Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+. The free energy released in this process is used to form the high-energy molecules ATP and NADH. Glycolysis is a sequence of ten enzyme-catalyzed reactions. Most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates; the intermediates may be directly useful. For example, the intermediate dihydroxyacetone phosphate is a source of the glycerol that combines with fatty acids to form fat. Glycolysis is an oxygen-independent metabolic pathway; the wide occurrence of glycolysis indicates. Indeed, the reactions that constitute glycolysis and its parallel pathway, the pentose phosphate pathway, occur metal-catalyzed under the oxygen-free conditions of the Archean oceans in the absence of enzymes. In most organisms, glycolysis occurs in the cytosol; the most common type of glycolysis is the Embden–Meyerhof–Parnas, discovered by Gustav Embden, Otto Meyerhof, Jakub Karol Parnas.
Glycolysis refers to other pathways, such as the Entner–Doudoroff pathway and various heterofermentative and homofermentative pathways. However, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway; the glycolysis pathway can be separated into two phases: The Preparatory/Investment Phase – wherein ATP is consumed. The Pay Off Phase – wherein ATP is produced; the overall reaction of glycolysis is: The use of symbols in this equation makes it appear unbalanced with respect to oxygen atoms, hydrogen atoms, charges. Atom balance is maintained by the two phosphate groups: Each exists in the form of a hydrogen phosphate anion, dissociating to contribute 2 H+ overall Each liberates an oxygen atom when it binds to an ADP molecule, contributing 2 O overallCharges are balanced by the difference between ADP and ATP. In the cellular environment, all three hydroxyl groups of ADP dissociate into −O− and H+, giving ADP3−, this ion tends to exist in an ionic bond with Mg2+, giving ADPMg−.
ATP behaves identically except that it has four hydroxyl groups, giving ATPMg2−. When these differences along with the true charges on the two phosphate groups are considered together, the net charges of −4 on each side are balanced. For simple fermentations, the metabolism of one molecule of glucose to two molecules of pyruvate has a net yield of two molecules of ATP. Most cells will carry out further reactions to'repay' the used NAD+ and produce a final product of ethanol or lactic acid. Many bacteria use inorganic compounds as hydrogen acceptors to regenerate the NAD+. Cells performing aerobic respiration synthesize much more ATP, but not as part of glycolysis; these further aerobic reactions use pyruvate and NADH + H+ from glycolysis. Eukaryotic aerobic respiration produces 34 additional molecules of ATP for each glucose molecule, however most of these are produced by a vastly different mechanism to the substrate-level phosphorylation in glycolysis; the lower-energy production, per glucose, of anaerobic respiration relative to aerobic respiration, results in greater flux through the pathway under hypoxic conditions, unless alternative sources of anaerobically oxidizable substrates, such as fatty acids, are found.
The pathway of glycolysis as it is known today took 100 years to discover. The combined results of many smaller experiments were required in order to understand the pathway as a whole; the first steps in understanding glycolysis began in the nineteenth century with the wine industry. For economic reasons, the French wine industry sought to investigate why wine sometime turned distasteful, instead of fermenting into alcohol. French scientist Louis Pasteur researched this issue during the 1850s, the results of his experiments began the long road to elucidating the pathway of glycolysis, his experiments showed. While Pasteur's experiments were groundbreaking, insight into the component steps of glycolysis were provided by the non-cellular fermentation experiments of Eduard Buchner during the 1890s. Buchner demonstrated that the conversion of glucose to ethanol was possible using a non-living extract of yeast; this experiment not only revolutionized biochemistry, but allowed scientists to analyze this pathway in a more controlled lab setting.
