Cyclical Ketogenic Diets Review

Keto Resource

Many people always desire to lose weight within a short period. Dieting is easy the first few days, but without a plan, one is subjected to peer pressure and can easily fall back on their program. Gaining weight is very easy for most people, but losing it is another task that needs patience as it does not happen overnight. The Keto 28 day challenge works towards helping individuals achieve their dreams by losing weight on shorter duration of time as compared to other diet plans. It focuses on making its users lose weight and become lighter. The reason why most people gain more weight even when they are on a new diet is the lack of a plan. Lacking a diet plan makes one to make bad choices when choosing the type of food to eat and the quantities that they take. It's time to take the 28 day Keto challenge to get back in shape and have that good and light body that you have always desired. The plan also makes an individual sleep better, wake up more rested, improve hair growth, and have more energy as compared to the earlier days without Keto. Continue reading...

Keto Resource Summary


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Carbohydrate Microarrays Fabricated by Using Derivatized Carbohydrates

Derivatized carbohydrates, termed glycoligands, are carbohydrate moieties with functional tags prepared by chemical modification. Glycoligands provide more flexibility in the selection of array substrates and chemical-linking techniques for carbohydrate microarrays. Most importantly, the use of glycoligands in combination with properly functionalized surfaces allows for the site-specific immobilization of carbohydrates onto the substrates. With these technical features, it is possible to construct carbohydrate microarrays with control over the ways of presentation of carbohydrate moieties for molecular recognition. These characteristics are important for achieving the specificity or selectivity of carbohydrate-protein interactions that play importance roles in cell-cell communication, signaling, and modulation of immune responses (12,39,65). Microarray presentation of the native configurations of glycoepitopes is likely a challenging issue that requires substantial and relatively...

Embryo Implantation and Cell Surface Carbohydrates

Many reports suggested a role of cell surface carbohydrates in embryo implantation in the mouse. For example, type 1H and Ley antigens, both containing Fuca1 2Gal terminal structure, were implicated in mouse blastocyst implantation (4,14-16). Two fucosyltransferase genes, Futl and Fut2, responsible for Fuca1 2Gal terminal structure of these antigens were cloned and evaluated for their contribution to embryo implantation (17,18). However, neither Futl nor Fut2 nulls showed reproductive failure (18). This study excluded an essential role of Fuca1 2Gal terminated glycans in fertility in the mouse. Recently, a carbohydrate-binding protein, L-selectin, has been proposed as an adhesion molecule for human embryo implantation (19). L-Selectin is expressed on the surface of lymphocytes and interacts with sulfated and fucosylated carbohydrates expressed on lymph node endothelial cells (20-26). Carbohydrate ligand for L-selectin in the lymph node is closely related to MECA-79 antigen (Fig. 1)....

The Role of Cell Surface Carbohydrates in Cancer

Effective treatment for adenocarcinoma, the most aggressive form of cancer including prostate, breast, lung, colon, stomach, and endometrial cancers (85). Normal cellular counterparts of adenocarcinomas are epithelial cells, whose apical surfaces are covered by a thick layer known as the glycocalyx. When epithelial cells are transformed, the structure of cell surface carbohydrates changes (86-88). Monoclonal antibodies raised against adenocarcinoma are often specific to the cell surface carbohydrates expressed by cancer (89).

Carbohydrate Microarrays Fabricated by Using Underivatized Carbohydrates

The use of underivatized saccharides for microarray construction has the unique advantage of preserving the native structures of the carbohydrate molecules. It requires, however, a ready-to-use microarray surface with appropriate surface chemistry that can be directly used to fabricate comprehensive carbohydrate microarrays with underivatized carbohydrates from a wide range of sources. Methods include noncovalent binding of underivatized carbohydrate probes on a chip by passive adsorption and methods for covalently immobilizing underivatized carbohydrates on a slide surface by appropriate chemical-linking techniques. 1. Nonsite-Specific and Noncovalent Immobilization of Underivatized Carbohydrates in Microarrays Noncovalent adsorption of native carbohydrate probes on a substrate surface is the simplest way to prepare carbohydrate microarrays. This method relies on the formation of a variety of noncovalent interactions between the surface and the arrayed carbohydrates. In addition to...

Receptors for Carbohydrates

Receptors that recognize carbohydrates on the surface of microbes facilitate the phagocytosis of the microbes and stimulate subsequent adaptive immune responses. These receptors belong to the C-type lectin family, so called because they bind carbohydrates (hence, lectins) in a Ca++-dependent manner (hence, C-type). Some of these are soluble proteins found in the blood and extracellular fluids (discussed later) others are integral membrane proteins found on the surfaces of macrophages, dendritic cells, and some tissue cells. All these molecules contain a conserved carbohydrate recognition domain. There are several types of plasma membrane C-type lectins with specificities for different carbohydrates, including mannose, glucose, N-acetylglucosamine, and P-glucans. In general, these cell surface lectins recognize carbohydrate structures found on the cell walls of microorganisms but not mammalian cells. Some of these C-type lectin receptors function in the phagocytosis of microbes, and...

Nomenclature of Carbohydrates

Up to the 1940s, nomenclature proposals were made by individuals in some cases, they were followed by the scientific community and in some cases not. Official bodies like the International Union of Chemistry, though developing and expanding the Geneva nomenclature for organic compounds, made little progress with carbohydrate nomenclature. The International Union of Pure and Applied Chemistry (IUPAC) Commission on Nomenclature of Biological Chemistry put forward a classification scheme for carbohydrates, but the new terms proposed have not survived. However, in 1939, the American Chemical Society (ACS) formed a committee to look into this matter, since rapid progress in the field had led to various misnomers arising from the lack of guidelines (28). Within this committee, the foundations of modern systematic nomenclature for carbohydrates and derivatives were laid the numbering of the sugar chain, the use of d and l and a and p, and the designation of stereochemistry by italicized...

Lipids carbohydrates

Lipids form membranes inside and around the cell. Carbohydrates form complex tree-like molecules that become attached to the surface of proteins and cellular membranes. In both cases, the three-dimensional molecular structure is not unique, but the molecular assemblies are highly flexible. Thus, analyzing the molecular structure involves the inspection of a process in time. Molecular dynamics is the only available computer-based method for doing so. Compared with protein structures there are relatively few results on lipids and carbohydrates. The book does not detail this topic.

The Ketogenic Diet

Despite the many new antiepileptic drugs (AEDs), approximately 20 to 30 of children and adults continue to have seizures that are difficult to control. Some are candidates for epilepsy surgery to remove a seizure focus. Many must continue trying different medications. The ketogenic diet represents a promising, alternative therapeutic approach to improved seizure control for some children, and it is a potential but untested therapy for adults. A schematic diagram of the course of seizures and epilepsy and the role of the ketogenic diet is shown in Table 21.1 (1). The classic ketogenic diet high in fat, adequate in protein, and low in carbohydrates, was developed in the 1920s. The diet was initially designed to mimic the effects of starvation, which had been shown to have dramatic and long-lasting effects on the control of seizures. After the discovery of phenytoin, the classic ketogenic diet was used less frequently. The results of the study listed in Table 21.1 document the continued...

Immunology of Experimental Synthetic Carbohydrate Protein Conjugate Vaccines against Streptococcus pneumoniae Serotypes

The design and development of synthetic routes for the preparation of oligosaccharide fragments of capsular polysaccharides of Streptococcus pneumoniae serotypes took 25 years of intensive research at the Bijvoet Center. During that time sets of oligosaccharides of type 3, 6A, 6B, 14, and 23F were synthesized. Meanwhile, the Eijkman-Winkler Institute performed immunological studies on the effects of these carbohydrates in mice and rabbits. Different carriers (including liposomes), dosages, and adjuvants were tested in order to obtain high antibody titers with opsonic activity. Opsonization promoted the uptake and killing of bacteria by phagocytes, resulting in protective immunity to a lethal challenge with the corresponding virulent S. pneumoniae strain. The immunogenicity of synthetic oligosaccharide-protein conjugates was compared with that of polysaccharide-protein conjugates for the same serotypes of S. pneumoniae. The goal of the research at the Eijkman-Winkler Institute was to...


