Misplaced Pages

#820179

90-505: Lipoproteins transfer lipids ( fats ) around the body in the extracellular fluid , making fats available to body cells for receptor-mediated endocytosis . Lipoproteins are complex particles composed of multiple proteins , typically 80–100 proteins per particle (organized by a single apolipoprotein B for LDL and the larger particles). A single LDL particle is about 220–275 angstroms in diameter, typically transporting 3,000 to 6,000 fat molecules per particle, and varying in size according to

180-422: A 12 to 14 h fast and that LDL-C cannot be calculated if plasma triglyceride is >4.52 mmol/L (400 mg/dL). Even at triglyceride levels 2.5 to 4.5 mmol/L, this formula is considered inaccurate. If both total cholesterol and triglyceride levels are elevated then a modified formula, with quantities in mg/dL, may be used This formula provides an approximation with fair accuracy for most people, assuming

270-535: A century, chemists regarded "fats" as only simple lipids made of fatty acids and glycerol (glycerides), but new forms were described later. Theodore Gobley (1847) discovered phospholipids in mammalian brain and hen egg, called by him as " lecithins ". Thudichum discovered in human brain some phospholipids ( cephalin ), glycolipids ( cerebroside ) and sphingolipids ( sphingomyelin ). The terms lipoid, lipin, lipide and lipid have been used with varied meanings from author to author. In 1912, Rosenbloom and Gies proposed

360-408: A complicated family of compounds that share a common structural feature, a sphingoid base backbone that is synthesized de novo from the amino acid serine and a long-chain fatty acyl CoA, then converted into ceramides , phosphosphingolipids, glycosphingolipids and other compounds. The major sphingoid base of mammals is commonly referred to as sphingosine . Ceramides (N-acyl-sphingoid bases) are

450-415: A cycle of reactions that add the acetyl group, reduce it to an alcohol, dehydrate it to an alkene group and then reduce it again to an alkane group. The enzymes of fatty acid biosynthesis are divided into two groups, in animals and fungi all these fatty acid synthase reactions are carried out by a single multifunctional protein, while in plant plastids and bacteria separate enzymes perform each step in

540-417: A diverse family of molecules composed of one or more sugar residues linked via a glycosidic bond to the sphingoid base. Examples of these are the simple and complex glycosphingolipids such as cerebrosides and gangliosides . Sterols, such as cholesterol and its derivatives, are an important component of membrane lipids, along with the glycerophospholipids and sphingomyelins. Other examples of sterols are

630-425: A dynamic lipid-bilayer matrix as revealed by magnetic resonance and electron microscope studies. A biological membrane is a form of lamellar phase lipid bilayer . The formation of lipid bilayers is an energetically preferred process when the glycerophospholipids described above are in an aqueous environment. This is known as the hydrophobic effect . In an aqueous system, the polar heads of lipids align towards

720-644: A fatty acid contains a double bond, there is the possibility of either a cis or trans geometric isomerism , which significantly affects the molecule's configuration . Cis -double bonds cause the fatty acid chain to bend, an effect that is compounded with more double bonds in the chain. Three double bonds in 18-carbon linolenic acid , the most abundant fatty-acyl chains of plant thylakoid membranes , render these membranes highly fluid despite environmental low-temperatures, and also makes linolenic acid give dominating sharp peaks in high resolution 13-C NMR spectra of chloroplasts. This in turn plays an important role in

810-467: A general term for LDL particles with oxidatively modified structural components. As a result, from free radical attack, both lipid and protein parts of LDL can be oxidized in the vascular wall. Besides the oxidative reactions taking place in vascular wall, oxidized lipids in LDL can also be derived from oxidized dietary lipids. Oxidized LDL is known to associate with the development of atherosclerosis , and it

900-471: A glycerol core linked to two fatty acid-derived "tails" by ester linkages and to one "head" group by a phosphate ester linkage. While glycerophospholipids are the major component of biological membranes, other non-glyceride lipid components such as sphingomyelin and sterols (mainly cholesterol in animal cell membranes) are also found in biological membranes. In plants and algae, the galactosyldiacylglycerols, and sulfoquinovosyldiacylglycerol, which lack

990-445: A higher proportion of cholesterol esters. When a cell requires additional cholesterol (beyond its current internal HMGCoA production pathway), it synthesizes the necessary LDL receptors as well as PCSK9 , a proprotein convertase that marks the LDL receptor for degradation. LDL receptors are inserted into the plasma membrane and diffuse freely until they associate with clathrin -coated pits. When LDL receptors bind LDL particles in