In a series of experiments, scientists Arthur Harden and William Young discovered more pieces of glycolysis. They discovered the regulatory effects of ATP on glucose consumption during alcohol fermentation, they shed light on the role of one compound as a glycolysis intermediate: fructose 1,6-bisphosphate. The elucidation of fructose 1,6-bisphosphate was accomplished by measuring CO2 levels when yeast juice was incubated with glucose. CO2 production increased then slowed down. Harden and Young noted that this process would restart if an inorganic phosphate was added to the mixture. Harden and Young deduced that this process produced organic phosphate esters, further experiments allowed them to extract fructose diphosphate. Arthur Harden and William Young along with Nick Sheppard determined, in a second experiment, that a heat-sensitive high-molecular-weight subcellular fraction and a heat-insensitive low-molecular-weight cytoplasm fraction are required together for fermenta
Bile
Bile or gall is a dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver, stored and concentrated in the gallbladder. After eating, this stored bile is discharged into the duodenum; the composition of hepatic bile is 97% water, 0.7% bile salts, 0.2% bilirubin, 0.51% fats, 200 meq/l inorganic salts. About 400 to 800 ml of bile is produced per day in adult human beings. Bile or gall acts to some extent as a surfactant, helping to emulsify the lipids in food. Bile salt anions are hydrophobic on the other side; the hydrophilic sides are negatively charged, this charge prevents fat droplets coated with bile from re-aggregating into larger fat particles. Ordinarily, the micelles in the duodenum have a diameter around 14–33 μm; the dispersion of food fat into micelles provides a increased surface area for the action of the enzyme pancreatic lipase, which digests the triglycerides, is able to reach the fatty core through gaps between the bile salts.
A triglyceride is broken down into two fatty acids and a monoglyceride, which are absorbed by the villi on the intestine walls. After being transferred across the intestinal membrane, the fatty acids reform into triglycerides, before being absorbed into the lymphatic system through lacteals. Without bile salts, most of the lipids in food would be excreted in faeces, undigested. Since bile increases the absorption of fats, it is an important part of the absorption of the fat-soluble substances, such as the vitamins A, D, E, K. Besides its digestive function, bile serves as the route of excretion for bilirubin, a byproduct of red blood cells recycled by the liver. Bilirubin derives from hemoglobin by glucuronidation. Bile tends to be alkali on average; the pH of common duct bile is higher than that of the corresponding gallbladder bile. Bile in the gallbladder becomes more acidic the longer a person goes without eating, though resting slows this fall in pH; as an alkali, it has the function of neutralizing excess stomach acid before it enters the duodenum, the first section of the small intestine.
Bile salts act as bactericides, destroying many of the microbes that may be present in the food. In the absence of bile, fats become indigestible and are instead excreted in feces, a condition called steatorrhea. Feces lack their characteristic brown color and instead are white or gray, greasy. Steatorrhea can lead to deficiencies in fat-soluble vitamins. In addition, past the small intestine the gastrointestinal tract and gut flora are not adapted to processing fats, leading to problems in the large intestine; the cholesterol contained in bile will accrete into lumps in the gallbladder, forming gallstones. Cholesterol gallstones are treated through surgical removal of the gallbladder. However, they can sometimes be dissolved by increasing the concentration of certain occurring bile acids, such as chenodeoxycholic acid and ursodeoxycholic acid. On an empty stomach – after repeated vomiting, for example – a person's vomit may be green or dark yellow, bitter; the bitter and greenish component may be bile or normal digestive juices originating in the stomach.
The color of bile is likened to "fresh-cut grass", unlike components in the stomach that look greenish yellow or dark yellow. Bile may be forced into the stomach secondary to a weakened valve, the presence of certain drugs including alcohol, or powerful muscular contractions and duodenal spasms. Biliary obstruction refers to a condition when bile ducts which deliver bile from the gallbladder or liver to the duodenum become obstructed; the blockage of bile might cause a build up of bilirubin in the bloodstream which can result in jaundice. There are several potential causes for biliary obstruction including gallstones, trauma, choledocal cysts, or other benign causes of bile duct narrowing; the most common cause of bile duct obstruction is when gallstone are dislodged from the gallbladder into the cystic duct or common bile duct resulting in a blockage. A blockage of the gallbladder or cystic duct may cause cholecystitis. If the blockage is beyond the confluence of the pancreatic duct, this may cause gallstone pancreatitis.