The aliphatic chains of glycolipids usually interact with CD1 molecules exposing the carbohydrates. This has led to the suggestion that each hydrophobic tail fits into a pocket of the CD1 groove. Consistent with this, binding studies demonstrated that the lipid portion of antigens is required for CD1 binding. Nevertheless, several unanswered questions remain opened such as for example what happens to the lipid fragments that cannot fit inside the groove, the selectivity of different CD1 molecules in binding particular lipids, and the stability of CD 1-lipids interactions (39). CDl-glycolipid complexes are expressed mainly on dendritic cells and other APC and some subsets of CD1 cells that express only CDlc as a unique group. The TCR of CD 1-restricted T-cells is highly discriminating, so that even monosaccharides that differ in the orientation of a single hydroxyl group can be distinguished. TCR presumably recognizes molecular surfaces composed of oc-helical amino acids of the CD1...

Origin and Nutrient Determinants

There are two energetic aspects of the food intake effect the first, and major one, is the obligatory expenditure in order to digest, absorb, distribute, and store the nutrients ingested the second is the facultative expenditure inducing additional heat production by activation of brown adipose tissue (BAT) 5 . The amount of energy required for handling incoming food is related to the type and the quantity of carbohydrates, fats, and proteins ingested. Fat is the least 'expensive' in terms of DIT, since it requires relatively little hydrolysis and has a fairly direct pathway to storage tissue (3-4 of ingested calories). Protein is the most 'expensive' for DIT, requiring expenditures up to 30 of the inherent energy for processing, which includes removal of nitrogen, synthesis of urea, and gluconeogenesis (on average,

Enzymatic Oligosaccharide Synthesis Processes

In contrast to the template-driven biosynthesis of nucleic acids and proteins, the biosynthesis of carbohydrates is defined as the cooperation of glycosyltransfer-ase machinery and their cofactors, sugar nucleotides. Chemical methods often require multiple protection-deprotection steps and long synthetic routes. As could be anticipated, the chemical synthesis of oligosaccharides is not an attractive option to industrial and scientific communities (105). Biocatalytic approaches employing enzymes or genetically engineered whole cells are, however, powerful and complementary alternatives to chemical methods (25).

Malnutrition Related Pancreatic Diabetes Mellitus

In tropical countries, there is another type of diabetes with many atypical clinical features. Hugh-Jones, in Jamaica, described the features of this type of diabetes and named it type J diabetes 32 . The features of this type include early-age onset of diabetes, a lack of ketosis, a relatively large insulin requirement, and lean body. Although many variants have been reported, the common features of this type of diabetes are malnutrition and protein deficiency.

Scientific Foundations

Biomass contains energy that has been stored from the sun. Plants use energy from the sun to convert water and carbon dioxide into a form that the plant use as energy, called carbohydrates. This process is called photosynthesis. The chemical energy gets stored in the plant, and when the plant is burned, the energy is released. This is why, for example, firewood burned in a fireplace can be used to heat a house.

Need for postruminal drug delivery systems and rumenstable products

Because of ruminal fermentation, some major developments in nutrition and veterinary science for simple-stomached farm animals cannot be applied directly to ruminants. For example, diets for poultry and swine have been routinely supplemented with limiting amino acids to improve productivity and feed efficiency. Dietary lipids are provided for poultry and swine to increase the level of some fatty acids in the tissue. Although highly productive ruminants may benefit from amino acid supplementation, direct addition of amino acids to the diet is not practical because ruminal microbes will utilize these amino acids before they reach absorption sites in the small intestine.1 Ruminal fermentation may also destroy or modify nutrients and drugs administered to prevent or treat disease. For example, unprotected glucose or starch given orally to prevent or treat ketosis will be almost completely metabolized to short-chain fatty acids in the rumen. To be efficacious, potent growth promoters which...

AGlucosidase inhibitors

Hypoglycemia in acarbose- or miglitol-treated subjects must be treated with simple carbohydrates found in milk, juices, or glucose tablets. Disaccharides or polysaccharides (sucrose (table sugar), candy, and soft drinks) cannot be used because the a-glucosidase inhibitory effects delay their hydrolysis and absorption. When used as monotherapy, acarbose and miglitol are not associated with hypoglycemia or significant weight changes. Blocking the absorption of complex carbohydrates decreases the caloric uptake of the small intestine, but the large intestine compensates to assure that adequate caloric goals are met. a-Glucosidase inhibitors do not significantly affect LDL or HDL cholesterol concentrations, but triglyceride levels decline. These agents may prove to be useful in the management of severe hypertriglyceridemia in both the diabetic and non-diabetic population.

ABO Blood Group Antigens

The ABO antigens are carbohydrates linked to cell surface proteins and lipids that are synthesized by polymorphic glycosyltransferase enzymes, which vary in activity depending on the inherited allele (Fig. 16-13). The ABO antigens were the first alloantigen system to be defined in mammals. All normal individuals synthesize a common core glycan, called the O antigen, that is mainly attached to plasma membrane proteins. Most individuals possess a fucosyltransferase that adds a fucose moiety to a nonterminal sugar residue of the O antigen, and the fucosylated glycan is called the H antigen. A single gene on chromosome 9 encodes a glycosyltransferase enzyme, which further modifies the H antigen. There are three allelic variants of this gene. The O allele gene product is devoid of enzymatic activity. The A allele-encoded enzyme transfers a terminal -acetylgalactosamine moiety, and the B allele gene product transfers a terminal galactose moiety. Individuals who are homozygous for the O...

Glycomic Databases And Servers

The advances in genomic and proteomic research have enabled many oligosaccharides of glycoproteins to be analyzed for their sequences, structures and functions. Thus the need exists for interfaces to bioinformatics tools constructed specifically for gly comes. The IUBMB site (http iubmb) offers general biochemical information for carbohydrates. General information, specifically keywords related to glycosciences including glycogene, glycoprotein, glycolipid, saccharide, glycotechnology and glycopathology, are available at GlycoWord On-line glycan structure databases are listed in Table 17.3.

Ruobing Wang Shaoyi Liu Dhaval Shah and Denong Wang Summary

We have established a high-throughput biochip platform for constructing carbohydrate microarrays. Using this technology, carbohydrate-containing macromolecules of diverse structures, including polysaccharides, natural glycoconjugates, and mono- and oligosac-charides coupled to carrier molecules, can be stably immobilized on a glass chip without chemical modification. Here, we describe a practical protocol for this technology. We hope that anyone who has access to a standard cDNA microarray facility will be able to explore this technology for his or her own research interest. We also provide an example to illustrate that the carbohydrate microarray is also a discovery tool this is particularly useful for identifying immunologic sugar moieties, including complex carbohydrates of cancer cells and sugar signatures of previously unrecognized microbial pathogens. Key Words Antigens antibodies carbohydrates glycans glyconjugates microarrays microspotting nitrocellulose polysaccharides...

To Probe Immunologic Sugar Moieties of SARSCoV

Third, we applied this probe to examine whether SARS-CoV expresses antigenic structures that imitate the host glycan. We confirmed that only the SARS-CoV-infected cells express PHA-L reactive antigenic structure (data not shown). Therefore, we obtained immunologic evidence that a carbohydrate structure of SARS-CoV shares antigenic similarity with host glycan complex carbohydrates. The biological significance of this finding remains to be further explored. For example, what is the possible involvement of autoimmune responses in SARS pathogenesis ASOR is an abundant human serum glycoprotein, and the ASOR-type complex carbohydrates are also expressed by other host glycoproteins (19,20). Thus, the human immune system is generally nonresponsive to these self carbohydrate structures. However, when similar sugar moieties were expressed by a viral glycoprotein, their cluster configuration could differ significantly from those displayed by a cellular glycan, thereby...

