Wednesday, 14 June 2017

n-Butanol (Drynariae Rhizoma) kháng U937

Effects on the Apoptosis of U937 Cell Line by n-butanol Extracts of ...

n-Butanol  (Drynariae Rhizoma) kháng U937

From Wikipedia, the free encyclopedia

  (Redirected from N-butanol)
n-Butanol
Skeletal formula of n-butanol
Spacefill model of n-butanol
Skeletal formula of n-butanol with all explicit hydrogens added
Names
Systematic IUPAC name
Butan-1-ol[1]
Other names
Butalcohol
Butanol
1-Butanol
Butyl alcohol
Butyl hydrate
Butylic alcohol
Butyralcohol
Butyric alcohol
Butyryl alcohol
n-Butyl alcohol
1-Hydroxybutane
n-Propylcarbinol
Identifiers
3D model (JSmol)
3DMetB00907
969148
ChEBI
ChemSpider
DrugBank
ECHA InfoCard100.000.683
EC Number200-751-6
25753
KEGG
MeSH1-Butanol
PubChem CID
RTECS numberEO1400000
UNII
UN number1120
Properties
C4H10O
Molar mass74.12 g·mol−1
AppearanceColourless, refractive liquid
Odorbanana-like,[2] harsh, alcoholic and sweet
Density0.81 g cm−3
Melting point−89.8 °C (−129.6 °F; 183.3 K)
Boiling point117.7 °C (243.9 °F; 390.8 K)
73 g L−1 at 25 °C
Solubilityvery soluble in acetone
miscible with ethanol, ethyl ether
log P0.839
Vapor pressure6 mmHg (20 °C)[3]
Acidity (pKa)16.10
-56.536·10−6 cm3/mol
1.3993 (20 °C)
Viscosity2.573 mPa×s (at 25 °C) [4]
1.66 D
Thermochemistry
225.7 J K−1 mol−1
−328(4) kJ mol−1
−2670(20) kJ mol−1
Hazards
Safety data sheetICSC 0111
Harmful Xn
R-phrases(outdated)R10, R22, R37/38, R41, R67
S-phrases(outdated)(S2), S7/9, S13, S26, S37/39, S46
NFPA 704
Flammability code 3: Liquids and solids that can be ignited under almost all ambient temperature conditions. Flash point between 23 and 38 °C (73 and 100 °F). E.g., gasoline)Health code 1: Exposure would cause irritation but only minor residual injury. E.g., turpentineReactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogenSpecial hazards (white): no codeNFPA 704 four-colored diamond
3
1
0
Flash point35 °C (95 °F; 308 K)
343 °C (649 °F; 616 K)
Explosive limits1.45–11.25%
Lethal dose or concentration (LD, LC):
LD50 (median dose)
790 mg/kg (rat, oral)
3484 mg/kg (rabbit, oral)
790 mg/kg (rat, oral)
1700 mg/kg (dog, oral)[5]
9221 ppm (mammal)
8000 ppm (rat, 4 hr)[5]
US health exposure limits (NIOSH):
PEL(Permissible)
TWA 100 ppm (300 mg/m3)[3]
REL(Recommended)
C 50 ppm (150 mg/m3) [skin][3]
IDLH (Immediate danger)
1400 ppm[3]
Related compounds
Related compounds
Butanethiol
n-Butylamine
Pentane
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 verify (what is Yes ?)
Infobox references
n-Butanol or n-butyl alcohol or normal butanol is a primary alcohol with a 4-carbon structure and the chemical formulaC4H9OH. Its isomers include isobutanol, 2-butanol, and tert-butanol. Butanol is one of the group of "fusel alcohols" (from the German for "bad liquor"), which have more than two carbon atoms and have significant solubility in water.
n-Butanol occurs naturally as a minor product of the fermentation of sugars and other carbohydrates,[6] and is present in many foods and beverages.[7][8] It is also a permitted artificial flavorant in the United States,[9] used in butter, cream, fruit, rum, whiskey, ice cream and ices, candy, baked goods and cordials.[10] It is also used in a wide range of consumer products.[7]
The largest use of n-butanol is as an industrial intermediate, particularly for the manufacture of butyl acetate (itself an artificial flavorant and industrial solvent). It is a petrochemical, manufactured from propylene and usually used close to the point of manufacture. Estimated production figures for 1997 are: United States 784,000 tonnes; Western Europe 575,000 tonnes; Japan 225,000 tonnes.[8]