SECTION 10

#1732771880821

1080-525: A higher risk for coronary heart disease . This is thought to be because the smaller particles are more easily able to penetrate the endothelium of arterial walls . Pattern I , for intermediate , indicates that most LDL particles are very close in size to the normal gaps in the endothelium (26 nm). According to one study, sizes 19.0–20.5 nm were designated as pattern B and LDL sizes 20.6–22 nm were designated as pattern A. Other studies have shown no such correlation at all. Some evidence suggests

1170-520: A lesser extent size, have shown slightly stronger correlations with atherosclerotic progression and cardiovascular events than obtained using chemical measures of the amount of cholesterol carried by the LDL particles. It is possible that the LDL cholesterol concentration can be low, yet LDL particle number high and cardiovascular events rates are high. Correspondingly, it is possible that LDL cholesterol concentration can be relatively high, yet LDL particle number low and cardiovascular events are also low. In

1260-457: A major subclass of sphingoid base derivatives with an amide -linked fatty acid. The fatty acids are typically saturated or mono-unsaturated with chain lengths from 16 to 26 carbon atoms. The major phosphosphingolipids of mammals are sphingomyelins (ceramide phosphocholines), whereas insects contain mainly ceramide phosphoethanolamines and fungi have phytoceramide phosphoinositols and mannose -containing headgroups. The glycosphingolipids are

1350-469: A phosphate group, are important components of membranes of chloroplasts and related organelles and are among the most abundant lipids in photosynthetic tissues, including those of higher plants, algae and certain bacteria. Plant thylakoid membranes have the largest lipid component of a non-bilayer forming monogalactosyl diglyceride (MGDG), and little phospholipids; despite this unique lipid composition, chloroplast thylakoid membranes have been shown to contain

1440-538: A primary component of cellular membranes and binding sites for intra- and intercellular proteins, some glycerophospholipids in eukaryotic cells, such as phosphatidylinositols and phosphatidic acids are either precursors of or, themselves, membrane-derived second messengers . Typically, one or both of these hydroxyl groups are acylated with long-chain fatty acids, but there are also alkyl-linked and 1Z-alkenyl-linked ( plasmalogen ) glycerophospholipids, as well as dialkylether variants in archaebacteria. Sphingolipids are

1530-635: A process called fatty acid synthesis . They are made of a hydrocarbon chain that terminates with a carboxylic acid group; this arrangement confers the molecule with a polar , hydrophilic end, and a nonpolar, hydrophobic end that is insoluble in water. The fatty acid structure is one of the most fundamental categories of biological lipids and is commonly used as a building-block of more structurally complex lipids. The carbon chain, typically between four and 24 carbons long, may be saturated or unsaturated , and may be attached to functional groups containing oxygen , halogens , nitrogen , and sulfur . If

1620-421: A quinonoid core of non-isoprenoid origin. Vitamin E and vitamin K , as well as the ubiquinones , are examples of this class. Prokaryotes synthesize polyprenols (called bactoprenols ) in which the terminal isoprenoid unit attached to oxygen remains unsaturated, whereas in animal polyprenols ( dolichols ) the terminal isoprenoid is reduced. Saccharolipids describe compounds in which fatty acids are linked to

1710-456: A risk factor for cardiovascular disease . Fats that are good for one may be turned into trans fats by improper cooking methods that result in overcooking the lipids. A few studies have suggested that total dietary fat intake is linked to an increased risk of obesity. and diabetes; Others, including the Women's Health Initiative Dietary Modification Trial, an eight-year study of 49,000 women,

1800-690: A sugar backbone, forming structures that are compatible with membrane bilayers. In the saccharolipids, a monosaccharide substitutes for the glycerol backbone present in glycerolipids and glycerophospholipids. The most familiar saccharolipids are the acylated glucosamine precursors of the Lipid ;A component of the lipopolysaccharides in Gram-negative bacteria . Typical lipid A molecules are disaccharides of glucosamine, which are derivatized with as many as seven fatty-acyl chains. The minimal lipopolysaccharide required for growth in E. coli

1890-407: Is steroid biosynthesis . Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol . Lanosterol can then be converted into other steroids such as cholesterol and ergosterol. Beta oxidation is the metabolic process by which fatty acids are broken down in the mitochondria or in peroxisomes to generate acetyl-CoA . For

SECTION 20

#1732771880821

1980-926: Is Kdo 2 -Lipid A, a hexa-acylated disaccharide of glucosamine that is glycosylated with two 3-deoxy-D-manno-octulosonic acid (Kdo) residues. Polyketides are synthesized by polymerization of acetyl and propionyl subunits by classic enzymes as well as iterative and multimodular enzymes that share mechanistic features with the fatty acid synthases . They comprise many secondary metabolites and natural products from animal, plant, bacterial, fungal and marine sources, and have great structural diversity. Many polyketides are cyclic molecules whose backbones are often further modified by glycosylation , methylation , hydroxylation , oxidation , or other processes. Many commonly used antimicrobial , antiparasitic , and anticancer agents are polyketides or polyketide derivatives, such as erythromycins , tetracyclines , avermectins , and antitumor epothilones . Eukaryotic cells feature