Concluding Remarks

Exploring the repertoires of glycoepitopes and their receptors represents a long-term goal of carbohydrate research. How big is the repertoire of glycoepi-topes Addressing this question is one of the most important topics in the postge-nomics era. It was estimated that there are about 500 endogenous glycoepitopes in mammals (17). However, this estimation did not consider the repertoires of the hybrid structures that are generated by protein posttranslational modification, including both N- and O-glycosylation. Furthermore, the conformational diversity of carbohydrates and microheterogeneity of carbohydrate chains substantially increases the repertoire of carbohydrate-based antigenic determinants or glycoepi-topes (39,63,66). Considering carbohydrate structures of the microbial world, which are directly relevant to medicine, the sizes and diversity of the repertoires of glycoepitopes are unpredictable. Establishment of high-throughput platforms of carbohydrate microarrays provides...

Metabolic Complications

Hyperglycaemia, hypercapnia, electrolyte abnormalities, and re-feeding syndrome are metabolic complications that can occur with enteral feeding. Complications are seen more often in diabetics and in patients receiving formulas with high caloric density. In diabetics, the use of hyperosmolar formulas can lead to hyperosmolar nonketotic coma. High carbohydrate concentrations may increase respiratory quotients and increase carbon dioxide production. Re-feeding syndrome is characterised by dehydration, hypernatraemia, hyper-chloraemia, and azotaemia. Its most common cause is the use of high-protein formulas with low water intake. This syndrome is seen among severely malnourished patients, such as alcoholics, when potassium and phosphorus requirements are high because of the intracellular shift that occurs when nutrients are replenished.

Energy Sources Carbohydrate and

Along with proper training, dietary choices have a strong influence on the amount of glucose stored in muscle. Diets high in carbohydrate stimulate muscles to store more glucose and can increase endurance.2,3 Athletes consuming 60-70 of calories as carbohydrates are better able to build large reserves of muscle glycogen than those consuming 40 of calories as carbohydrate (the normal amount of carbohydrate in the typical diet is about 45 ).2 For endurance athletes, at least two-thirds of total calories should come from carbohydrate. This means eating 500-600 g of carbohydrate each day. Emphasis should be on eating complex carbohydrates because, compared with simple carbohydrates, they contain more of the nutrients needed by athletes (they are richer in B vitamins, minerals, and fiber). Fat intake should be only 20-30 of total calories. Body fat stores, even in very lean athletes, contain much more fat than is needed during training or competition. For example, because each half kilo of...

Carbohydrate Microarrays

The microarray format bears many advantages the carbohydrates are attached mimicking their natural presentation on the cell surface multivalent interactions of binding molecules with the sugars are enabled, often a prerequisite of sugar interactions and only small amounts of sugars are needed for the fabrication of the microarray slide, overcoming a major problem, as the production of sugar compounds is still one of the main limitations for glycomics research. to bacterial RNA and inhibit bacterial protein expression. Using the microarrays, a high-throughput platform was established to screen for and develop better aminoglycoside antibiotics. The action of enzymes modifying carbohydrates was also investigated with carbohydrate chips. Microarrays bearing N-acetyllactosamine were incubated with a fucosyltransferase followed by a fucose-binding lectin to monitor successful action (21). Highly effective inhibitors were detected by adding various compounds in the incubation steps. Binding...

Carbohydrate Microarrrays to Detect Pathogens and Viruses

Virtually all cells are surrounded by a layer of proteins and carbohydrates covering the plasma membrane to protect the cell from the surrounding and to regulate cell interactions with the environment (1). Many proteins interact with the sugars on the cell surface mediating cell signaling and cell adhesion. However, various viruses and bacteria also bear proteins that bind to the target host cell, often initializing entry into the cell (51,52). Binding of influenza viruses to the human cell surface is mediated by the hem-agglutinin (HA) proteins. The attachment initiates the uptake of the virus particle into the host cell. Influenza HAs bind to carbohydrates bearing sialic acids (N-acetylneuraminic acid). The human influenza virus HA proteins preferentially bind to a2-6-linked sialic acids (Fig. 8A) that are found in the upper respiratory tract of humans. In contrast, avian HA proteins preferentially bind to a2-3-linked sialic acid (Fig. 8B) (61-63). Glycans of this type occur in the...

Tracers for the study of triglyceriderich lipoprotein kinetics Chylomicrons

Chylomicrons are large lipoprotein particles that are formed by the small intestine during fat absorption. The amount of lipid fuel that traverses the circulation in the form of chylomicrons obviously varies with dietary fat consumption. In individuals on high-fat diets, however, it can equal or exceed FFA flux (Miles et al. 2004). The triglyceride transported in chylomicrons is metabolised by LPL, which is widely distributed in tissues but is most abundant in adipose tissue and skeletal muscle (Eckel 1989). Nascent chylomicrons have a short residence time in the circulation, with a half life of approximately five minutes (Park et al. 2001). Chylomicron half life is prolonged at higher chylomicron triglyceride concentrations (Park et al. 2001).

Selective Oxidation of the Primary Hydroxyl Group

Platinum (catalyst) and molecular oxygen (oxidant) have been used to selectively oxidize carbohydrates (Abbadi and van Bekkum, 1996 Gallezot and Besson, 1995) such as sucrose (Fritsche-Lang et al., 1985 Kunz and Recker, 1995). Inulin is readily oxidized using O2 and platinum in the presence of sodium hydroxide (Verraest et al., 1998). Oxidation occurs selectively at the C-6 position with a relatively high yield (79 ). Sucrose is also selectively oxidized at the C-6 and C-6' positions under similar conditions (Edye et al., 1991, 1994). The molecular weight of the inulin influences the reaction rate and degree of oxidation. Nystose (GF3) had a degree of oxidation of 40 . As the chain length increases, the degree of oxidation declines. Inulin with an average degree of polymerization of 10 had a degree of oxidation of 28 , while at an average degree of polymerization of 30, it decreased to only 20 . In addition, the amount of by-products increases with increasing chain length and degree...

Inulin and Diabetes Mellitus

Of sucrose or glucose prompts blood sugar and insulin changes, but no corresponding effects are noted when equivalent amounts of inulin or fructooligosaccharides are ingested (Roch-Norlund et al., 1972). Therefore, consuming inulin-rich foods helps to restore normal levels of blood sugar, whereas foods containing starch and sucrose further raise blood sugar levels. Experiments during the 1980s and 1990s confirmed the beneficial role of inulin-rich foods in diabetic diets. Daily intake of fructooligosaccharides has been shown to reduce blood sugar levels in both diabetic and healthy subjects (Luo et al., 1996 Yamashita et al., 1984), for instance, while inulin reduced insulin peaks compared to diets containing other carbohydrates (Rumessen et al., 1990). An intake of around 16 to 23 g of inulin per meal has been recommended in diabetic diets (Van Loo et al., 1995). There is a long history of inulin-containing plants being used to treat diabetes. The Greek physician Theophrastus used...

Summary and Conclusions

Matrix-assisted laser desorption ionization mass spectrometry of carbohydrates. Mass Spectrom Rev 1999 18 349-450. 48. Siegel MM, Tabei K, Kagan MZ, Vlahov IR, Hileman RE, Linhardt RJ. Polysulfated carbohydrates analyzed as ion-paired complexes with basic peptides and proteins using electrospray negative ionization mass spectrometry. J Mass Spectrom 1997 32 760-772.

Biochemical Mechanisms

Although the causes of DIT are not very clear, the mechanisms perhaps responsible for adaptive thermogenesis may be related to adenosine triphosphate (ATP) production and utilisation. In animal tissues, six different pathways for ATP production have been identified two through anaerobic glycolysis of carbohydrates, one involving oxidative decarboxylation of carboxylic chetoacids, and three associated with electron transport to molecular oxygen. The energy required for ATP synthesis varies with the substrate considered, according to their different caloric value per 100 g, and to the yield in ATP per 100 g. The energy needed to produce 1 mol of ATP is therefore less for carbohydrates than for fats and proteins (Table 1). Table 1. Factors related to the energy available from ingested fats, carbohydrates and proteins. (Adapted from 4 ) Table 1. Factors related to the energy available from ingested fats, carbohydrates and proteins. (Adapted from 4 ) Carbohydrates

Management of the Metabolic Syndrome

Healthy lifestyle promotion includes (1) dietary changes in terms of moderating calorie intake to achieve a 5-10 loss of body weight in the first year and changing dietary composition (2) increasing physical activity and (3) changes in dietary composition to lower intake of saturated fats, trans fats and cholesterol, and include carbohydrates with a low glycemic index and high content of soluble fiber.