Production[edit]

n-Butanol is produced industrially from the petrochemical feedstock propylene. Propylene is hydroformylated to butyraldehyde (oxo process) in the presence of a rhodium-based homogeneous catalyst similar to Wilkinson's catalyst. The butyraldehyde is then hydrogenated to produce n-butanol.[8]

Industrial use[edit]

n-butanol is an intermediate in the production of butyl acrylate, butyl acetate, dibutyl phthalate, dibutyl sebacate, and other butyl esters,[11][12] butyl ethers such as ethylene glycol monobutyl ether, di- and triethylene glycol monobutyl ether, and the corresponding butyl ether acetates. Other industrial uses include the manufacture of pharmaceuticals, polymers, pyroxylin plastics, herbicide esters, printing (e.g., 2,4-D, 2,4,5-T)[13] and butyl xanthate. It is also used as a diluent/reactant in the manufacture of urea–formaldehyde and melamine–formaldehyde resins.[8]

Other uses[edit]

n-Butanol is used as an ingredient in perfumes and as a solvent for the extraction of essential oils.[11] n-Butanol is also used as an extractant in the manufacture of antibiotics, hormones, and vitamins;[11][12] a solvent for paints, coatings, natural resins, gums, synthetic resins, dyes, alkaloids, and camphor.[11][12] Other miscellaneous applications of n-butanol are as a swelling agent in textiles, as a component of hydraulic brake fluids, cleaning formulations, degreasers, and repellents;[7] and as a component of ore floation agents,[13] and of wood-treating systems.[14]
n-Butanol has been proposed as a substitute for diesel fuel and gasoline. It is produced in small quantities in nearly all fermentations (see fusel oil), but species of Clostridium produce much higher yields of butanol, and research is currently underway to increase the ultimate yield of biobutanol from biomass.
The production or, in some cases, use of the following substances may result in exposure to n-butanol: artificial leather, butyl esters, rubber cement, dyes, fruit essences, lacquers, motion picture, and photographic films, raincoats, perfumes, pyroxylin plastics, rayon, safety glass, shellac varnish, and waterproofed cloth.[7]

Occurrence in nature[edit]

Honey bees use n-butanol as an Alarm pheromone.

Occurrence in food[edit]

n-Butanol occurs naturally as a result of carbohydrate fermentation in a number of alcoholic beverages, including beer,[15]grape brandies,[16] wine,[17] and whisky.[18] It has been detected in the volatiles of hops,[19] jack fruit,[20] heat-treated milks,[21] musk melon,[22] cheese,[23] southern pea seed,[24] and cooked rice.[25] n-Butanol is also formed during deep frying of corn oil, cottonseed oil, trilinolein, and triolein.[26]
n-Butanol is used as an ingredient in processed and artificial flavourings,[11] and for the extraction of lipid-free protein from egg yolk,[27] natural flavouring materials and vegetable oils, the manufacture of hop extract for beermaking, and as a solvent in removing pigments from moist curd leaf protein concentrate.[28]

Metabolism and toxicity[edit]

n-Butanol is readily absorbed through the intestinal tract and lungs, and also to some extent through the skin.[29] It is metabolized completely in vertebrates in a manner similar to ethanol: alcohol dehydrogenase converts n-butanol to butyraldehyde; this is then converted to butyric acid by aldehyde dehydrogenase. Butyric acid can be fully metabolized to carbon dioxide and water by the β-oxidation pathway. In the rat, only 0.03% of an oral dose of 2,000 mg/kg was excreted in the urine.[30]
The acute toxicity of n-butanol is relatively low, with oral LD50 values of 790–4,360 mg/kg (rat; comparable values for ethanol are 7,000–15,000 mg/kg).[8][31] No deaths were reported at an inhaled concentration of 8,000 ppm (4-hour exposure, rats). At sub-lethal doses, n-butanol acts as a depressant of the central nervous system, similar to ethanol: one study in rats indicated that the intoxicating potency of n-butanol is some six times higher than that of ethanol, possibly because of its slower transformation by alcohol dehydrogenase.[32]
n-Butanol is a natural component of many alcoholic beverages, albeit in low (but variable) concentrations.[33][34] It (along with similar fusel alcohols) is reputed to be responsible for severe "hangovers", although experiments in animal models show no evidence for this.[35] An unknown dose n-Butanol was consumed by a 47-year-old male with no previous medical history, leading to a range of adverse health effects.[clarification needed][36]

