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Discover the biology, biochemistry, and medical aspects of lipoproteins in this comprehensive overview of its historic and contemporary development
The fatty substance known as cholesterol is found in every cell of the human body and carries out several important functions. It is transported through the bloodstream as a part of particles called lipoproteins, which are divided into classes including low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Distinguishing between these two classes, along with the 'remnant cholesterol' particles that have recently been associated with heightened risk of heart disease and stroke, is a crucial part of managing health and developing novel pharmaceuticals.
Cholesterol, Lipoproteins, and Cardiovascular Health offers a thorough and rigorous overview of these particles, their properties, and their methods of categorization. Surveying both the characteristics of lipoproteins and their interactions with diet, lifestyle, therapeutics, and general health, it's an indispensable guide to these particles that can literally mean the difference between life and death. Cutting-edge and grounded in the latest research, it's a one-stop shop for understanding blood plasma lipoproteins in all their major forms.
Cholesterol, Lipoproteins, and Cardiovascular Health readers will also find:
Cholesterol, Lipoproteins, and Cardiovascular Health is suited for professionals, clinicians, and readers looking for a comprehensive overview of all aspects of plasma lipoproteins and their role in heart disease and stroke.
Anatol Kontush, PhD, is Research Director at Sorbonne University, and the lead author of High-Density Lipoproteins: Structure, Metabolism, Function and Therapeutics(Wiley, 2012).
Why is cholesterol a problem? Why is this substance so vital? Has this always been the case?
There are both simple and complex answers to these questions. The simple answer is that cholesterol is believed to play a crucial role in determining our lifespan. In other words, cholesterol is thought to be central to the fundamental question of life and death, which is arguably the most important question known to humankind. We believe that cholesterol is responsible for heart disease - an illness that claims more lives than any other cause. This statement may seem paradoxical when we consider that cholesterol is actually an essential substance that the human body requires for good health. How can it be that a fundamental component of the body can become harmful and even life-threatening?
Cholesterol, a type of fat, is necessary for the proper function of the body. There are biochemical pathways which aim to recycle and spare this compound.
Under normal conditions, it is a solid yellowish substance. Every cell in the body contains cholesterol. It is also an important component of lipoproteins. Animal cells produce cholesterol through a multistep complex process. By contrast, it is almost absent in bacteria.
The liver and intestines are the main sites of cholesterol production. The brain, the adrenal glands, and the reproductive organs are also sites where cholesterol is actively synthesized in humans. The brain contains a large amount of cholesterol, which accounts for about one-quarter of the total cholesterol in the human body.
Almost all cells in the body are capable of synthesizing cholesterol. Like other biological molecules, cholesterol also needs to be replaced and destroyed regularly. However, not all cells can do it. Only liver cells are able to degrade cholesterol in large quantities. Transport to the liver is necessary for continual cholesterol turnover within cells.
Cells cannot function properly without cholesterol and will die. In addition, cholesterol is used to make hormones, such as steroid hormones, stress hormones, vitamins, such as vitamin D, and bile acids that help digest food. Finally, cholesterol is important for fighting bacteria and infections.
Cholesterol is essential to separate cells from their surroundings. Cell membranes, thin structures that regulate cellular interactions with their environment, fulfill this function. Membranes are made of a material which cannot easily be destroyed by water. This kind of material is well known to everybody - it is fat. Cell membranes, which are mostly made of fat and protein, include a large amount of cholesterol.
The cholesterol in the body is a fat that is almost insoluble in water. It can also be mixed with other fats. These substances are known as lipophilic, from the Greek words "lipos," meaning "fat" and "philia," meaning "love." Up to 30% of animal cell membranes are composed of cholesterol. The fatty myelin sheath that coats neuronal cells is about one-fifth cholesterol. Communications between neuronal cells critically depend on cholesterol.
The average human body contains 35 grams (0.05%) of cholesterol, which is mostly found in the cell membranes. An average human synthesizes approximately 900 milligrams of cholesterol per day.