Nutrition and Epilepsy

Nutrition plays a central role in health and disease processes. The body draws all of its resources except oxygen from the diet. What we consume and how much we consume determines these resources and can influence health and disease. The traditional balanced diet recommended by the American Dietetic Association (ADA) consists of a mixture high in carbohydrates, moderate in protein, and low in fats. Some researchers are criticizing this once accepted food pyramid model that was the framework for a healthy diet for nearly 30 years. Studies on the Atkins diet, a high protein, low carbohydrate diet, support its utility as an effective means for weight loss, but no evidence relates its effects on seizures or long-term safety (1). The ketogenic diet, which is high fat and extremely low in carbohydrates, can help control seizures in some patients (see Chapter 21). Fasting rarely provokes seizures, and actually may reduce seizure frequency by putting the body in a state of ketosis (2,3)....

Retinal Detachment Proliferative Vitreoretinopathy

The carbohydrates of the posterior vitreoretinal juncture were examined by electron microscopy (57). Globular material of intermediate electron density was found in the basement membrane of the retina and on collagen fibrils in the vitreous cortex after cetylpyridinium chloride fixation and disappeared after Streptomyces hyaluronidase digestion. These observations suggest that the globular material is hyaluronan that is more labile along the basement membrane than toward the inner vitreous cortex. A fine filamentous network may be formed by the oligosaccharide chains associated with vitreous proteins as part of the vitreoretinal juncture layer.

The Human Adipose Organ

The reduced lipolytic activity appears to stem from a relative preponderance of the antilipolytic activity of a2-ARs over that of lipolytic p-ARs 91 . In general, a2-ARs are more represented in human than murine adipose tissue. Transgenic mice with adipose tissue similar to human fat tissue have been obtained to mimic this situation in a murine model. These animals lack p3-ARs and express abundantly human a 2-AR (p 3-AR-deficient, human a2-expressing transgenic mice) 92 . In these animals obesity induced by a high-fat diet was exclusively of the hyperplastic type and the mice were not insulin-resistant. These data are in line with the important role of a2-AR in relation to the proliferative stimulus, and with the relationship between insulin sensitivity and adipocyte size.

Energy Values of Foods

Foods contain various amounts of organic oxi-disable substrates that can be utilised to yield energy. The best substrates are the same as those present in the cells of the human organism, i.e. protein, carbohydrates and fats, since the cellular apparatus is equipped with enzymes and other necessary components for the metabolism of these compounds. However, even compounds that are not naturally present in cells, such as alcohol, may be utilised for energy production since they can be metabolised by existing, or inducible enzymes.

Dimension of the Nutritional Problem in the World

A diet unbalanced in macronutrients, which are the energy-providing food components, is also a cause for concern, even when total energy intake is adequate. The healthy range of macronutrient intake, expressed as a percent of total energy, can be broad 55-75 from carbohydrates, 15-35 from fats, and 10-15 from proteins. A more modern balance of energy intake should be suggested, for example 40 from carbohydrates, 30 from proteins, and 30 from fats.

Nonnutrient Dietary Components

Non-nutrient substances, i.e. those other than carbohydrates, fats and proteins, are present as minor components of foods and may have an effect on DIT examples of non-nutrient substances include caffeine, spices, and nicotine. A thermogenic stimulating effect has been found in green tea, attributed to its caffeine and catechin polyphenols content. Since the latter is capable of inhibiting the enzyme that degrades noradrenaline (catechol-o-methyl transferase) and caffeine inhibits transcellular phos-phodiesterases (enzymes that break down nora-

Protein Requirement and Energy Intake

It has been proposed that protein requirement is, within a certain limit, inversely dependent on energy intake, i.e. the more energy is ingested, the less protein is needed (Table 4). This is because proteins can be used also as energy sources (beyond their structural, regulatory and functional role). Therefore, if their use to produce energy varies, their requirement also varies. Furthermore, alternative energy substrates, such as the carbohydrates, can stimulate insulin secretion, which in turn spares endogenous proteins 18 .

Cereals Bread Wheat Bran and Wheat Germ

Whole grains are the best natural sources of complex carbohydrates and fiber. Populations eating large amounts of whole-grain products (e.g., Africa and Asia) have far fewer intestinal and bowel problems-such as constipation, hemorrhoids, diverticulitis, and colon cancer-compared to Western populations consuming mainly refined carbohydrates.30

Synthesis Assembly And Expression Of Ig Molecules

Immunoglobulin heavy and light chains, like most secreted and membrane proteins, are synthesized on membrane-bound ribosomes in the rough endoplasmic reticulum. The protein is translocated into the endoplas-mic reticulum, and Ig heavy chains are N-glycosylated during the translocation process. The proper folding of Ig heavy chains and their assembly with light chains are regulated by proteins resident in the endoplasmic reticu-lum called chaperones. These proteins, which include calnexin and a molecule called BiP (binding protein), bind to newly synthesized Ig polypeptides and ensure that they are retained or targeted for degradation unless they fold properly and assemble into complete Ig molecules. The covalent association of heavy and light chains, stabilized by the formation of disulfide bonds, is part of the assembly process and also occurs in the endoplasmic reticulum. After assembly, the Ig molecules are released from chaperones, transported into the cisternae of the Golgi...

Intraluminal Nutrients

Intraluminal nutrients increase gut perception, and this effect depends on the concentration and the type of nutrient. At physiological loads, lipids have a marked effect, but the influence of carbohydrates is much weaker (28). Nutrients modify gut motor activity, but their effects on perception are independent. Indeed, the sensitization induced by lipids seems specifically related to mechano-receptors, because perception of transmucosal electrical stimulation of the gut, which activates gut afferents without relaying on any specific receptor, is not modified by intraluminal lipids (27). Cho-lecystokinin (CCK) has been shown to increase the mechanoreceptive response (29), and hence, it could be involved in these effects. Furthermore, in the presence of intestinal lipids, loxiglumide, a CCK-A receptor antagonist, reduces perception of gastric distension (30).

Cell Cell Interactions and Signalling

1 Extracellular matrix refers to the environment filling the spaces between cells. The extracellular matrix is a complex three dimensional network of proteins and carbohydrates secreted and remodelled by the cell. It helps bind the cells together in tissues and also provides a lattice through which cells can move.

Features of Biologic Antigens

An antigen is any substance that may be specifically bound by an antibody molecule or T cell receptor. Antibodies can recognize as antigens almost every kind of biologic molecule, including simple intermediary metabolites, sugars, lipids, autacoids, and hormones, as well as macromolecules such as complex carbohydrates, phos-pholipids, nucleic acids, and proteins. This is in contrast to T cells, which mainly recognize peptides (see Chapter 6). Any available shape or surface on a molecule that may be recognized by an antibody constitutes an antigenic determinant or epitope. Antigenic determinants may be delineated on any type of compound, including but not restricted to carbohydrates, proteins, lipids, and nucleic acids. In the case of proteins, the formation of some determinants depends only on the primary structure, and the formation of other determinants reflects tertiary structure, or conformation (shape) (Fig. 5-12). Epitopes formed by several adjacent amino acid residues are...