2070-464: Is a vital part of the cell signaling . Lipid signaling may occur via activation of G protein-coupled or nuclear receptors , and members of several different lipid categories have been identified as signaling molecules and cellular messengers . These include sphingosine-1-phosphate , a sphingolipid derived from ceramide that is a potent messenger molecule involved in regulating calcium mobilization, cell growth, and apoptosis; diacylglycerol and

2160-419: 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

2250-455: Is always one-fifth of the triglyceride concentration. Another formulae addresses this issue by using an adjustable factor or by using a regression equation. There are few studies which have compared the LDL-C values derived from this formula and values obtained by direct enzymatic method. Direct enzymatic method are found to be accurate and it has to be the test of choice in clinical situations. In

2340-523: Is always pronounced (ɪd). In 1947, T. P. Hilditch defined "simple lipids" as greases and waxes (true waxes, sterols, alcohols). Lipids have been classified into eight categories by the Lipid MAPS consortium as follows: Fatty acyls, a generic term for describing fatty acids, their conjugates and derivatives, are a diverse group of molecules synthesized by chain-elongation of an acetyl-CoA primer with malonyl-CoA or methylmalonyl-CoA groups in

2430-416: Is an area of study within biophysics . Micelles and bilayers form in the polar medium by a process known as the hydrophobic effect. When dissolving a lipophilic or amphiphilic substance in a polar environment, the polar molecules (i.e., water in an aqueous solution) become more ordered around the dissolved lipophilic substance, since the polar molecules cannot form hydrogen bonds to the lipophilic areas of

2520-415: Is an oversupply of dietary carbohydrate, the excess carbohydrate is converted to triglycerides. This involves the synthesis of fatty acids from acetyl-CoA and the esterification of fatty acids in the production of triglycerides, a process called lipogenesis . Fatty acids are made by fatty acid synthases that polymerize and then reduce acetyl-CoA units. The acyl chains in the fatty acids are extended by

2610-438: Is in the form of triglycerides, cholesterol, and phospholipids. Some dietary fat is necessary to facilitate absorption of fat-soluble vitamins ( A , D , E , and K ) and carotenoids . Humans and other mammals have a dietary requirement for certain essential fatty acids, such as linoleic acid (an omega-6 fatty acid ) and alpha-linolenic acid (an omega-3 fatty acid) because they cannot be synthesized from simple precursors in

2700-400: Is surrounded by a shell of phospholipids and unesterified cholesterol, as well as the single copy of Apo B-100. LDL particles are approximately 22 nm (0.00000087 in.) to 27.5 nm in diameter and have a mass of about 3 million daltons. Since LDL particles contain a variable and changing number of fatty acid molecules, there is a distribution of LDL particle mass and size. Determining

2790-680: Is that LDL-C values are commonly discordant with both direct measurements of LDL particles and actual rates of atherosclerosis progression. Direct LDL measurements are also available and better reveal individual issues but are less often promoted or done due to slightly higher costs and being available from only a couple of laboratories in the United States . In 2008, the ADA and ACC recognized direct LDL particle measurement by NMR as superior for assessing individual risk of cardiovascular events. Chemical measures of lipid concentration have long been

Low-density lipoprotein - Misplaced Pages Continue

2880-466: Is that the NMR methodology (developed, automated & greatly reduced in costs while improving accuracy as pioneered by Jim Otvos and associates) results in a 22-25% reduction in cardiovascular events within one year, contrary to the longstanding claims by many in the medical industry that the superiority over existing methods was weak, even by statements of some proponents. Since the later 1990s, because of

2970-418: Is therefore widely studied as a potential risk factor of cardiovascular diseases . Atherogenicity of oxidized LDL has been explained by lack of recognition of oxidation-modified LDL structures by the LDL receptors, preventing the normal metabolism of LDL particles and leading eventually to development of atherosclerotic plaques. Of the lipid material contained in LDL, various lipid oxidation products are known as

3060-610: The abdominal cavity ( visceral body fat ). Visceral fat, which is more metabolically active than subcutaneous fat, has been found to produce many enzymatic signals, e.g. resistin , which increase insulin resistance and circulating VLDL particle concentrations, thus both increasing LDL particle concentrations and accelerating the development of diabetes mellitus. In 2021, scientists demonstrated that CRISPR gene editing can decrease blood levels of LDL cholesterol in Macaca fascicularis monkeys for months by 60% via knockout of PCSK9 in

