eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which can also be obtained from fish. Omega−3 and omega−6 fatty acids are biosynthetic precursors to endocannabinoids with antinociceptive , anxiolytic , and neurogenic properties. Blood fatty acids adopt distinct forms in different stages in

5530-454: The observation that CD36 is found on the surface of cells, CD36 is thought to have a 'hairpin-like' structure with α-helices at the C- and N- termini projecting through the membrane and a larger extracellular loop (Fig. 1). This topology is supported by transfection experiments in cultured cells using deletion mutants of CD36. Based on the crystal structure of the homologous SCARB2 , a model of

5609-424: The physical distribution of CD36 could differ in obese rat cells. Changes in calcium mediation have been associated with CD36 and obesity as well. Taste bud cells (more specifically, cells from the circumvallate papillae ) containing CD36 that were isolated from obese mice exhibited a significantly smaller increase in calcium after fatty acid stimulation when compared to control mice: CD36 associated calcium regulation

5688-401: The proteins ERK1/2, JNK, p38, and c-Jun became phosphorylated. All these proteins are involved as secondary messengers in the immune response. These responses were blunted in the CD36 (-/-) mice. Also in the CD36 (-/-) macrophages secreted significantly less TNF-alpha on exposure to PfGPI. Work is ongoing to determine how these exactly how these responses provide protection against malaria. CD36

5767-408: The recognized molecules but had to be clarified by attaching the term antigen or molecule to the designation (e.g., CD2 molecule). Currently, "CD2" is generally used to designate the molecule, and "CD2 antibody " is used to designate the antibody. Cell populations are usually defined using a '+' or a '−' symbol to indicate whether a certain cell fraction expresses or lacks a CD molecule. For example,

5846-488: The rest are even-chain fatty acids. The difference is relevant to gluconeogenesis . The following table describes the most common systems of naming fatty acids. When circulating in the plasma (plasma fatty acids), not in their ester , fatty acids are known as non-esterified fatty acids (NEFAs) or free fatty acids (FFAs). FFAs are always bound to a transport protein , such as albumin . FFAs also form from triglyceride food oils and fats by hydrolysis, contributing to

5925-472: The saturated C15 and C17 derivatives, pentadecanoic acid and heptadecanoic acid respectively, which are found in dairy products. On a molecular level, OCFAs are biosynthesized and metabolized slightly differently from the even-chained relatives. Most common fatty acids are straight-chain compounds , with no additional carbon atoms bonded as side groups to the main hydrocarbon chain. Branched-chain fatty acids contain one or more methyl groups bonded to

6004-404: The synthesis of fatty acids. Malonyl-CoA is then involved in a repeating series of reactions that lengthens the growing fatty acid chain by two carbons at a time. Almost all natural fatty acids, therefore, have even numbers of carbon atoms. When synthesis is complete the free fatty acids are nearly always combined with glycerol (three fatty acids to one glycerol molecule) to form triglycerides ,

6083-492: The various types of unsaturated fatty acids, as well as between saturated and unsaturated fatty acids, play an important role in biological processes, and in the construction of biological structures (such as cell membranes). Most fatty acids are even-chained, e.g. stearic (C18) and oleic (C18), meaning they are composed of an even number of carbon atoms. Some fatty acids have odd numbers of carbon atoms; they are referred to as odd-chained fatty acids (OCFA). The most common OCFA are

6162-461: Was introduced in 1813 by Michel Eugène Chevreul , though he initially used some variant terms: graisse acide and acide huileux ("acid fat" and "oily acid"). Fatty acids are classified in many ways: by length, by saturation vs unsaturation, by even vs odd carbon content, and by linear vs branched. Saturated fatty acids have no C=C double bonds. They have the formula CH 3 (CH 2 ) n COOH, for different n . An important saturated fatty acid

6241-600: Was proposed and established in the 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), held in Paris in 1982. This system was intended for the classification of the many monoclonal antibodies (mAbs) generated by different laboratories around the world against epitopes on the surface molecules of leukocytes (white blood cells). Since then, its use has expanded to many other cell types, and more than 370 CD unique clusters and subclusters have been identified. The proposed surface molecule

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