In some instances of biliary obstruction, the bile may become infected by bacteria resulting in ascending cholangitis. In medical theories prevalent in the West from Classical Antiquity to the Middle Ages, the body's health depended on the equilibrium of four "humors", or vital fluids, two of which related to bile: blood, phlegm, "yellow bile", "black bile"; these "humors" are believed to have its roots in the appearance of a blood sedimentation test made in open air, which exhibits a dark clot at the bottom, a layer of unclotted erythrocytes, a layer of white blood cells and a layer of clear yellow serum. Excesses of black bile and yellow bile were thought to produce depression and aggression and the Greek names for them gave rise to the English words cholera and melancholia. In the former of those senses, the same theories explain the derivation of the English word bilious from bile, the meaning of gall in English as "exasperation" or "impudence", the Latin word cholera, derived from the Greek kholé, passed along in
Glycosome
The glycosome is a membrane-enclosed organelle that contains the glycolytic enzymes. The term was first used by Scott and Still in 1968 after they realized that the glycogen in the cell was not static but rather a dynamic molecule, it is found in a few species of protozoa including the Kinetoplastida which include the suborders Trypanosomatida and Bodonina, most notably in the human pathogenic trypanosomes, which can cause sleeping sickness, Chagas's disease, leishmaniasis. The organelle contains a dense proteinaceous matrix, it is believed to have evolved from the peroxisome. This has been verified by work done on Leishmania genetics; the glycosome is being researched as a possible target for drug therapies. Glycosomes are unique to kinetoplastids; the term glycosome is used for glycogen-containing structures found in hepatocytes responsible for storing sugar, but these are not membrane bound organelles. Glycosomes are composed of glycogen and proteins; the proteins are the enzymes. These proteins and glycogen form a complex to make a separate organelle.
The proteins for glycosomes are imported from free cytosolic ribosomes. The proteins imported into the organelle have a specific sequence, a PTS1 ending sequence to make sure they go to the right place, they are similar to alpha-granules in the cytosol of a cell. Glycosomes are round-to-oval shape with size varying in each cell. Although glycogen is found in the cytoplasm, that in the glycosome is separate, surrounded by membrane; the membrane is a lipid bilayer. The glycogen, found within the glycosome is identical to glycogen found in the cytosol. Glycosomes can be attached to many different types of organelles, they have been found to be attached to its intermediate filaments. Other glycosomes have been found to be attached to myofibrils and mitochondria, rough endoplasmic reticulum, polyribosomes, or the Golgi apparatus. Glycosome attachment may bestow a functional distinction between them; the glycosomes in the rough and smooth endoplasmic reticulum make use of its glycogen synthase and phosphorylase phosphatases.
Glycosomes function in many processes in the cell. These processes include glycolysis, purine salvage, beta oxidation of fatty acids, ether lipid synthesis; the main function that the glycosome serves is of the glycolytic pathway, done inside its membrane. By compartmentalizing glycolysis inside of the glycosome, the cell can be more successful. In the cell, action in the cytosol, the mitochondria, the glycosome are all completing the function of energy metabolism; this energy metabolism generates ATP through the process of glycolysis. The glycosome is a host of the main glycolytic enzymes in the pathway for glycolysis; this pathway is used to break down fatty acids for their energy. The entire process of glycolysis does not take place in the glycosome however. Rather, only the Embden-Meyerhof segment; the process in the organelle has no net ATP synthesis. This ATP comes from processes outside of the glycosome. Inside of the glycosome does need NAD + for its regeneration. Fructose 1,6-biphosphate is used in the glycosome as a way to help obtain oxidizing agents to help start glycolysis.
The glycosome converts the sugar into 3-phosphoglycerate. Another function of glycosomes is purine salvage; the parasites which have glycosomes present in their cells cannot make purine de novo. This purine, made in the glycosome is exported out of the glycosome to be used in the cell in nucleic acid. In other cells the enzymes responsible for this are present in the cytosol; these enzymes found in the glycosome to help with synthesis are guanine and adenine phosphoribosyl transferase and xanthine pho tran. All of these enzymes contain a PTS1 sequence at their carboxyl sequence so that they are sent to the glycosome. Microscopic techniques have revealed a lot about the glycosome in the cell and have indeed proven that there is a membrane-bound organelle in the cell for glycogen and its processes. Paul Erlich's findings as early as 1883 noted that from the microscope he could tell that glycogen in the cell was always found with what he called a carrier known to be protein; the glycogen itself was always seen in the cell towards the lower pole in one group, fixed.
When scientists tried to stain what was assumed was simple glycogen molecules, the staining had different outcomes. This is due to the fact that they weren't free glycogen molecules but a glycosome; the glycosome was studied in the microscope by examining the glycosome, stained with uranyl acetate. The U/Pb, seen stained was the protein, part of the glycosome; the glycogen in the glycosome in the cells is associated with protein, two to four times the weight of the glycogen. The glycogen itself however, after purified, is found with little protein, less than three percent showing that the glycosome is responsible and functions by having the proteins and enzymes needed for the glycogen in the glycosome. With the uranyl staining, as an acid, it would cause dissociation of the protein from the glycogen; the glycogen without the protein would form large aggregates and the stain would be the protein. This gives the illusion of glycogen disappearing as it is not stained, but it dissociates from the protein that it is associated with in the glycosome.