3150-418: The bile acids and their conjugates, which in mammals are oxidized derivatives of cholesterol and are synthesized in the liver. The plant equivalents are the phytosterols , such as β-sitosterol , stigmasterol , and brassicasterol ; the latter compound is also used as a biomarker for algal growth. The predominant sterol in fungal cell membranes is ergosterol . Sterols are steroids in which one of

3240-470: The cannabinoid neurotransmitter anandamide . Glycerolipids are composed of mono-, di-, and tri-substituted glycerols , the best-known being the fatty acid triesters of glycerol, called triglycerides . The word "triacylglycerol" is sometimes used synonymously with "triglyceride". In these compounds, the three hydroxyl groups of glycerol are each esterified, typically by different fatty acids. Because they function as an energy store, these lipids comprise

3330-508: The carotenoids , are made by the assembly and modification of isoprene units donated from the reactive precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate . These precursors can be made in different ways. In animals and archaea , the mevalonate pathway produces these compounds from acetyl-CoA, while in plants and bacteria the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates. One important reaction that uses these activated isoprene donors

3420-403: The citric acid cycle and the electron transport chain . Hence the citric acid cycle can start at acetyl-CoA when fat is being broken down for energy if there is little or no glucose available. The energy yield of the complete oxidation of the fatty acid palmitate is 106 ATP. Unsaturated and odd-chain fatty acids require additional enzymatic steps for degradation. Most of the fat found in food

3510-790: The cosmetic and food industries , and in nanotechnology . Lipids may be broadly defined as hydrophobic or amphiphilic small molecules; the amphiphilic nature of some lipids allows them to form structures such as vesicles , multilamellar/ unilamellar liposomes , or membranes in an aqueous environment. Biological lipids originate entirely or in part from two distinct types of biochemical subunits or "building-blocks": ketoacyl and isoprene groups. Using this approach, lipids may be divided into eight categories: fatty acyls , glycerolipids , glycerophospholipids , sphingolipids , saccharolipids , and polyketides (derived from condensation of ketoacyl subunits); and sterol lipids and prenol lipids (derived from condensation of isoprene subunits). Although

3600-399: The liver . Lipid Lipids are a broad group of organic compounds which include fats , waxes , sterols , fat-soluble vitamins (such as vitamins A , D , E and K ), monoglycerides , diglycerides , phospholipids , and others. The functions of lipids include storing energy, signaling , and acting as structural components of cell membranes . Lipids have applications in

3690-548: The phosphatidylinositol phosphates (PIPs), involved in calcium-mediated activation of protein kinase C ; the prostaglandins , which are one type of fatty-acid derived eicosanoid involved in inflammation and immunity ; the steroid hormones such as estrogen , testosterone and cortisol , which modulate a host of functions such as reproduction, metabolism and blood pressure; and the oxysterols such as 25-hydroxy-cholesterol that are liver X receptor agonists . Phosphatidylserine lipids are known to be involved in signaling for

Low-density lipoprotein - Misplaced Pages Continue

3780-480: The progestogens as well as the glucocorticoids and mineralocorticoids . The secosteroids , comprising various forms of vitamin D , are characterized by cleavage of the B ring of the core structure. Prenol lipids are synthesized from the five-carbon-unit precursors isopentenyl diphosphate and dimethylallyl diphosphate , which are produced mainly via the mevalonic acid (MVA) pathway. The simple isoprenoids (linear alcohols, diphosphates, etc.) are formed by

3870-435: The 2004 updated American Heart Association, NIH and NCEP recommendations are for LDL levels to be lowered to less than 70 mg/dL. This low level of less than 70 mg/dL was recommended for primary prevention of 'very-high risk patients' and in secondary prevention as a 'reasonable further reduction'. This position was disputed. Statin drugs involved in such clinical trials have numerous physiological effects beyond simply

3960-560: The Nurses' Health Study, and the Health Professionals Follow-up Study, revealed no such links. None of these studies suggested any connection between percentage of calories from fat and risk of cancer, heart disease, or weight gain. The Nutrition Source, a website maintained by the department of nutrition at the T. H. Chan School of Public Health at Harvard University , summarizes the current evidence on

4050-787: The US, the American Heart Association , NIH , and NCEP provide a set of guidelines for fasting LDL-Cholesterol levels, estimated or measured, and risk for heart disease. As of about 2005, these guidelines were: Over time, with more clinical research, these recommended levels keep being reduced because LDL reduction, including to abnormally low levels, was the most effective strategy for reducing cardiovascular death rates in one large double blind , randomized clinical trial of men with hypercholesterolemia ; far more effective than coronary angioplasty/stenting or bypass surgery. For instance, for people with known atherosclerosis diseases,