Other hazards[edit]

Liquid n-butanol, as is common with most organic solvents, is extremely irritating to the eyes; repeated contact with the skin can also cause irritation.[8] This is believed to be a generic effect of "defatting". No skin sensitization has been observed. Irritation of the respiratory pathways occurs only at very high concentrations (>2,400 ppm).[37]
With a flash point of 35 °C, n-butanol presents a moderate fire hazard: it is slightly more flammable than kerosene or diesel fuel but less flammable than many other common organic solvents. The depressant effect on the central nervous system (similar to ethanol intoxication) is a potential hazard when working with n-butanol in enclosed spaces, although the odour threshold (0.2–30 ppm) is far below the concentration which would have any neurological effect.[37][38]
n-Butanol is of low toxicity to aquatic vertebrates and invertebrates. It is rapidly biodegraded in water, although an estimated 83% partitions to air where it is degraded by hydroxyl radicals with a half-life of 1.2–2.3 days. It has low potential to bioaccumulate.[8] A potential hazard of significant discharges to watercourses is the rise in chemical oxygen demand (C.O.D.) associated with its biodegradation.
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Ceramide kháng U937

Cell-permeable ceramides act as novel regulators of U937 cell–cell ...

Ceramide kháng U937

From Wikipedia, the free encyclopedia
  (Redirected from Ceramides)

General structures of sphingolipids

Ceramide. R represents the alkyl portion of a fatty acid.
Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. Contrary to previous assumptions that ceramides and other sphingolipids found in cell membrane were purely supporting structural elements, ceramide can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells.
The word ceramide comes from the Latin cera (wax) and amide. Ceramide is a component of vernix caseosa, the waxy or cheese-like white substance found coating the skin of newborn human infants.

Pathways for ceramide synthesis[edit]

There are three major pathways of ceramide generation. The sphingomyelinase pathway uses an enzyme to break down sphingomyelin in the cell membrane and release ceramide. The de novo pathway creates ceramide from less complex molecules. Ceramide generation can also occur through breakdown of complex sphingolipids that are ultimately broken down into sphingosine, which is then reused by reacylation to form ceramide. This latter pathway is termed the Salvage pathway.

Sphingomyelin hydrolysis[edit]

Hydrolysis of sphingomyelin is catalyzed by the enzyme sphingomyelinase. Because sphingomyelin is one of the four common phospholipids found in the plasma membrane of cells, the implications of this method of generating ceramide is that the cellular membrane is the target of extracellular signals leading to programmed cell death. There has been research suggesting that when ionizing radiation causes apoptosis in some cells, the radiation leads to the activation of sphingomyelinase in the cell membrane and ultimately, to ceramide generation.[1]

De novo[edit]

De novo synthesis of ceramide begins with the condensation of palmitate and serine to form 3-keto-dihydrosphingosine. This reaction is catalyzed by the enzyme serine palmitoyl transferase and is the rate-limiting step of the pathway. In turn, 3-keto-dihydrosphingosine is reduced to dihydrosphingosine, which is then followed by acylation by the enzyme (dihydro)ceramide synthase to produce dihydroceramide. The final reaction to produce ceramide is catalyzed by dihydroceramide desaturase. De novo synthesis of ceramide occurs in the endoplasmic reticulum. Ceramide is subsequently transported to the Golgi apparatus by either vesicular trafficking or the ceramide transfer protein CERT. Once in the Golgi apparatus, ceramide can be further metabolized to other sphingolipids, such as sphingomyelin and the complex glycosphingolipids.[2]

Salvage pathway[edit]

Constitutive degradation of sphingolipids and glycosphingolipids takes place in the acidic subcellular compartments, the late endosomes and the lysosomes, with the end goal of producing sphingosine. In the case of glycosphingolipids, exohydrolases acting at acidic pH optima cause the stepwise release of monosaccharide units from the end of the oligosaccharide chains, leaving just the sphingosine portion of the molecule, which may then contribute to the generation of ceramides. Ceramide can be further hydrolyzed by acid ceramidase to form sphingosine and a free fatty acid, both of which are able to leave the lysosome, unlike ceramide. The long-chain sphingoid bases released from the lysosome may then re-enter pathways for synthesis of ceramide and/or sphingosine-1-phosphate. The salvage pathway re-utilizes long-chain sphingoid bases to form ceramide through the action of ceramide synthase. Thus, ceramide synthase family members probably trap free sphingosine released from the lysosome at the surface of the endoplasmic reticulum or in endoplasmic reticulum-associated membranes. It should also be noted that the salvage pathway has been estimated to contribute from 50% to 90% of sphingolipid biosynthesis.[3]