We all know that cholesterol can be both good and bad. These terms used by doctors around the world are familiar to us. The terms do not, however, precisely reflect the positive and negative effects of cholesterol on living organisms. As we shall see, they are derived from the measurements of cholesterol levels in blood plasma.
In the United States, a typical daily cholesterol intake is around 300 milligrams.
All animal foods are cholesterol rich, as cholesterol is synthesized in animal cells. The amount of cholesterol in food varies greatly. Cholesterol is a major component of red meat, whole eggs, and egg yolks. In addition to liver, kidneys, giblets, and fish oil, butter also contains significant quantities of cholesterol. Not negligible amounts of cholesterol are also found in human breast milk.
Cholesterol molecule consists of four carbon rings, a hydrophobic side chain and a hydrophilic hydroxyl group OH. The molecule is rigid except for the side chain. The hydroxyl group interacts with water molecules surrounding the membrane, while the side chain is stuck in the cell membrane alongside the hydrophobic chains of phospholipids. This is how cholesterol interacts and works with other lipids to regulate fluidity in cell membranes and to maintain their integrity.
Hydrophobic is derived from the Greek words for water (hydros) and fear (phobos). It means having little or no affinity for water.
Hydrophilic is derived from the Greek for water (hydros) and love (philia). It means having an affinity for water and being capable of interacting with it.
Cholesterol is a lipid. The word "lipids" comes from the Greek for fat, "lipos". Oils and fats can be considered lipids, but fats are usually solid at room temperature, while oils tend to be liquid. We attribute cholesterol to fats because it is usually solid.
Lipids make up a vital part of the human body. They are produced by the body or derived from diet. Lipids are essential for energy production, which is widespread, and are present in every cell. They form a main part of every lipoprotein particle. Lipids must be transported to their sites of use and then destroyed to produce energy. Transporting them to the required location is essential.
There are several classes of lipids.
The simplest fatty acids are chains of hydrocarbon units between the terminal hydrocarbon and carbonyl groups. Fatty acids, in the form of triglycerides, account for over 90% of the dietary fat. The bonds between the groups can be either single or double, which results in different chemical and physical properties. The more double bonds a fatty acid contains, the more fluid it is. Fatty acids that only contain single bonds between carbon atoms are less fluid, and, at physiological temperatures, can even become solid. They are called saturated fatty acids. Stearic acid, which is mostly derived from animal fats, is the most common saturated fatty acid.
Fatty acids that contain a number of double bonds are fluid and belong to oils. These fatty acids are unsaturated. Unsaturated fats are divided into monounsaturated, which have a single double-bond, and polyunsaturated with two or more. The most common monounsaturated fatty acid is oleic acid which is found in high amounts in olive oil. Polyunsaturated fatty acids are mostly derived from sea animals and vegetables - e.g. linoleic acid from fish oil or sunflower oil.
Triglycerides, also known as triacylglycerols, are more complex molecules. They are made up of three fatty acids attached to a backbone of glycerol. The molecule of triglyceride is hydrophobic and does not have any hydrophilic components. Triglycerides are a major source of energy that can be either used right away for energy production or stored in the body for meager times.
When the body needs energy, triglycerides derived from the diet or stored in adipocytes (which are fat cells) are broken down into fatty acids and glycerol by enzymes called lipases - proteins that break down lipids. The fatty acids are quickly absorbed by the muscle cells and tissues, where they can be used to generate energy. This is done by producing adenosine triphosphate (ATP), a biological molecule which can be used to power many chemical reactions. The body's process for producing energy from fatty acids is known as beta-oxidation.
Adenosine triphosphate (ATP) is a molecule which gives energy to cells in order to perform different functions such as muscle movements, nerve signals, and the production of other biomolecules, like proteins, DNA and RNA. It can be found in all living things and is known as the "molecular currency" that moves energy within cells. When it is used up, it turns into adenosine diphosphate (ADP) or adenosine monophosphate (AMP).
Nicotinamide adenine dinucleotide phosphate (NADP) is a reduced form of a coenzyme which plays a major role in the production of ATP by all living cells. Coenzyme is a molecule that helps enzymes to catalyze biochemical reaction.
The body stores triglycerides as an energy...
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