4140-599: The accurate approach. A study was conducted measuring the effects of guideline changes on LDL cholesterol reporting and control for diabetes visits in the US from 1995 to 2004. It was found that although LDL cholesterol reporting and control for diabetes and coronary heart disease visits improved continuously between 1995 and 2004, neither the 1998 ADA guidelines nor the 2001 ATP III guidelines increased LDL cholesterol control for diabetes relative to coronary heart disease. There are several competing methods for measurement of lipoprotein particle concentrations and size. The evidence

4230-568: The amphiphile. So in an aqueous environment, the water molecules form an ordered " clathrate " cage around the dissolved lipophilic molecule. The formation of lipids into protocell membranes represents a key step in models of abiogenesis , the origin of life. Triglycerides, stored in adipose tissue, are a major form of energy storage both in animals and plants. They are a major source of energy in aerobic respiration. The complete oxidation of fatty acids releases about 38 kJ/g (9  kcal/g ), compared with only 17 kJ/g (4 kcal/g) for

4320-424: The blood was drawn after fasting for about 14 hours or longer, but does not reveal the actual LDL particle concentration because the percentage of fat molecules within the LDL particles which are cholesterol varies, as much as 8:1 variation. There are several formulas published addressing the inaccuracy in LDL-C estimation. The inaccuracy is based on the assumption that VLDL-C (Very low density lipoprotein cholesterol)

4410-414: The bloodstream, the clathrin-coated pits are endocytosed into the cell. Vesicles containing LDL receptors bound to LDL are delivered to the endosome . In the presence of low pH , such as that found in the endosome, LDL receptors undergo a conformation change, releasing LDL. LDL is then shipped to the lysosome , where cholesterol esters in the LDL are hydrolysed . LDL receptors are typically returned to

4500-644: The brain) contains relatively high amounts of glycerophospholipids, and alterations in their composition has been implicated in various neurological disorders. Glycerophospholipids may be subdivided into distinct classes, based on the nature of the polar headgroup at the sn -3 position of the glycerol backbone in eukaryotes and eubacteria, or the sn -1 position in the case of archaebacteria . Examples of glycerophospholipids found in biological membranes are phosphatidylcholine (also known as PC, GPCho or lecithin ), phosphatidylethanolamine (PE or GPEtn) and phosphatidylserine (PS or GPSer). In addition to serving as

4590-450: The bulk of storage fat in animal tissues. The hydrolysis of the ester bonds of triglycerides and the release of glycerol and fatty acids from adipose tissue are the initial steps in metabolizing fat. Additional subclasses of glycerolipids are represented by glycosylglycerols, which are characterized by the presence of one or more sugar residues attached to glycerol via a glycosidic linkage . Examples of structures in this category are

SECTION 50

#1732771880821

4680-485: The cells or cell fragments exposing them. The "fat-soluble" vitamins ( A , D , E and K ) – which are isoprene -based lipids – are essential nutrients stored in the liver and fatty tissues, with a diverse range of functions. Acyl-carnitines are involved in the transport and metabolism of fatty acids in and out of mitochondria, where they undergo beta oxidation . Polyprenols and their phosphorylated derivatives also play important transport roles, in this case

4770-551: The cholesterol production pathway, and is present in every animal cell. LDL-C is not a measurement of actual LDL particles. LDL-C is only an estimate (not measured from the individual's blood sample) of how much cholesterol is being transported by all LDL particles, which is either a smaller concentration of large particles or a high concentration of small particles. LDL particles carry many fat molecules (typically 3,000 to 6,000 fat molecules per LDL particle); this includes cholesterol, triglycerides, phospholipids and others. Thus even if

4860-513: The compartmentalized membrane-bound organelles that carry out different biological functions. The glycerophospholipids are the main structural component of biological membranes , as the cellular plasma membrane and the intracellular membranes of organelles; in animal cells, the plasma membrane physically separates the intracellular components from the extracellular environment. The glycerophospholipids are amphipathic molecules (containing both hydrophobic and hydrophilic regions) that contain

4950-501: The concept not only the traditional fats (glycerides), but also the "lipoids", with a complex constitution. The word lipide was unanimously approved by the international commission of the Société de Chimie Biologique during the plenary session on July 3, 1923. The word lipide was later anglicized as lipid because of its pronunciation ('lɪpɪd). In French, the suffix -ide , from Ancient Greek -ίδης (meaning 'son of' or 'descendant of'),