Vegetables and Fruits

Vegetables and fruits are the cornerstones of a healthy diet. They are rich sources of vitamins, minerals, complex carbohydrates, and fiber. Some, such as peas and corn, are also good sources of protein. Moreover, vegetables and fruits are generally inexpensive, contain no cholesterol, have little or no fat, and are low in calories. A high intake of vegetables, particularly of the Brassica family (broccoli, cabbage, cauliflower, and Brussels sprouts) can sharply reduce the risk of cancer.10 These vegetables contain compounds that can help the body detoxify and clear potential carcinogens. In addition, fruits and vegetables are rich sources of antioxidant nutrients, such as beta carotene and vitamin C, that may also protect against cancer and heart disease.21,22

Agriculture Seeks to Maximize Photosynthesis

Recall from Chapter 2 that plants, along with algae and some bacteria, transform light energy into chemical energy via the process of photosynthesis. Photosynthesis converts the energy from sunlight, carbon dioxide from the atmosphere, and water into energy-rich molecules called carbohydrates. Plants then use carbohydrates to run the activities of their cells. In other words, plants make their own food. In fact, plants are so effective at converting light energy into chemical energy that they produce enough energy to store and to grow larger. Other organisms, such as humans, harvest this excess energy. Our agricultural practices are intended to maximize the photosynthesis of crop plants so they will produce a surplus of carbohydrates we can harvest.

Heparin and Heparan Sulphate Sequencing

The ability to sequence heparin and more specifically heparan sulphate is of fundamental importance in the determination of structure-function relationships between the carbohydrate and its many interacting partners. Unlike protein and nucleic acid sequencing, the sequencing of carbohydrates and more specifically that of glycosaminoglycans has lagged behind with no one individual method allowing for facile, reproducible sequence determination of an oligosaccharide (and certainly not a polysaccharide) chain of any sizeable length.

Hyperlipidemia and atherosclerosis

Atherosclerotic plaques was controversial with much emphasis placed on the vascular smooth muscle cell. Although other authors had described monocytes in atherosclerotic lesions, this paper carefully studies the progression of atheroma at different time points and characterizes the lesion composition. Yorkshire pigs were fed a normal chow or high-fat chow and sacrificed at 6, 12, 15 and 30 weeks after the initiation of diet. At 15 weeks following high-fat chow, lesions were always of a foam cell nature, confined to the intima, with no evidence of medial cell involvement in the intima or engorgement of smooth muscle cells with lipid . Monocytes were identified using various histo-logical criteria. At 30 weeks following high-fat diet, fibrous lesions were described as fibrous caps overlying necrotic lipid cores. Gerrity hypothesized, based on this and earlier studies from his group, that blood-derived monocytes adhere to the endothelium, which is not necessarily associated with...

Medium Chain Triglycerides

In MAC-16 tumours, an anti-cachectic effect can be obtained, together with a reduction of tumour mass, by administration of amount of MCT 80 of the required energy 58, 60 . Cachexia and tumour growth rate 61 can be reduced by replacing a portion of dietary carbohydrates with lipid derivatives of fish oil at 50 of the total calories in the animal diet. Even those neoplastic patients with a weight loss 32 , can recover their weight with isocaloric diets in which energy is supplied by MCT at 70 62 .

Modeling of Phase 2 Metabolism Enzymes

Sulfate conjugation generally produces a highly water-soluble sulfuric acid ester. The reaction is catalyzed by SULTs, a large gene family of soluble (cytosolic) enzymes, and involves transfer of a sulfonate (SO ). The required cofactor for the reaction is 3'-phosphoadenosine 5'-phosphosulfate (PAPS).68'108 Although the most common substrates for this enzyme are phenols and aliphatic alcohols, metabolism is not limited to those classes.68 In mammals, sulfation is involved in the detoxification of therapeutic, dietary, and environmental xenobiotics, and contributes to the homeostasis and regulation of numerous biologically active endogenous chemicals such as steroids, iodothyronines, bile acids, and neurotransmitters.109,110 In addition, for a large number of procarcinogens sulfation is the terminal step in the bioactivation pathway, and is necessary to reveal their mutagenic carcinogenic activity. Multiple SULTs have been identified in all mammalian species, and are members of five...

Nutrients Deficiency and Diarrhoea

Under physiological conditions, each nutrient is absorbed at a specific site of the small intestine. The majority of carbohydrates, proteins, and fats are normally absorbed within the first 150 cm of small bowel. Folic acid, calcium, magnesium, iron, vitamin C, and fat-soluble vitamins (A, D, E, and K) are also absorbed in the proximal intestine. Thus, resection of the proximal intestine means a reduction in the absorption area for these nutrients. In addition, the loss of intestinal lactase, sucrase-isomaltase, and a-dextrinase, resulting from resection of the proximal bowel, induces carbohydrates malabsorption. Of the disaccharidases, lactase levels are the most prone to decrease, resulting in luminal hyperosmolarity. Bacterial fermentation of lactose leads to large amounts of lactic acid, which further induce osmotic diarrhoea 51 .

Energy Values from the Food Composition Tables

For carbohydrates, a value of 3.75 Kcal g, when expressed as monosaccharides (corresponding to the physical value), is used. In the case of disac-charides, because the molecular weight of a monosaccharide is higher than that of a disaccha-ride molecule, a factor of 1.05 is applied and the energy value is 3.75 x 1.05 3.94 Kcal g. In the case of starch, the factor is 1.10 and the energy value is 4.125 Kcal g 8 . Together, the monosaccharides + disaccharides + starch represent the available carbohydrates. Cellulose, hemicellulose, pectin, gums, and resistant starch* (collectively referred to as dietary fibre or unavailable carbohydrates) are not considered to have energetic value. However, unavailable, unaltered carbohydrates reach the colon, where they can be fermented by the local microflora, which consist of several genera of anaerobic microorganisms. These utilise dietary fibre to produce pyruvic acid, an important metabolic intermediate from which short-chain fatty acids (SCFA),...

Body fat distribution and insulin resistance Skeletal muscle intramyocellular lipids

The first part was shown to be true in the case of a three days (Bachmann et al. 2001) high fat diet and intravenous intralipid heparin infusion induced peripheral insulin resistance (Bachmann et al. 2001 Boden et al. 2001). Researchers could observe a parallel increase of IMCL content, relatively more pronounced in the tibialis anterior muscle of young healthy humans (Bachmann et al. 2001 Boden et al. 2001). Similar results, accompanied by molecular adaptations favouring fat storage in muscle, were found in another study after one week of high fat diet (Schrauwen-Hinderling et al. 2005). Inducing insulin resistance by i.v. amino acid infusion during euglycaemic-hyperinsulinaemia (Krebs et al. 2001) was met by a subtle increase of IMCL content in soleus muscle. IMCL content decreased with increasing insulin sensitivity due to 8-10 months of leptin replacement in patients generalised lipodystrophy (Simha et al. 2003) and 6 months of caloric restriction with or without exercise in an...

Inhibition of Glycosidases and Glycosyltransferases

Glycosidases are responsible for the cleavage of the glycosidic bond in carbohydrates. These enzymes are involved in numerous biological processes. The transition state of the reactions catalyzed by glycosidases and by glycosyltransferases involves an intermediate in which the anomeric carbon has a very pronounced alkoxycarbenium character. Such a cationic transition state is destabilized by the presence of an electron-withdrawing substituent a fluorine atom in b or a CF3 group in a, for example. Thus, the formation of this intermediate requires a high activation energy. However, if the substrate bears an excellent leaving group, the formation of an intermediate bonded to the enzyme is possible. In this case, the formed bond is strong enough not to be further cleaved. Indeed, the presence of a fluorinated substituent renders the carboxylate of an aspartic acid of the enzyme less effective as a leaving group (Figure 7.28).8g This leads to accumulation of the intermediate, and thus...

Nutritional Support

The objective of nutritional support in patients with liver cirrhosis is to provide adequate calories, protein, and other nutrients to ensure the availability of synthetic and energy substrates to hepatocytes without inducing hepatic encephalopathy (Table 6) 76, 77 . In general, cirrhotic patients without encephalopathy require no restriction of protein, but a diet high in complex carbohydrates and calories and supplemented with multivitamins, calcium,


Grossly, the brain is large and shows leptomeninges thickened from deposits of mucopolysaccharides in vascular endothelium and fibrous tissue. The ventricles are enlarged due to communicating obstructive hydroceph-alus. The histology is characterized by the neuronal storage of a mixture of gangliosides that stain positively for lipids and carbohydrates. Dilated perivascular spaces are filled with foamy macrophages (see Fig. 9.8).

