Cholesterol

7 Key excerpts on "Cholesterol"

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  eBook - ePub

  Medical Biochemistry

  Human Metabolism in Health and Disease

  • Miriam D. Rosenthal, Robert H. Glew(Authors)
  • 2011(Publication Date)
  • Wiley

    (Publisher)

  CHAPTER 17

  Cholesterol SYNTHESIS AND TRANSPORT

  17.1 FUNCTIONS OF Cholesterol

  Cholesterol is the major sterol in humans. The sterol structure of Cholesterol (Fig. 17-1) consists of four fused rings, three six-carbon and one five-carbon, designated A to D. Cholesterol has a hydroxyl group at C3, a C5–C6 carbon–carbon double bond, and two methyl groups, attached at positions C10 and C13 of the sterol ring. In addition, Cholesterol has a branched eight-carbon hydrocarbon chain attached to the D ring at C17.

  FIGURE 17-1

  Structure of Cholesterol.

  17.1.1 Cholesterol Is a Structural Component of Cellular Membranes

  Cholesterol is a ubiquitous and essential component of mammalian cell membranes. It is also present in small amounts in the outer membrane of mitochondria. Cholesterol is especially abundant in myelinated structures of the central nervous system, with 25% of the body’s Cholesterol located in the brain. In contrast to plasma, where most of the circulating Cholesterol exists esterified to a fatty acid, most Cholesterol in cellular membranes is present in the free (unesterified) form. The fluidity of membranes is regulated in part by changing their Cholesterol content.

  17.1.2 Cholesterol Is a Major Component of Bile

  Cholesterol is abundant in bile (normal concentration is about 15 mg per 100 mL, only 4% of which is esterified). The solubilization of free Cholesterol in bile is achieved in part by the detergent property of phosphatidylcholine, which is produced in liver and secreted into bile. Bile acids, which are metabolites of Cholesterol, also aid in solubilizing Cholesterol in bile. Increased biliary secretion of Cholesterol or decreased secretion of phospholipids or bile acids into bile may lead to deposition of Cholesterolrich gallstones. Indeed, the name Cholesterol was derived some 200 years ago from the Greek words chole (bile) + stereos

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  eBook - ePub

  Sweet Biochemistry

  Remembering Structures, Cycles, and Pathways by Mnemonics

  • Asha Kumari(Author)
  • 2017(Publication Date)
  • Academic Press

    (Publisher)

  Due to its unique bulky nucleus, Cholesterol is abundantly present in plasma membrane. The hydroxyl group at carbon 3 forms a hydrogen bond with the carbonyl oxygen atom of the phospholipid head group, whereas the hydrophobic tail adjusts to the lipophilic core of the membrane. Cholesterol inserts itself perpendicularly to the membrane plane of the phospholipid bilayer, where it interferes in reactions between fatty acids. The formation of lipid rafts is another important biological property of Cholesterol. Lipid rafts are stiff complexes of Cholesterol with phospholipids and proteins, they make membrane around them less fluid but some proteins present on lipid rafts act as receptors and channels.

  Cholesterol is the parent molecule of steroids like glucocorticoids, mineralocorticoids, reproductive hormones, and vitamin D. Bile acids are catabolic products of Cholesterol, which play a vital role in fat emulsification, which is required for fat and fat-soluble vitamin absorption.

  Honeycomb House-Cholesterol

  Figure 6.2 Cholesterol structure mnemonic with a rhyme sung by the Queen Bee.

  What Relates to Cholesterol in the Honeycomb House?

  3 bedrooms→3 cyclohexane rings 1 kitchen→one cyclopentane ring Double bed→double bond between C5 and C6 OH group at entrance→OH group at C3 On the roof, 2 methyl vents→methyl groups at C10 and C13 Antena→8-carbon side chain on C17

  Fig. 6.2

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  eBook - ePub

  The New Harvard Guide to Women's Health

  • Karen J. Carlson M.D., Stephanie A. Eisenstat M.D., Terra Ziporyn Ph.D.(Authors)
  • 2004(Publication Date)
  • Belknap Press

    (Publisher)

  Cholesterol

  Cholesterol is an odorless, white, powdery chemical manufactured by the liver and used to make essential body substances such as cell walls and hormones. It is part of every animal cell and is found in all foods that come from animals. In the bloodstream (which transports Cholesterol throughout the body), it is wrapped in protein “packages” called lipoproteins, which come in several forms. The lipoprotein that has been of greatest concern to investigators is low-density lipoprotein (LDL; sometimes referred to as “bad” Cholesterol). This protein contains a high percentage of Cholesterol relative to protein, and when LDL levels in the blood are high, cells lining the inside of the arteries transport LDL and its Cholesterol load into the artery wall, setting the stage for atherosclerosis.

  In atherosclerosis, scar tissue and fatty deposits build up in the walls of arteries throughout the body (see illustration). Eventually a clot can form on the surface of these obstructions, abruptly blocking the flow of blood in the already narrowed artery. If the blocked artery supplies blood to the heart, the result is a heart attack. If the artery supplies blood to the brain, the result may be a stroke.