5040-506: The correlation between Pattern B and coronary heart disease is stronger than the correspondence between the LDL number measured in the standard lipid profile test. Tests to measure these LDL subtype patterns have been more expensive and not widely available, so the common lipid profile test is used more often. There has also been noted a correspondence between higher triglyceride levels and higher levels of smaller, denser LDL particles and alternately lower triglyceride levels and higher levels of

5130-401: The development of NMR measurements, it has been possible to clinically measure lipoprotein particles at lower cost [under $ 80 US (including shipping) & is decreasing; versus the previous costs of >$ 400 to >$ 5,000] and higher accuracy. There are two other assays for LDL particles, however, like LDL-C, most only estimate LDL particle concentrations. Direct LDL particle measurement by NMR

5220-424: The diet. Both of these fatty acids are 18-carbon polyunsaturated fatty acids differing in the number and position of the double bonds. Most vegetable oils are rich in linoleic acid ( safflower , sunflower , and corn oils). Alpha-linolenic acid is found in the green leaves of plants and in some seeds, nuts, and legumes (in particular flax , rapeseed , walnut , and soy ). Fish oils are particularly rich in

5310-486: The diet. In 1815, Henri Braconnot classified lipids ( graisses ) in two categories, suifs (solid greases or tallow) and huiles (fluid oils). In 1823, Michel Eugène Chevreul developed a more detailed classification, including oils, greases, tallow, waxes, resins, balsams and volatile oils (or essential oils). The first synthetic triglyceride was reported by Théophile-Jules Pelouze in 1844, when he produced tributyrin by treating butyric acid with glycerin in

5400-403: The digalactosyldiacylglycerols found in plant membranes and seminolipid from mammalian sperm cells . Glycerophospholipids, usually referred to as phospholipids (though sphingomyelins are also classified as phospholipids), are ubiquitous in nature and are key components of the lipid bilayer of cells, as well as being involved in metabolism and cell signaling . Neural tissue (including

5490-661: The fatty acids being carried, enabling these fats to move around the body within the water outside cells. Each particle contains a single apolipoprotein B-100 molecule ( Apo B-100 , a protein that has 4536 amino acid residues and a mass of 514 kDa ), along with 80 to 100 additional ancillary proteins. Each LDL has a highly hydrophobic core consisting of polyunsaturated fatty acid known as linoleate and hundreds to thousands (about 1500 commonly cited as an average) of esterified and unesterified cholesterol molecules. This core also carries varying numbers of triglycerides and other fats and

SECTION 60

#1732771880821

5580-444: The form of partially hydrogenated oils) has been banned in the US since 2021. However, trans fat can still be found in red meat and dairy products as it is produced in small amounts by ruminants such as sheep and cows. LDL cholesterol can also be lowered by increasing consumption of soluble fiber and plant-based foods. Another lifestyle approach to reduce LDL cholesterol has been minimizing total body fat, in particular fat stored inside

5670-474: The hundreds to thousands of cholesterol molecules within an average LDL particle were measured, this does not reflect the other fat molecules or even the number of LDL particles. LDL cholesterol can be lowered by through dietary intervention by limiting foods with saturated fat and avoiding foods with trans fat . Saturated fats are found in meat products (including poultry), full-fat dairy, eggs, and refined tropical oils like coconut and palm. Added trans fat (in

5760-483: The hydrogen atoms is substituted with a hydroxyl group , at position 3 in the carbon chain. They have in common with steroids the same fused four-ring core structure. Steroids have different biological roles as hormones and signaling molecules . The eighteen-carbon (C18) steroids include the estrogen family whereas the C19 steroids comprise the androgens such as testosterone and androsterone . The C21 subclass includes

5850-482: The inner mitochondrial membrane. They are believed to activate enzymes involved with oxidative phosphorylation . Lipids also form the basis of steroid hormones. The major dietary lipids for humans and other animals are animal and plant triglycerides, sterols, and membrane phospholipids. The process of lipid metabolism synthesizes and degrades the lipid stores and produces the structural and functional lipids characteristic of individual tissues. In animals, when there

5940-400: The larger, less dense ("buoyant") LDL. With continued research, decreasing cost, greater availability and wider acceptance of other lipoprotein subclass analysis assay methods, including NMR spectroscopy , research studies have continued to show a stronger correlation between human clinically obvious cardiovascular events and quantitatively measured particle concentrations. Oxidized LDL is

6030-501: The longer-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid . Many studies have shown positive health benefits associated with consumption of omega-3 fatty acids on infant development, cancer, cardiovascular diseases, and various mental illnesses (such as depression, attention-deficit hyperactivity disorder, and dementia). In contrast, it is now well-established that consumption of trans fats , such as those present in partially hydrogenated vegetable oils , are