There has been a variety of evidence found biochemically to give
Endoplasmic reticulum
The endoplasmic reticulum is a type of organelle found in eukaryotic cells that forms an interconnected network of flattened, membrane-enclosed sacs or tube-like structures known as cisternae. The membranes of the ER are continuous with the outer nuclear membrane; the endoplasmic reticulum occurs in most types of eukaryotic cells, but is absent from red blood cells and spermatozoa. There are two types of ER: smooth endoplasmic reticulum; the outer face of the rough endoplasmic reticulum is studded with ribosomes that are the sites of protein synthesis. The rough endoplasmic reticulum is prominent in cells such as hepatocytes; the smooth endoplasmic reticulum lacks ribosomes and functions in lipid synthesis but not metabolism, the production of steroid hormones, detoxification. The smooth ER is abundant in mammalian liver and gonad cells; the ER was observed with light microscope by Garnier in 1897, who coined the term "ergastoplasm". With electron microscopy, the lacy membranes of the endoplasmic reticulum were first seen in 1945 by Keith R. Porter, Albert Claude, Ernest F. Fullam.
The word "reticulum", which means "network", was applied by Porter in 1953 to describe this fabric of membranes. The general structure of the endoplasmic reticulum is a network of membranes called cisternae; these sac-like structures are held together by the cytoskeleton. The phospholipid membrane encloses the cisternal space, continuous with the perinuclear space but separate from the cytosol; the functions of the endoplasmic reticulum can be summarized as the synthesis and export of proteins and membrane lipids, but varies between ER and cell type and cell function. The quantity of both rough and smooth endoplasmic reticulum in a cell can interchange from one type to the other, depending on the changing metabolic activities of the cell. Transformation can include embedding of new proteins in membrane as well as structural changes. Changes in protein content may occur without noticeable structural changes; the surface of the rough endoplasmic reticulum is studded with protein-manufacturing ribosomes giving it a "rough" appearance.
The binding site of the ribosome on the rough endoplasmic reticulum is the translocon. However, the ribosomes are not a stable part of this organelle's structure as they are being bound and released from the membrane. A ribosome only binds to the RER; this special complex forms when a free ribosome begins translating the mRNA of a protein destined for the secretory pathway. The first 5–30 amino acids polymerized encode a signal peptide, a molecular message, recognized and bound by a signal recognition particle. Translation pauses and the ribosome complex binds to the RER translocon where translation continues with the nascent protein forming into the RER lumen and/or membrane; the protein is processed in the ER lumen by an enzyme. Ribosomes at this point may be released back into the cytosol; the membrane of the rough endoplasmic reticulum forms large double membrane sheets that are located near, continuous with, the outer layer of the nuclear envelope. The double membrane sheets are stacked and connected through several right or left-handed helical ramps, the so-called Terasaki ramps, giving rise to a structure resembling a multi-storey car park.
Although there is no continuous membrane between the endoplasmic reticulum and the Golgi apparatus, membrane-bound transport vesicles shuttle proteins between these two compartments. Vesicles are surrounded by coating proteins called COPI and COPII. COPII targets vesicles to the Golgi apparatus and COPI marks them to be brought back to the rough endoplasmic reticulum; the rough endoplasmic reticulum works in concert with the Golgi complex to target new proteins to their proper destinations. A second method of transport out of the endoplasmic reticulum involves areas called membrane contact sites, where the membranes of the endoplasmic reticulum and other organelles are held together, allowing the transfer of lipids and other small molecules; the rough endoplasmic reticulum is key in multiple functions: Manufacture of lysosomal enzymes with a mannose-6-phosphate marker added in the cis-Golgi network. Manufacture of secreted proteins, either secreted constitutively with no tag or secreted in a regulatory manner involving clathrin and paired basic amino acids in the signal peptide.
