What is a fatty acid?
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Fatty acids are key components of a cell, therefore, the regulation or inhibition of fatty acid synthesis hold severe consequences for cellular function. The malfunction of the fatty acid synthesis pathway can result in cancer and obesity. However, the significance of fatty acid synthesis also make the fatty acid synthesis pathway a potential target for the search and study of anticancer and antibiotic drugs. It has been found that in humans, fatty acid synthase, is overly expressed in cancer cells. Therefore, FAS, which has been associated only with energy production prior, is now associated with aggressive tumor growth and survival. Studies have also found that human fatty acid synthase is overly expressed in prostate cancer cells.
Fatty-acyl-CoA synthase
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In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with a long 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 usually not found in organisms, but instead as three main classes of esters: triglycerides, phospholipids, and cholesterol esters. In any of these forms, fatty acids are both important dietary sources of fuel for animals and they are important structural components for cells.
Fatty acid
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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, 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 the Golgi apparatus).
Fatty acid
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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 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 and water. Cells in the central nervous system, which, although they possess mitochondria, cannot take free fatty acids up from the blood, as the blood-brain barrier 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.
Fatty acid
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Examples of biologically important fatty acids include the eicosanoids, derived primarily from arachidonic acid and eicosapentaenoic acid, that include prostaglandins, leukotrienes, and thromboxanes. Docosahexaenoic acid is also important in biological systems, particularly with respect to sight. Other major lipid classes in the fatty acid category are the fatty esters and fatty amides. Fatty esters include important biochemical intermediates such as wax esters, fatty acid thioester coenzyme A derivatives, fatty acid thioester ACP derivatives and fatty acid carnitines. The fatty amides include N-acyl ethanolamines, such as the cannabinoid neurotransmitter anandamide.
Lipid
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Fatty-acyl-CoA Synthase, or more commonly known as yeast fatty acid synthase (and not to be confused with Long Chain fatty acyl-CoA synthetase), is an enzyme complex responsible for fatty acid biosynthesis, and is of Type I Fatty Acid Synthesis (FAS). Yeast fatty acid synthase plays a pivotal role in fatty acid synthesis. It is a 2.6 MDa barrel shaped complex and is composed of two, unique multi-functional subunits: alpha and beta. Together, the alpha and beta units are arranged in an αβstructure. The catalytic activities of this enzyme complex involves a coordination system of enzymatic reactions between the alpha and beta subunits. The enzyme complex therefore consists of six functional centers for fatty acid synthesis.
Fatty-acyl-CoA synthase
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Omega−3 fatty acids, also called ω−3 fatty acids or "n"−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by a double bond three atoms away from the terminal methyl group. They are widely distributed in nature, being important constituents of animal lipid metabolism, and they play an important role in the human diet and in human physiology. The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both commonly found in marine oils. Marine algae and phytoplankton are primary sources of omega−3 fatty acids. Common sources of plant oils containing ALA include walnut, edible seeds, clary sage seed oil, algal oil, flaxseed oil, Sacha Inchi oil, "Echium" oil, and hemp oil, while sources of animal omega−3 fatty acids EPA and DHA include fish, fish oils, eggs from chickens fed EPA and DHA, squid oils, and krill oil.
Omega−3 fatty acids are important for normal metabolism. Mammals are unable to synthesize omega−3 fatty acids, but can obtain the shorter-chain omega−3 fatty acid ALA (18 carbons and 3 double bonds) through diet and use it to form the more important long-chain omega−3 fatty acids, EPA (20 carbons and 5 double bonds) and then from EPA, the most crucial, DHA (22 carbons and 6 double bonds). The ability to make the longer-chain omega−3 fatty acids from ALA may be impaired in aging. In foods exposed to air, unsaturated fatty acids are vulnerable to oxidation and rancidity. Dietary supplementation with omega−3 fatty acids does not appear to affect the risk of death, cancer or heart disease. Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes or any vascular disease outcomes.
The terms "ω–3 ("omega–3") fatty acid" and "n–"3 "fatty acid" are derived from organic nomenclature. One way in which a fatty acid is named is determined by the location of the first double bond, counted from the methyl end, that is, the omega (ω-) or the "n"- end (see illustration). In general terminology using either "n–x" or ω–"x", the dash is a minus sign (although it is never read as such), and the number "n–x" (or ω–"x") refers to the locant of the double bond linking two carbon atoms. Thus, in omega"–"3 fatty acids in particular, there is a double bond located on the carbon numbered 3 lower than the highest carbon number. By example, α-linolenic acid (ALA; illustration) is an 18-carbon chain having three double bonds, the first being located at the third carbon from the methyl end of the fatty acid chain, known as the "n" end. Thus, α-linolenic acid is a polyunsaturated "n−3" (omega-3) fatty acid with lipid number, 18:3 (18 carbon atoms, 3 double bonds).
Omega-3 fatty acid
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Fatty acids do not show a great variation in their acidities, as indicated by their respective p"K". Nonanoic acid, for example, has a p"K" 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. Even those fatty acids that are insoluble in water will dissolve in warm ethanol, and can be titrated with sodium hydroxide solution using phenolphthalein as an indicator. This analysis is used to determine the free fatty acid content of fats; i.e., the proportion of the triglycerides that have been hydrolyzed.
Fatty acid
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Fatty acid synthesis is an anabolic process that starts from the conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase. Malonyl CoA leads to fatty acid synthesis (FAS) and is involved in the elongation of fatty acids through Fatty acid synthase (FASN). Although aerobic glycolysis is the best documented metabolic phenotype of tumor cells, it is not a universal feature of all human cancers. Amino acids and fatty acids have been shown to function as fuels for tumor cells to proliferate. The carnitine palmitoyltransferase enzymes that regulate the β-oxidation of fatty acids may have a key role in determining some of these phenotypes. Enhanced fatty acid synthesis provides lipids for membrane biogenesis to tumor cells and hence, it gives advantage in both growth and survival of the cell.
Tumor metabolome
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Fatty acids play an important role in normal brain development as well as maintaining proper neuronal function. It has been found that certain fatty acids that are in abundance in the brain may be linked with FFA1. These fatty acids likely activate FFA1, inducing an intracellular response. It has been found that docosahexaenoic acid (DHA) has a higher affinity than other fatty acids for FFA1. DHA makes up 30% and arachidonic acid, another fatty acid found in the brain, makes up 20% of the fatty acids in the brain. Both of these fatty acids must be obtained from the diet because the body cannot make them. A correct balance of these fatty acids is vital to normal brain function and structure. DHA is supplied to the brain via astrocytes, which release DHA so that it reaches a high enough concentration to act as an extracellular signal on FFA1.
Free fatty acid receptor 1
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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 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.
Fatty acid