  Numerous studies in middle-aged men have linked high LDL levels in the blood to an increased risk of heart attacks, stroke, and other vascular diseases. They have also established that lowering LDL Cholesterol in the blood reduces the risk of developing (and dying from) coronary artery disease (CAD). For years researchers have wondered whether these conclusions were equally valid for premenopausal women, who, because of the hormone estrogen, seem to metabolize Cholesterol differently. It now appears that there are some important distinctions between men and women when it comes to Cholesterol. For example, in women high levels of LDL in the blood seem not to be the best predictor of the risk of dying from cardiovascular disease and stroke, as they are in men. Rather, it is the level of HDL (high-density lipoprotein); that is, women with higher levels of HDL seem to have less coronary artery disease. This “good” Cholesterol contains a high percentage of protein relative to Cholesterol and is believed to take Cholesterol away

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  eBook - ePub

  Principles of Animal Nutrition

  • Guoyao Wu(Author)
  • 2017(Publication Date)
  • CRC Press

    (Publisher)

  Table 3.10 ) and highly abundant in the nervous system. Plasma chylomicrons and HDLs have the highest content of TAGs and proteins, respectively. The proportions of Cholesterols in lipoproteins have important implications for cardiovascular health.

  Derived lipids include steroids, eicosanoids, and terpenes. Steroids include sterols (e.g., Cholesterol) and their derivatives, such as steroid hormones (e.g., male and female reproductive hormones), bile acids, and bile alcohols that are synthesized in animals, as well as steroidal saponins that are present in plants. Eicosanoids are composed of series 1, 2, and 3 PGs and TXs with 1, 2, or 3 double bonds, as well as series 4 and 5 LTs and lipoxins with 4 or 5 double bonds. Terpenes, which have one or more isoprene units, include carotenoids, coenzyme Q, vitamins A, E, and K, essential oils, and phytols.

  Lipids undergo many reactions, such as the hydrolysis of TAGs, the saponification of fatty acids, esterification with alcohols, substitution of the hydroxyl hydrogen, hydrogenation of unsaturated fatty acids, peroxidation of unsaturated fatty acids, particularly at high temperatures, and reaction with chlorine or bromine. Although the diverse structures of lipids present challenges in their laboratory analysis, recent advances in chemistry have laid down a solid foundation for nutritional research on precursor fatty acids and their metabolites. Knowledge about the chemistry of lipids provides a foundation for our understanding of their metabolism and nutrition in animals (chapter 6).

  References

  Adeola, O., D.C. Mahan, M.J. Azain, S.K. Baidoo, G.L. Cromwell, G.M. Hill, J.E. Pettigrew, C.V. Maxwell, and M.C. Shannon. 2013. Dietary lipid sources and levels for weanling pigs. J. Anim. Sci. 91:4216–4225.

  Agellon, J.B. 2008. Metabolism and function of bile acids. In: Biochemistry of Lipids, Lipoproteins and Membranes (Fifth Edition)

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  eBook - ePub

  Biochemistry of Lipids, Lipoproteins and Membranes

  • Neale Ridgway, Roger McLeod(Authors)
  • 2008(Publication Date)
  • Elsevier Science

    (Publisher)

  Fig. 1 Model for membrane structure. This model of the plasma membrane of a eukaryotic cell is an adaptation of the original model proposed by Singer and Nicholson (S.J. Singer, 1972). The phospholipid bilayer is shown with integral membrane proteins largely containing α-helical transmembrane domains. Peripheral membrane proteins associate either with the lipid surface or with other membrane proteins. Lipid rafts (dark gray head groups) are enriched in Cholesterol and contain a phosphatidylinositol glycan-linked (GPI) protein. The light gray head groups depict lipids in close association with protein. The irregular surface and wavy acyl chains denote the fluid nature of the bilayer.

  In this chapter, the diversity in structure, chemical properties, and physical properties of lipids will be outlined. The various genetic approaches available to study lipid function in vivo will be summarized. Finally, how the physical and chemical properties of lipids relate to their multiple functions in living systems will be reviewed to provide a molecular basis for the diversity of lipid structures in natural membranes [1 ].

  2 Diversity in lipid structure

  Lipids are defined as the biological molecules readily soluble in organic solvents such as chloroform, ether, or toluene. However, many peptides and some very hydrophobic proteins are soluble in chloroform, and lipids with large hydrophilic domains such as saccharolipids are not soluble in these solvents. Here we will consider only those lipids that contribute significantly to membrane structure or have a role in determining protein structure or function. The broad area of lipids as second messengers is covered in Chapters 12 –14 . The LIPID Metabolites and Pathways Strategy (LIPID MAPS) consortium is identifying, characterizing, and classifying the components of the lipidome and developing a web-based systematic nomenclature for lipids and repository for structural information on lipids. The website of this consortium [2 ] provides a comprehensive and evolving picture of the lipodome.