Integral membrane proteins that stay embedded in the membrane as vesicles exit and bind to new membranes. Rab proteins are key in targeting the membrane. Initial glycosylation as assembly continues; this is N-linked. N-linked glycosylation: If the protein is properly folded, Oligosaccharyltransferase recognizes the AA sequence NXS or NXT and adds a 14-sugar backbone to the side-chain nitrogen of Asn. In most cells the smooth endoplasmic reticulum is scarce. Instead there are areas where the ER is smooth and rough, this area is called the transitional ER; the transitional ER gets its name. These are areas where the transport vesicles that contain lipids and proteins made in the ER, detach from the ER and start moving to the Golgi apparatus. Specialized cells can have a lot of smooth endoplasmic reticulum and in these cells the smooth ER has many functions
Mitosis
In cell biology, mitosis is a part of the cell cycle when replicated chromosomes are separated into two new nuclei. Cell division gives rise to genetically identical cells in which the number of chromosomes is maintained. In general, mitosis is preceded by the S stage of interphase and is accompanied or followed by cytokinesis, which divides the cytoplasm and cell membrane into two new cells containing equal shares of these cellular components. Mitosis and cytokinesis together define the mitotic phase of an animal cell cycle—the division of the mother cell into two daughter cells genetically identical to each other; the process of mitosis is divided into stages corresponding to the completion of one set of activities and the start of the next. These stages are prophase, metaphase and telophase. During mitosis, the chromosomes, which have duplicated and attach to spindle fibers that pull one copy of each chromosome to opposite sides of the cell; the result is two genetically identical daughter nuclei.
The rest of the cell may continue to divide by cytokinesis to produce two daughter cells. Producing three or more daughter cells instead of the normal two is a mitotic error called tripolar mitosis or multipolar mitosis. Other errors during mitosis can induce apoptosis or cause mutations. Certain types of cancer can arise from such mutations. Mitosis occurs only in eukaryotic cells. Prokaryotic cells, which lack a nucleus, divide by a different process called binary fission. Mitosis varies between organisms. For example, animal cells undergo an "open" mitosis, where the nuclear envelope breaks down before the chromosomes separate, whereas fungi undergo a "closed" mitosis, where chromosomes divide within an intact cell nucleus. Most animal cells undergo a shape change, known as mitotic cell rounding, to adopt a near spherical morphology at the start of mitosis. Most human cells are produced by mitotic cell division. Important exceptions include the gametes -- egg cells -- which are produced by meiosis.
Numerous descriptions of cell division were made during 18th and 19th centuries, with various degrees of accuracy. In 1835, the German botanist Hugo von Mohl, described cell division in the green alga Cladophora glomerata, stating that multiplication of cells occurs through cell division. In 1838, Schleiden affirmed that the formation of new cells in their interior was a general law for cell multiplication in plants, a view rejected in favour of Mohl model, due to contributions of Robert Remak and others. In animal cells, cell division with mitosis was discovered in frog and cat cornea cells in 1873 and described for the first time by the Polish histologist Wacław Mayzel in 1875. Bütschli and Fol might have claimed the discovery of the process presently known as "mitosis". In 1873, the German zoologist Otto Bütschli published data from observations on nematodes. A few years he discovered and described mitosis based on those observations; the term "mitosis", coined by Walther Flemming in 1882, is derived from the Greek word μίτος.
There are some alternative names for the process, e.g. "karyokinesis", a term introduced by Schleicher in 1878, or "equational division", proposed by Weismann in 1887. However, the term "mitosis" is used in a broad sense by some authors to refer to karyokinesis and cytokinesis together. Presently, "equational division" is more used to refer to meiosis II, the part of meiosis most like mitosis; the primary result of mitosis and cytokinesis is the transfer of a parent cell's genome into two daughter cells. The genome is composed of a number of chromosomes—complexes of coiled DNA that contain genetic information vital for proper cell function; because each resultant daughter cell should be genetically identical to the parent cell, the parent cell must make a copy of each chromosome before mitosis. This occurs during the S phase of interphase. Chromosome duplication results in two identical sister chromatids bound together by cohesin proteins at the centromere; when mitosis begins, the chromosomes become visible.
In some eukaryotes, for example animals, the nuclear envelope, which segregates the DNA from the cytoplasm, disintegrates into small vesicles. The nucleolus, which makes ribosomes in the cell disappears. Microtubules project from opposite ends of the cell, attach to the centromeres, align the chromosomes centrally within the cell; the microtubules contract to pull the sister chromatids of each chromosome apart. Sister chromatids at this point are called daughter chromosomes; as the cell elongates, corresponding daughter chromosomes are pulled toward opposite ends of the cell and condense maximally in late anaphase. A new nuclear envelope forms around the separated daughter chromosomes, which decondense to form interphase nuclei. During mitotic progression after the anaphase onset, the cell may undergo cytokinesis. In animal cells, a cell membrane pinches inward between the two developing nuclei to produce two new cells. In plant cells, a cell plate forms between the two nuclei. Cytokinesis does not always occur.