Treatment by CAM Providers

In additional to a plethora of antiepileptic drugs (AEDs) commonly used today, a number of nonpharmacological options are available. Two of these approaches, the ketogenic diet (high-fat, low-protein, and low-carbohydrate) and vagal nerve stimulation (implantation of a stimulating device in the chest wall), are well supported by the literature. In addition, after chiropractic adjustments (often directed to the upper cervical region), several case studies (2,34-38) have documented improvements in patients with epileptic seizures. The use of acupuncture, yoga, and a host of supplements has been met with much more limited success.

Carbohydrate Polymers as Wound Dressings A Wound Dressing

Role(s) of Carbohydrates Figure 1 An injury can be defined as a discontinuity in tissue integrity and healing as a process of restoring that integrity. Skin has two main forms of healing with very different outcomes in terms of appearance and function. Carbohydrates are used in a number of roles to enhance healing.

Strategies of Skin Tissue Engineering

There are two basic roles for carbohydrates in the field of skin replacement. These relate to the bilaminar nature of the skin with the dermal matrix and the cellular epidermis. The matrix is a biomechanical construct and can be made. As already described, there are collagenous and noncollagenous components in the human dermis. There is and has been a considerable amount of research to explore the roles of collagen and GAG polymers in matrix production. Indeed, this is a feature of research and reviews spanning the last two decades. The most successful commercial product is Integra, which was approved for clinical use in 1996 both in the United States and Europe.

Embryonic Development

Embryonic and Postnatal-Lethality in MX MII Double Deficient Mutant Although it is widely assumed that cell surface carbohydrates play a significant role in mammalian embryonic development, the first evidence for this hypothesis came from the GnT-I gene knockout mouse, which dies at early embryonic stages (65,66). We generated MII MX double-null mutant mice by crossing MII- and MX-null mice. All double-null embryos survived until E15, but some double nulls died between E15 and the day of birth (E18). The majority of double nulls died soon after birth, with many double-null neonates dying after gasping for air at birth, suggesting that neonatal lethality is due to respiratory failure (69). In summary, gene knockout mouse technology has allowed us to determine the function of cell surface carbohydrates in mouse embryos in recent years. Some glycosyltransferases-deficient mutant mouse showed severe phenotypes, including embryonic lethality. However, we have not yet identified the...

Effect of Intestinal Microbiota on the Immune System Preclinical Studies

In the same experiments, different classical fiber mixtures in a similar dose to the GOS lcFOS mixture were tested. There was no effect of these fibers on the measured parameter of the immune system, indicating that different nondigestible carbohydrates react differently with respect to intestinal microbiota and immune function (71).

The Contribution of Emil Fischer

During the last two decades of the nineteenth century, Emil Fischer (8) began his fundamental studies on carbohydrates, showing that phenylhydrazine reacts with glucose, mannose, and fructose to give the same crystalline phenylosazone, and he utilized the reaction introduced by Kiliani, the addition of hydrogen cyanide to a sugar, to give two isomeric acids. In his 1890 address to the German Chemical Society (9), he showed that Traubenzucker is a 2,3,4,5,6-pentahydroxyhexanal and that Fruchtzucker is a 1,3,4,5,6-pentahydroxy-2-hexanone.

Mechanisms of Renal Dysfunction

Oxidative stress is defined as an imbalance between prooxidants and antioxidants. Reactive oxygen species (ROS) are intermediary metabolites that are normally produced in the course of oxygen metabolism. There are many reactive oxygen species that are produced by all cell types and can have profound effects on the vascular system to impact blood pressure regulation. Oxidative stress increases during hypertension due to increased production of ROS such as superoxide, hydroxy radical, and hydrogen peroxide and or decreased superoxide dismutase (SOD), which scavenges ROS. Most recent attention has been given to the role of superoxide. There are many enzymatic sources of superoxide including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, nitric oxide synthase, and cytochrome P450. ROS can react with and denature proteins, lipids, nucleic acids, carbohydrates, and other molecules leading to inflammation, apoptosis, fibrosis, and cell proliferation. However,...

Capillary Isotachophoresis cITP

The most commonly employed chiral selector in CE is cyclodextrin, ring shaped carbohydrates made up of 6, 7, or 8 D-glucose subunits. Cyclodextrins may be chemically modified to alter their hydrophobicity or charge. Uncharged cyclodextrins are not suitable for the analysis of uncharged analytes since the complex will move with the EOF. However, cyclodextrins modified to carry a charge by addition of sulfate groups, can serve both as chiral selectors and as carrier molecules (similar to the detergent in MEKC). Other molecules, such as the antibiotic vancomycin, have also been employed as chiral selectors.

Deciphering the Sugar Codes for Selective Viral Entry of Host Cells Influenza A

The specificity of a variety of HAs toward carbohydrates containing sialic acid residues attached via a2-3, a2-6, and a2-8 linkages was screened using a glycan array. The assay showed that specific mutations control the specificity of a given HA that selectively binds to a given linkage. The microarray could also be used to probe the effect of charge, size, sulfation, fucosy-lation, and sialylation on the binding specificity. The binding specificity between two previous pandemic strains of HA, 18NY and 18SC, could be distinguished by the microarray since the 18NY recognizes both a2-6 and a2-3 linkages whereas 18SC recognizes only a2-6 linkages. Only two mutations are required to make the avian strain sufficiently virulent toward humans. This study illustrates an example that glycan array analysis, in conjunction with mutation studies, helps in understanding and predicting how pathogenic strains can become virulent toward humans.

Proteoglycans and Mucins

(3) epitopes expressed only on glycoproteins. To the first group belongs the lacto-series structure that is found in the most common human cancers, such as lung, breast, colorectal, liver, and pancreatic cancers. The common backbone structure for these epitopes is Ga1p1 3G1cNAcp1 3Ga1 (type 1 blood group) or Ga1p1 4 GlcNac p1 3 Gal (type 2 blood group). The second group of epitopes, expressed exclusively on gly-colipids, is mostly on the ganglio- or globo-series structures. This series of epitopes is expressed abundantly only on certain types of human cancers, such as melanoma, neuroblastoma, small cell lung carcinoma, and Burkitt's lymphoma. The third group of epitopes, seen only on glycoproteins, consists of the multiantennary branches of N-linked carbohydrates and the alterations of O-linked carbohydrate chains seen in some mucins.

Carbohydrate Antigens and Vaccines

The highly specific biological functions of carbohydrates were recognized by Heidelberger (144) from his studies on the capsular antigens of different strains of Streptococcus pneumoniae. These were not proteins, but turned out to be poly-saccharides. The antigen of the type 3 strain proved to be a polysaccharide having a disaccharide repeating unit 4)-p-D-Glcp-(1 3)-p-D-GlcpA-(1 (145). The factors responsible for the ABO human blood groups were shown by Morgan and Watkins (146) to be oligosaccharide components of various glycoconjugates built from a disaccharide a-L-Fucp-(1 2)-p-D-Galp-(1 (H factor) to which an a-D-GalpNAc group is linked (1 3) to the Galp component (A factor) or an a-D-Galp group is similarly linked (B factor). These studies opened up a large field of study of the interactions of carbohydrates and proteins, of major importance in pharmacology and medicine as it relates to antigen-antibody interactions, cell-cell recognition phenomena, and the fixation of bacteria,...

Diverse Biological Roles of Glycans

Glycans play key roles in protein folding, biological lifetime, recognition of binding pattern, cancer metastasis, signaling, and the immune system (7). For example, surface carbohydrates provide the interface between the cell and its environment, and serve to define self versus nonself. Many pathogens recognize particular cell surface carbohydrates, and structural studies have recently led to progress in this field (4). Glycans can serve as intermediates in generating energy, as signaling molecules, or as structural components. For example, the structural roles of glycans become particularly important in constructing complex multicellular organs and organisms, through steps which require interactions of cells with one another and surrounding matrix (8).