6120-468: The most part, fatty acids are oxidized by a mechanism that is similar to, but not identical with, a reversal of the process of fatty acid synthesis. That is, two-carbon fragments are removed sequentially from the carboxyl end of the acid after steps of dehydrogenation , hydration , and oxidation to form a beta-keto acid , which is split by thiolysis . The acetyl-CoA is then ultimately converted into adenosine triphosphate (ATP), CO 2 , and H 2 O using

6210-572: The most-used clinical measurement, not because they have the best correlation with individual outcome, but because these lab methods are less expensive and more widely available. The lipid profile does not measure LDL particles. It only estimates them using the Friedewald equation by subtracting the amount of cholesterol associated with other particles, such as HDL and VLDL, assuming a prolonged fasting state, etc.: There are limitations to this method, most notably that samples must be obtained after

6300-518: The number and mix of fat molecules contained within. The lipids carried include all fat molecules with cholesterol , phospholipids , and triglycerides dominant; amounts of each vary considerably. A good clinical interpretation of blood lipid levels is that high LDL, in combination with a high amount of triglycerides, which indicates a high likelihood of the LDL being oxidised, is associated with increased risk of cardiovascular diseases . Each native LDL particle enables emulsification, i.e. surrounding

6390-414: The oxidative breakdown of carbohydrates and proteins . The adipocyte , or fat cell, is designed for continuous synthesis and breakdown of triglycerides in animals, with breakdown controlled mainly by the activation of hormone-sensitive enzyme lipase . Migratory birds that must fly long distances without eating use triglycerides to fuel their flights. Evidence has emerged showing that lipid signaling

6480-460: The pathway. The fatty acids may be subsequently converted to triglycerides that are packaged in lipoproteins and secreted from the liver. The synthesis of unsaturated fatty acids involves a desaturation reaction, whereby a double bond is introduced into the fatty acyl chain. For example, in humans, the desaturation of stearic acid by stearoyl-CoA desaturase-1 produces oleic acid . The doubly unsaturated fatty acid linoleic acid as well as

6570-681: The people participating and being tracked in the MESA trial , a medical research study sponsored by the United States National Heart, Lung, and Blood Institute. The lowest incidence of atherosclerotic events over time occurs within the <20% group, with increased rates for the higher groups. Multiple other measures, including particle sizes, small LDL particle concentrations, large total and HDL particle concentrations, along with estimations of insulin resistance pattern and standard cholesterol lipid measurements (for comparison of

6660-400: The phagocytosis of apoptotic cells or pieces of cells. They accomplish this by being exposed to the extracellular face of the cell membrane after the inactivation of flippases which place them exclusively on the cytosolic side and the activation of scramblases, which scramble the orientation of the phospholipids. After this occurs, other cells recognize the phosphatidylserines and phagocytosize

6750-405: The plasma data with the estimation methods discussed above) are also routinely provided. (Per 2004 United States Government Minimum Guidelines) The mevalonate pathway serves as the basis for the biosynthesis of many molecules, including cholesterol. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase ( HMG CoA reductase ) is an essential component and performs the first of 37 steps within

6840-742: The plasma membrane, where they repeat this cycle. If LDL receptors bind to PCSK9, however, transport of LDL receptors is redirected to the lysosome, where they are degraded. LDL interferes with the quorum sensing system that upregulates genes required for invasive Staphylococcus aureus infection. The mechanism of antagonism entails binding apolipoprotein B to a S. aureus autoinducer pheromone, preventing signaling through its receptor. Mice deficient in apolipoprotein B are more susceptible to invasive bacterial infection. LDL can be grouped based on its size: large low density LDL particles are described as pattern A , and small high density LDL particles are pattern B . Pattern B has been associated by some with

6930-418: The polar, aqueous environment, while the hydrophobic tails minimize their contact with water and tend to cluster together, forming a vesicle ; depending on the concentration of the lipid, this biophysical interaction may result in the formation of micelles , liposomes , or lipid bilayers . Other aggregations are also observed and form part of the polymorphism of amphiphile (lipid) behavior. Phase behavior

7020-538: The presence of concentrated sulfuric acid . Several years later, Marcellin Berthelot , one of Pelouze's students, synthesized tristearin and tripalmitin by reaction of the analogous fatty acids with glycerin in the presence of gaseous hydrogen chloride at high temperature. In 1827, William Prout recognized fat ("oily" alimentary matters), along with protein ("albuminous") and carbohydrate ("saccharine"), as an important nutrient for humans and animals. For