The mitotic phase is a short period of the cell cycle. It alternates with the much longer interphase, where the cell prepares itself for the process of cell division. Interphase is divided into three phases: G1, S, G2. During all three parts of interphase, the cell grows by producing proteins and cytoplasmic organelles. However, chromosomes are replicated only durin
Myelin
Myelin is a lipid-rich substance formed in the central nervous system by glial cells called oligodendrocytes, in the peripheral nervous system by Schwann cells. Myelin insulates nerve cell axons to increase the speed at which information travels from one nerve cell body to another or, for example, from a nerve cell body to a muscle; the myelinated axon can be likened to an electrical wire with insulating material around it. However, unlike the plastic covering on an electrical wire, myelin does not form a single long sheath over the entire length of the axon. Rather, each myelin sheath insulates the axon over a single section and, in general, each axon comprises multiple long myelinated sections separated from each other by short gaps called Nodes of Ranvier; each myelin sheath is formed by the concentric wrapping of an oligodendrocyte or Schwann cell process around the axon. More myelin speeds the transmission of electrical impulses called action potentials along myelinated axons by insulating the axon and reducing axonal membrane capacitance.
This results in saltatory conduction whereby the action potential "jumps" from one node of Ranvier, over a long myelinated stretch of the axon called the internode, before "recharging" at the next node of Ranvier, so on, until it reaches the axon terminal. Nodes of Ranvier are the short unmyelinated regions of the axon between adjacent long myelinated internodes. Once it reaches the axon terminal, this electrical signal provokes the release of a chemical message or neurotransmitter that binds to receptors on the adjacent post-synaptic cell at specialised regions called synapses; this "insulating" role for myelin is essential for normal motor function, sensory function and cognition, as demonstrated by the consequences of disorders that affect it, such as the genetically determined leukodystrophies. Due to its high prevalence, multiple sclerosis, which affects the central nervous system, is the best known disorder of myelin; the process of generating myelin is called myelination or myelinogenesis.
In the CNS, cells called oligodendrocyte precursor cells differentiate into mature oligodendrocytes, which form myelin. In humans, myelination begins early in the 3rd trimester, although only little myelin is present in either the CNS or the PNS at the time of birth. During infancy, myelination progresses with increasing numbers of axons acquiring myelin sheaths; this corresponds with the development of cognitive and motor skills, including language comprehension, speech acquisition and walking. Myelination continues through adolescence and early adulthood and although complete at this time, myelin sheaths can be added in grey matter regions such as the cerebral cortex, throughout life. Myelin is considered a defining characteristic of the jawed vertebrates, but axons are ensheathed by glial cells in invertebrates, although these glial-wraps are quite different from vertebrate compact myelin, formed, as indicated above, by concentric wrapping of the myelinating cell process multiple times around the axon.
Myelin was first described in 1854 by Rudolf Virchow, although it was over a century following the development of electron microscopy, that its glial cell origin and its ultrastructure became apparent. In vertebrates, not all axons are myelinated. For example, in the PNS, a large proportion of axons are unmyelinated. Instead, they are ensheathed by non-myelinating Schwann cells known as Remak SCs and arranged in Remak bundles. In the CNS, non-myelinated, intermingle with myelinated ones and are entwined, at least by the processes of another type of glial cell called the astrocyte. CNS myelin differs in composition and configuration from PNS myelin, but both perform the same "insulating" function. Being rich in lipid, myelin appears white. Both CNS white matter tracts and PNS nerves each comprise thousands to millions of axons aligned in parallel. Blood vessels provide the route for oxygen and energy substrates such as glucose to reach these fibre tracts, which contain other cell types including astrocytes and microglia in the CNS and macrophages in the PNS.