Carbohydrate Synthesis

Although it is possible to obtain carbohydrates through isolation from natural sources, it is exceedingly difficult to isolate adequate quantities of structurally homogeneous material, as carbohydrates often exist in living systems as difficult-to-separate heterogeneic mixtures. For the purposes of rigorous and controlled evaluation of the immunologic properties of tumor-associated carbohydrate antigens, it would clearly be advantageous to have access to single, homogeneous glycoforms. Our laboratory has long been devoted to the development of novel and improved methods for the de novo synthesis of structurally homogeneous carbohydrates and glycopeptides.

General Elucidation of Carbohydrate Structure

The chemistry and biochemistry of carbohydrates in general is detailed in a four-volume series (31), and a comprehensive treatment of polysaccharides can be found in the three volumes edited by Aspinall (32). A multiauthored treatise on polysaccharides published in 2005 (33) covers a wide range of aspects of the structural diversity, biological relevance, and technological applications of polysac-charides. A volume in the series Comprehensive Natural Product Chemistry edited by Pinto (34) provides extensive detail on the biosynthesis and biological role of carbohydrates.

Carbohydrate Microarrays as Essential Tools in the Postgenomics

In the past few years, a number of experimental approaches have been applied to construct carbohydrate microarrays (1,21,25,32,46,64,67,68,70). In spite of their technological differences, these carbohydrate microarrays are all solid-phase binding assays for carbohydrates and their interactions with other biological molecules. They share a number of common characteristics and technical advantages. First, they contain the capacity to display a large panel of carbohydrates in a limited chip space. Second, each carbohydrate is spotted in an amount that is drastically smaller than that required for a conventional molecular or immunological assay. Thus, the bioarray platform makes an effective use of carbohydrate substances. Third, they have high detection sensitivity. The microarray-based assays have higher detection sensitivity than most conventional molecular and immunological assays. This was attributed to the fact that the binding of a molecule in solution phase to an immobilized...

Lectincarbohydrate recognition general

Nature seems able to construct saccharide-binding sites on very different frameworks, as exemplified by the legume lectins with their large P structures and low cysteine content on one hand, and WGA (cereal lectin) with its high cysteine content and virtual absence of regular structures on the other. Chemical groups involved directly in binding are diverse. Carbohydrates interact with lectins through hydrogen bonds, metal coordination (metal-dependent lectins), van der Waals and hydrophobic interactions. The contributions of these chemical interactions in carbohydrate-lectin recognition (Weis and Drickamer, 1996) will be considered. Hydrogen bonding. The availability of a large number of hydroxyl groups on carbohydrates renders them obvious partners in complex networks of hydrogen bonds, usually formed by cooperative hydrogen bonds in which the hydroxyl serves both as a donor and an acceptor. Cooperative hydrogen bonding is characteristic of the interaction of lectins with...

B XRay Crystallography

Some of the earliest X-ray crystallographic studies on carbohydrates were conducted on oriented fibers of cellulose, and they demonstrated four hexopyranose rings in a monoclinic unit cell (103). A key crystallographic study on a small sugar molecule was that performed by Cox and Jeffrey (104) on a-D-glucosamine hydro-bromide, undertaken to settle the controversy as to the orientation of the amino group at C-2. Not only was this point resolved, but the three-dimensional architecture of the nonhydrogen atoms in the unit cell clearly demonstrated the familiar 4C1 chair conformation of the pyranose ring and the axial orientation of the hydroxyl group at C-1, long before the advent of NMR spectroscopy. The computational burden of manually resolving the diffraction data was enormous in early work, but the introduction of digital computers has greatly facilitated the task to the point that the three-dimensional structure of most sugar derivatives for which a small single crystal is...

Electrospray Ionization

John Fenn, who shared the Nobel Prize in Chemistry in 2002, developed the methodology for ESI MS of large and fragile polar biomolecules (15,16). Note that a simultaneous development occurred in Russia (17), although it was not well known at the time. ESI is an atmospheric pressure ionization technique now widely used for analysis of peptides, proteins, carbohydrates, and so on. It produces gaseous ionized molecules directly from a liquid solution (Fig. 5). During ESI, the sample solution continuously flows through a charged metal capillary, to which a potential difference (usually 3-5 kV) is applied to the tip and the surrounding atmospheric region. This potential difference can disperse the solution into a fine spray of charged droplets. At the same time, a flow of dry inert gas is introduced to the droplets at atmospheric pressure, resulting in the evaporation of solvent from each droplet, leaving the charged macromolecules as gas phase ions. Samples are usually prepared in a...

Further descriptive information

Arhodomonas aquaeolei is one of the few purely chemotrophic bacteria known that is phylogenetically related to the phototrophic purple sulfur bacteria of the Gammaproteobacteria and that belongs to the phylogenetic rather coherent group of the Ectothiorhodospiraceae. According to its 16S rDNA sequence, it is genetically most similar to Halorhodospira species but is sufficiently different so as to be recognized as a separate genus (Fig. BXII.y.19of the chapter describing the family Ectothiorhodospiraceae Imhoff and Suling, 1996). The characteristic loop at position 420 (UGCG) and the addition of C in the loop covering position 1361 are also present in the sequence of Arhodomonas aquaeolei (Adkins et al., 1993). Arhodomonas shares both the requirement for high salt concentrations and the restricted spectrum of carbon sources used with Halorhodospira and Ectothiorhodospira species (Imhoff, 1989). Most carbohydrates do not support growth, but other simple organic compounds are used...

Bsdspage and Western Blotting

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis SDS-PAGE (351) and the subsequent development of Western blotting are now routine methods of detecting cell proteins and carbohydrates. The former method separates a mixture of soluble biological molecules by mass to charge ratio, whereas the latter method allows for the transfer of proteins carbohydrates onto a membrane that is probed with a chosen antibody specific to that antigen. Application of an appropriate secondary sandwich-tagging antibody (e.g., if the first antibody has been sourced from rabbit sera, then the second antibody should be antirabbit) conjugated with an enzyme such as horseradish peroxidase (HRP) or alkaline phosphatase (AP), is used to detect the molecule of interest upon addition of a substrate for the enzyme that produces a colorimetric, fluorescent, or chemiluminescent signal at the separated protein band on the membrane.

Saccharide Biosynthesis And Glycobiology

Carbohydrates are of central significance in the balance between the Earth's 'living' and 'nonliving' carbon, since photosynthesis (Foyer, 1984), which leads primarily to neutral monosaccharides, is largely responsible for reversing the flow from nonliving to living occurring as a result of the normal process of life. At the center of carbohydrate metabolism is D-Glucose (Glc). Once Glc has been formed, different derivatives from the phosphate esters take over the role of providing the driving force for the reactions by which monosaccharides interconvert (Figure 13.1), leading to biosyntheses of oligo- and polysaccharides.

Endosomes And Lysosomes

Major functions of the Golgi apparatus are to modify proteins and synthesize carbohydrates. Proteins are preliminarily modified in the ER by the addition of oligosaccharides. When transported to the Golgi apparatus, the proteins are further processed by glycosylation, or the addition of complex oligosaccharides and high-mannose-content oligosaccharides. The glycosylation process, which occurs through the Golgi cisternae, is critical to the formation of glycolproteins. In addition, the Golgi apparatus assembles proteoglycans, a process involving the polymerization of glycosaminoglycans (GAG) and the linkage of GAG chains to core proteins. Proteoglycans are deployed to the extracellular space and serve as ground substance. It is important to note that lipid vesicles can bud from the Golgi network and cisternae. These vesicles play a critical role for the transport of proteins between the Golgi subsystems and from the Golgi apparatus to destination compartments. The citric cycle, also...

Monosaccharide Structure

N-Acetylneuraminic acid (46) was isolated by Gottschalk (47) from glycoproteins by the action of an enzyme (sialidase) from influenza virus, and was recognized as part of a group of related nine-carbon sugars (48). Encountered as a component of certain oligosaccharides of human milk (see Chapter 12) in the extensive researches of Richard Kuhn (49), the broad significance of this unusual sugar in biological processes (50) as a key feature of cell-surface carbohydrates continues to unfold, especially in its role as a component of the tetrasaccharide determinants (sialyl-Lewisx and sialyl-Lewisa) involved in cell adhesion and the inflammatory response (51). The eight-carbon sugar Kdo is a component of the core region of the complex cell-surface lipopolysaccharides of Gram-negative bacteria, serving to link the endotoxin lipid A to the remainder of the carbohydrate component (52,53).