  2.1 Glycerolipids

  The diacylglycerol backbone in eubacteria and eukaryotes is sn -3-glycerol esterified at positions 1 and 2 with long-chain fatty acids (Fig. 2 ). In archaebacteria (Fig. 3 ), the opposite isomer sn -1-glycerol forms the lipid backbone and the hydrophobic domain is composed of phytanyl (saturated isoprenyl) groups in ether linkage at positions 2 and 3 (an archaeol) [3 ]. In addition, two sn -1-glycerol groups are connected in ether linkage by two biphytanyl groups (dibiphytanyldiglycerophosphatetetraether) to form a covalently linked bilayer. Some eubacteria (mainly hyperthermophiles) have dialkyl (long-chain alcohols in ether linkage) phospholipids and similar ether linkages are found in the plasmalogens of eukaryotes. The head groups of the phospholipids (boxed area of Fig. 2 ) extend the diversity of lipids defining phosphatidic acid (PA, with OH), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidylinositol (PI), and cardiolipin (CL). Archaebacteria analogs exist with head groups of glycerol and glyceromethylphosphate as well as all of the above except PC and CL. Archaebacteria, also have neutral glycan lipid derivatives in which mono- and disaccharides (glucose or galactose) are directly linked to sn -1-archaeol (Fig. 3 ). Plants (mainly in the thylakoid membrane) and many gram-positive bacteria also have high levels of neutral diacylglycerol glycans with mono- or disaccharides linked to the 3-carbon of sn -3-glycerol (Chapter 4

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  The Liver

  Biology and Pathobiology

  • Irwin M. Arias, Harvey J. Alter, James L. Boyer, David E. Cohen, David A. Shafritz, Snorri S. Thorgeirsson, Allan W. Wolkoff(Authors)
  • 2020(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  22 Lipoprotein Metabolism and Cholesterol Balance Mariana Acuña‐Aravena and David E. Cohen

  Division of Gastroenterology and Hepatology, Joan & Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA

  INTRODUCTION

  Lipids are insoluble or sparingly soluble molecules that are essential for membrane biogenesis and maintenance of membrane integrity. They also serve as energy sources, hormone precursors, and signaling molecules. In order to facilitate transport through the relatively aqueous blood, nonpolar lipids, such as cholesteryl esters or triglycerides, are packaged within lipoproteins.

  Increased concentrations of certain lipoproteins in the circulation are associated strongly with atherosclerosis. Much of the prevalence of cardiovascular disease, the leading cause of death in the United States and most Western countries, can be attributed to elevated plasma concentrations of Cholesterol‐rich low‐density lipoprotein (LDL) particles, as well as lipoproteins that are rich in triglycerides. Epidemiologically, decreased concentrations of high‐density lipoprotein (HDL) Cholesterol also predispose to atherosclerotic disease. This chapter highlights the biochemistry and physiology of Cholesterol and lipoproteins. Because abundant clinical outcomes data have proven that morbidity and mortality from cardiovascular disease can be reduced by the use of lipid‐lowering drugs, mechanisms of pharmacologic interventions that can ameliorate hyperlipidemia will be discussed.

  BIOCHEMISTRY AND PHYSIOLOGY OF Cholesterol AND LIPOPROTEIN METABOLISM

  Lipoproteins are macromolecular aggregates that transport triglycerides and Cholesterol through the blood. Circulating lipoproteins can be differentiated on the basis of density, size, and protein content (Table 22.1

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  Yen & Jaffe's Reproductive Endocrinology E-Book

  Physiology, Pathophysiology, and Clinical Management

  • Antonio R. Gargiulo, Jerome F. Strauss, Robert L. Barbieri(Authors)
  • 2017(Publication Date)
  • Elsevier

    (Publisher)

  Chapter 4 Steroid Hormones and Other Lipid Molecules Involved in Human Reproduction Jerome F. Strauss III Garret A. FitzGerald Lipids serve as metabolic substrates, structural components of cellular membranes, and signaling molecules. This chapter reviews the diversity of lipid molecules that participate in signal transduction related to human reproduction, including the nomenclature, the general features of their synthesis and metabolism, the ways in which these processes are controlled physiologically, the ways in which they can be modified by pharmacologic intervention, and some disorders that interfere with normal synthesis and metabolism. The chapter emphasizes steroid hormones and eicosanoids because of their prominent roles in regulating sexual differentiation, the normal function of tissues involved in reproduction, and the pathophysiology of disorders affecting those tissues. Steroid Hormones: Structure and Nomenclature ◆ The steroid hormone backbone name is not synonymous with biological activity. ◆ The location of hydroxyl groups and whether they reside in the α (below the plane of the steroid nucleus) or β (above) configuration have major impact on the biological activity of steroid hormones. ◆ Synthetic “bioidentical” steroid hormones may contain a mixture of stereoisomers that affect potency. Steroid hormones and the secosteroid prohormone, vitamin D, belong to an ancient family of signaling molecules with diverse functions, including central roles in the regulation of female and male reproductive processes. The human steroid hormones are derived from Cholesterol, an abundant plasma lipid and a structural component of plasma membranes, and other organelles. Seemingly subtle modifications of the four fused rings of the sterol skeleton and side chain result in molecules with different activities. Steroid hormones share a cyclopentanoperhydrophenanthrene backbone

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