In terms of total mass, myelin comprises 40% water. Protein content includes myelin basic protein, abundant in the CNS where it plays a critical, non-redundant role in formation of compact myelin. In the PNS, myelin protein zero has a similar role to that of PLP in the CNS in that it is involved in holding together the multiple concentric layers of glial cell membrane that constitute the myelin sheath; the primary lipid of myelin is a glycolipid called galactocerebroside. The intertwining hydrocarbon chains of sphingomyelin strengthen the
Cholesterol
Cholesterol is an organic molecule. It is a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell membranes. Cholesterol serves as a precursor for the biosynthesis of steroid hormones, bile acid and vitamin D. Cholesterol is the principal sterol synthesized by all animals. In vertebrates, hepatic cells produce the greatest amounts, it is absent among prokaryotes, although there are some exceptions, such as Mycoplasma, which require cholesterol for growth. François Poulletier de la Salle first identified cholesterol in solid form in gallstones in 1769. However, it was not until 1815 that chemist Michel Eugène Chevreul named the compound "cholesterine". There is only one kind of cholesterol. There is no "good cholesterol" or "bad cholesterol"; the system that transports cholesterol where it is needed in the human body uses LDL and HDL to do so. Those are proteins, not lipids like cholesterol, neither of them are "bad", both are necessary to human health.
Cholesterol is essential for all animal life, with each cell capable of synthesizing it by way of a complex 37-step process. This begins with the mevalonate or HMG-CoA reductase pathway, the target of statin drugs, which encompasses the first 18 steps; this is followed by 19 additional steps to convert the resulting lanosterol into cholesterol. A human male weighing 68 kg synthesizes about 1 gram of cholesterol per day, his body contains about 35 g contained within the cell membranes. Typical daily cholesterol dietary intake for a man in the United States is 307 mg. Most ingested cholesterol is esterified; the body compensates for absorption of ingested cholesterol by reducing its own cholesterol synthesis. For these reasons, cholesterol in food, seven to ten hours after ingestion, has little, if any effect on concentrations of cholesterol in the blood. However, during the first seven hours after ingestion of cholesterol, as absorbed fats are being distributed around the body within extracellular water by the various lipoproteins, the concentrations increase.
Cholesterol is recycled in the body. The liver excretes it in a non-esterified form into the digestive tract. About 50% of the excreted cholesterol is reabsorbed by the small intestine back into the bloodstream. Plants make cholesterol in small amounts. Plants manufacture phytosterols, which can compete with cholesterol for reabsorption in the intestinal tract, thus reducing cholesterol reabsorption; when intestinal lining cells absorb phytosterols, in place of cholesterol, they excrete the phytosterol molecules back into the GI tract, an important protective mechanism. The intake of occurring phytosterols, which encompass plant sterols and stanols, ranges between ~200–300 mg/day depending on eating habits. Specially designed vegetarian experimental diets have been produced yielding upwards of 700 mg/day. Cholesterol, given that it composes about 30% of all animal cell membranes, is required to build and maintain membranes and modulates membrane fluidity over the range of physiological temperatures.
The hydroxyl group of each cholesterol molecule interacts with the water molecules surrounding the membrane as do the polar heads of the membrane phospholipids and sphingolipids, while the bulky steroid and the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty-acid chain of the other lipids. Through the interaction with the phospholipid fatty-acid chains, cholesterol increases membrane packing, which both alters membrane fluidity and maintains membrane integrity so that animal cells do not need to build cell walls; the membrane remains stable and durable without being rigid, allowing animal cells to change shape and animals to move. The structure of the tetracyclic ring of cholesterol contributes to the fluidity of the cell membrane, as the molecule is in a trans conformation making all but the side chain of cholesterol rigid and planar. In this structural role, cholesterol reduces the permeability of the plasma membrane to neutral solutes, hydrogen ions, sodium ions.
Within the cell membrane, cholesterol functions in intracellular transport, cell signaling and nerve conduction. Cholesterol is essential for the structure and function of invaginated caveolae and clathrin-coated pits, including caveola-dependent and clathrin-dependent endocytosis; the role of cholesterol in endocytosis of these types can be investigated by using methyl beta cyclodextrin to remove cholesterol from the plasma membrane. Recent studies show that cholesterol is implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane, which brings receptor proteins in close proximity with high concentrations of second messenger molecules. In multiple layers and phospholipids, both electrical insulators, can facilitate speed of transmission of electrical impulses along nerve tissue. For many neuron fibers, a myelin sheath, rich in cholesterol since it is derived from compacted layers of Schwann cell membrane, provides insulation for more efficient conduction of impulses.
Demyelination is believed to be part of the basis for multiple sclerosis. Within cells, cholesterol is a precursor molecule for several biochemical pathways. For example, it is the precursor molecule for the synthesis of vitamin D and all steroid hormones, including the adrenal gland ho
This article incorporates public domain material from the NCBI document "Science Primer".