7110-415: The reduction of LDL levels. From longitudinal population studies following progression of atherosclerosis-related behaviors from early childhood into adulthood, the usual LDL in childhood, before the development of fatty streaks , is about 35 mg/dL. However, all the above values refer to chemical measures of lipid/cholesterol concentration within LDL, not measured low-density lipoprotein concentrations,

7200-523: The resource poor settings, the option of using the formula has to be considered. However, the concentration of LDL particles, and to a lesser extent their size, has a stronger and consistent correlation with individual clinical outcome than the amount of cholesterol within LDL particles, even if the LDL-C estimation is approximately correct. There is increasing evidence and recognition of the value of more targeted and accurate measurements of LDL particles. Specifically, LDL particle number (concentration), and to

7290-448: The structure and function of cell membranes. Most naturally occurring fatty acids are of the cis configuration, although the trans form does exist in some natural and partially hydrogenated fats and oils. 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

7380-498: The structure of LDL has been difficult for biochemists because of its heterogeneous structure. However, the structure of LDL at human body temperature in native condition, with a resolution of about 16 Angstroms using cryogenic electron microscopy , has been described in 2011. LDL particles are formed when triglycerides are removed from VLDL by the lipoprotein lipase enzyme (LPL) and they become smaller and denser (i.e. fewer fat molecules with same protein transport shell), containing

7470-481: The substitution of "lipoid" by "lipin". In 1920, Bloor introduced a new classification for "lipoids": simple lipoids (greases and waxes), compound lipoids (phospholipoids and glycolipoids), and the derived lipoids (fatty acids, alcohols , sterols). The word lipide , which stems etymologically from Greek λίπος, lipos 'fat', was introduced in 1923 by the French pharmacologist Gabriel Bertrand . Bertrand included in

7560-437: The successive addition of C5 units, and are classified according to number of these terpene units. Structures containing greater than 40 carbons are known as polyterpenes. Carotenoids are important simple isoprenoids that function as antioxidants and as precursors of vitamin A . Another biologically important class of molecules is exemplified by the quinones and hydroquinones , which contain an isoprenoid tail attached to

7650-507: The term "lipid" is sometimes used as a synonym for fats, fats are a subgroup of lipids called triglycerides . Lipids also encompass molecules such as fatty acids and their derivatives (including tri-, di-, monoglycerides, and phospholipids), as well as other sterol -containing metabolites such as cholesterol . Although humans and other mammals use various biosynthetic pathways both to break down and to synthesize lipids, some essential lipids cannot be made this way and must be obtained from

7740-646: The total LDL particle concentrations, in nmol/L plasma, are typically subdivided by percentiles referenced to the 5,382 men and women, not on any lipid medications, who are participating in the MESA trial. LDL particle concentration can also be measured by measuring the concentration of the protein ApoB, based on the generally accepted principle that each LDL or VLDL particle carries one ApoB molecule. The LDL particle concentrations are typically categorized by percentiles, <20%, 20–50%, 50th–80th%, 80th–95% and >95% groups of

7830-511: The transport of oligosaccharides across membranes. Polyprenol phosphate sugars and polyprenol diphosphate sugars function in extra-cytoplasmic glycosylation reactions, in extracellular polysaccharide biosynthesis (for instance, peptidoglycan polymerization in bacteria), and in eukaryotic protein N- glycosylation . Cardiolipins are a subclass of glycerophospholipids containing four acyl chains and three glycerol groups that are particularly abundant in

7920-422: The triply unsaturated α-linolenic acid cannot be synthesized in mammalian tissues, and are therefore essential fatty acids and must be obtained from the diet. Triglyceride synthesis takes place in the endoplasmic reticulum by metabolic pathways in which acyl groups in fatty acyl-CoAs are transferred to the hydroxyl groups of glycerol-3-phosphate and diacylglycerol. Terpenes and isoprenoids , including

8010-607: The ultimate atherogenic species. Acting as a transporter of these injurious molecules is another mechanism by which LDL can increase the risk of atherosclerosis. Blood tests commonly report LDL-C: the amount of cholesterol which is estimated to be contained with LDL particles, on average, using a formula, the Friedewald equation . In clinical context, mathematically calculated estimates of LDL-C are commonly used as an estimate of how much low density lipoproteins are driving progression of atherosclerosis. The problem with this approach

8100-689: Was mentioned by the ADA and ACC, in a 28 March 2008 joint consensus statement, as having advantages for predicting individual risk of atherosclerosis disease events, but the statement noted that the test is less widely available, is more expensive [about $ 13.00 US (2015 without insurance coverage) from some labs which use the Vantera Analyzer]. Debate continues that it is "...unclear whether LDL particle size measurements add value to measurement of LDL-particle concentration", though outcomes have always tracked LDL particle, not LDL-C, concentrations. Using NMR,

#820179