Physiological roles[edit]

As a bioactive lipid, ceramide has been implicated in a variety of physiological functions including apoptosis, cell growth arrest, differentiation, cell senescence, cell migration and adhesion.[2] Roles for ceramide and its downstream metabolites have also been suggested in a number of pathological states including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, and inflammation.[4][5]
Ceramides induce skeletal muscle insulin resistance when synthesized as a result of saturated fat activation of TLR4 receptors.[6] Unsaturated fat does not have this effect.[6] Ceramides induce insulin resistance in many tissues by inhibition of Akt/PKB signaling.[7] Aggregation of LDL cholesterol by ceramide causes LDL retention in arterial walls, leading to atherosclerosis.[8] Ceramides cause endothelial dysfunction by activating protein phosphatase 2 (PP2A).[9] In mitochondria, ceramide suppresses the electron transport chain and induces production of reactive oxygen species.[10]

Apoptosis[edit]

One of the most studied roles of ceramide pertains to its function as a proapoptotic molecule. Apoptosis, or Type I programmed cell death, is essential for the maintenance of normal cellular homeostasis and is an important physiological response to many forms of cellular stress. Ceramide accumulation has been found following treatment of cells with a number of apoptotic agents including ionizing radiation,[1][11] UV light,[12] TNF-alpha,[13] and chemotherapeutic agents. This suggests a role for ceramide in the biological responses of all these agents. Because of its apoptosis-inducing effects in cancer cells, ceramide has been termed the "tumor suppressor lipid". Several studies have attempted to define further the specific role of ceramide in the events of cell death and some evidence suggests ceramide functions upstream of the mitochondria in inducing apoptosis. However, owing to the conflicting and variable nature of studies into the role of ceramide in apoptosis, the mechanism by which this lipid regulates apoptosis remains elusive.[14]

Skin[edit]

Ceramide is the main component of the stratum corneum of the epidermis layer of human skin.[15][16] Together with cholesterol and saturated fatty acids, ceramide creates a water-impermeable, protective organ to prevent excessive water loss due to evaporation as well as a barrier against the entry of microorganisms.[16] In the hyperplastic disorder psoriasis the water permeability barrier is compromised.[17]
The stratum corneum is composed of 50% ceramides, 25% cholesterol, and 15% free fatty acids.[17] Key components of the extracellular lipid lamellae of the stratum corneum are ultra long chain (C28-C36) ceramides.[18] With aging there is a decline in ceramide and cholesterol in the stratum corneum of humans.[19] A clinical trial using ceramide-rich wheat extract showed increased skin hydration in those taking the extract rather than the placebo.[20]

Hormonal[edit]

Increased ceramide synthesis leads to both leptin resistance and insulin resistance by increasing SOCS-3 expression.[21] Elevated level of ceramide results in the inhibition of insulin signal transduction pathway and the serine phosphorylation of JNK, leading to insulin resistance.[22]

Substances known to induce ceramide generation[edit]

Mechanism by which ceramide signaling occurs[edit]

Currently, the means by which ceramide acts as a signaling molecule are not clear.
One hypothesis is that ceramide generated in the plasma membrane enhances membrane rigidity and stabilizes smaller lipid platforms known as lipid rafts, allowing them to serve as platforms for signalling molecules. Moreover, as rafts on one leaflet of the membrane can induce localized changes in the other leaflet of the bilayer, they can potentially serve as the link between signals from outside the cell to signals to be generated within the cell.
Ceramide has also been shown to form organized large channels traversing the mitochondrial outer membrane. This leads to the egress of proteins from the intermembrane space.[26][27][28]

Uses[edit]

Ceramides may be found as ingredients of some topical skin medications used to complement treatment for skin conditions such as eczema.[29] They are also used in cosmetic products such as some soaps, shampoos, skin creams, and sunscreens.[30] Additionally, ceramides are being explored as a potential therapeutic in cancer.[31]
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