Identification of Immunogenic Sugar Moieties of B anthracis Exosporium

A photogenerated oligosaccharide array was introduced to facilitate identification and characterization of anthrax spore-specific immunogenic carbohydrate moieties (64). In essence, the authors utilized a photoactive surface on glass substrates for covalent immobilization and micropatterning of carbohydrates (7). They then applied this glycan array to probe specific antibodies that were elicited by immunizations using anthrax spores. The authors assumed that if B. anthracis spores express potent immunogenic carbohydrate moieties, immunization with the spores would elicit antibodies specific for these sugar structures. Such antibody reactivities would then be detected by glycan arrays that display the corresponding sugar structures. A schematic overview of this biomarker identification strategy is shown in Fig. 2. Figure 2 Photogenerated glycan arrays for rapid identification of pathogen-specific immunogenic sugar moieties. Saccharide preparations were dissolved in saline (0.9 NaCl) at...

Convergent Synthesis of a GPI with 2OAcylated Inositol

In the synthesis of sperm CD52 GPI anchor that contains a 2-O-acylated inositol, we met a special problem. The presence of a large acyl group at the inositol 2-O-position adds more steric hindrance to the already rather crowded structure of GPIs around the inositol residue. Therefore, the traditional synthetic design, namely, to introduce the phospholipid moiety to the inositol 1-O-position at the final stage failed, and a new synthetic design was developed to solve the problem (106). This is a good manifestation that presently there is not a universally applicable synthetic design for all carbohydrates and that the synthesis of each oligosac-charide must be treated as an individual challenge with the synthesis planned accordingly, even when there are precedent syntheses of similar structures.

Controversial Health Benefits of Low Carbohydrate and High Beef Diets

The recent epidemic of obesity in Western countries has contributed to the dramatic increase in the popularity of low-carbohydrate diets, such as the Atkins (56), South Beach (57), and Protein Power diets (58). This rapid switch in dietary habits has had a profound effect on the food industry, despite the opposition from the majority of the nutrition establishment (29). Recently, some nutrition professionals have argued for the need to understand the apparent success of low-carbohydrate diets in some studies (59), but little work has been done in this area. Feinman and Fine have argued that low-carbohydrate diets have a metabolic advantage because proteins require metabolic energy to convert them to carbohydrates (60). One component of the inefficiency in metabolizing food is measured by ther-mogenesis (thermic effect of feeding), or the heat generated during the metabolism of food. As summarized in a recent review by Jequier (61), the thermic effects of nutrients is 2-3 for lipids,...

Recognition of Autoimmunogenic Reactivity of SARSCoV

The first step, microarray analysis, revealed that immunization of horses with a preparation of inactivated SARS-CoV induced antibodies specific for an abundant human glycoprotein asialo-orosomucoid (ASOR). Since the horse antisera has no reactivity toward agalacto-orosomucoid (AGOR), which lacks galactose in the upper stream nonreducing ends, the glycoepitopes with terminal galactose may contribute significantly to the antigenic reactivity of SARS-CoV. This glycan array finding gave an important lead in terms of identifying appropriate immuno-logical probes to further characterize the glycoepitopes expressed by SARS-CoV. A microarray containing a panel of galactose-containing complex carbohydrates was created to scan for immunological probes specific for the ASOR-glycans. The lectin PHA-L was shown to be highly specific for the spotted ASOR preparation. The latter is known to be specific for the glycoepitopes that are composed of tri-antennary Galp1-4GlcNAc (Tri-II) or multiantennary...

High Fat Diets Decrease Longevity in Drosophila

However, the specific mechanism responsible for the deleterious effects of saturated fats is unknown. One of the first studies that attempted to make a connection between Drosophila dietary components and longevity found that isocaloric diets consisting of high saturated fats (such as palmitic acid) and low carbohydrates will, on average, shorten the life span of Drosophila compared with flies fed control diets high in carbohydrates and low in saturated fats (24-26). These early studies, performed in the late 1970s and early 1980s by Driver and colleagues (24-26), did not determine the specific metabolic processes that were negatively affected by the consumption of fat. Instead, they potentially laid the groundwork for further studies.

Glycomics Proteoglycomic Approaches

Hydrazide covalent conjugation (Zhang et al., 2003) Periodate oxidation converts the cis-diols of carbohydrates to aldehydes, which form covalent hydrazone bonds with the hydrazide (or amine) groups immobilized on the solid support. After washing removing the nonglycosylated proteins, the immobilized glycoproteins are proteolyzed on the solid support. Nonglycosylated peptides are again washed away while the glycosylated peptides remain on the solid support. The a-amino groups of the immobilized glycopeptides are then labeled with isotopically light (H) and heavy (D)-succinic anhydride after lysine residues have been converted to homoarginine termed stable isotope tagging. The N-glycosylated peptides are finally released from the solid support using peptide-N-glycosidase F (PNGF). The released peptides are identified quantified with MS-MS. Figure17.4 shows a schematic representation of hydrazide covalent isotope tagging.

Structure of antibody

Antibodies belong to the class of serum glycoproteins called immunoglobulins (Igs), which are made in all vertebrates as part of the immune response to antigenic challenge by foreign substances (van Oss and van Regenmortel, 1994). Immunoglobulins are Y-shaped proteins made up of two identical light (L) polypeptide chains (Mol. wt. 25 kDa) and two identical heavy (H) chains (mol. wt. 50kDa) held together by disulfide bonds. Immunoglobulins are divided into several major classes or isotypes characterized by their heavy (H) chain type (Table 10.4). They all contain carbohydrates, largely d-hexose and D-hexosamine but also sialic acid and L-fucose, covalently attached to protein moiety.

Nutrigenomics Research on Dietary Beef

A major component of many low-carbohydrate diets, such as the Atkins diet, is 95 lean ground beef, typified by a hamburger without the bun (56). Lean ground beef consists of 35 fat and 65 protein ( Kcal), in addition to 65 mg cholesterol and 55 mg sodium per 85 gram portion. The fat portion consists of approximately equal amounts of saturated and mono-unsaturated fats (FDA food label). Surprisingly, we could only find one previous study in which Drosophila were fed dietary beef (63), and one microarray study where mice were fed beef tallow (64). The Drosophila beef paper was published in 1979

Hereditary Neurometabolic Diseases

Lysosomal Diseases Peroxisomal Diseases Leukodystrophies Mitochondrial Diseases Amino Acid Metabolic Diseases Carbohydrates Metabolic Diseases Copper Metabolic Diseases Neuroaxonal Dystrophies Miscellaneous Neurometabolic Diseases Diseases caused by defective metabolism of amino acids, carbohydrates, and copper

Physiological Effects Of Glucocortioids

Cortisol, the main glucocorticoid present in circulation, is a carbohydrate-sparing hormone exerting an anti-insulin effect, which can lead to hypogly-cemia and insulin-resistance. In addition, glucocorticoids maintain blood glucose and the glycogen content of the liver by promoting the conversion of amino acids to carbohydrates and the storage of carbohydrate as hepatic glycogen. glucocorticoids may lead to increased ketosis, especially in patients with diabetes mellitus.

Conclusions And Perspectives

Combining CE with MS allows efficient separation and identification of important biological compounds, such as pharmaceuticals, carbohydrates, peptides, proteins, and glycoforms. As more instruments interfacing CE with MS become more available, the number of applications will continue to grow. However, since most of the published applications have used model compounds, future work should focus on real-life samples. Moreover, additional studies will be necessary to evaluate whether this technique fulfills the validation criteria recommended by official guidelines required for the quantification of drugs and metabolites. Widespread acceptance of CE-MS within the electrophoretic and chromatographic community, as well as clinical and forensic laboratories, can only be realized by achieving such objectives.

Preface to the Series

This series in heterocyclic chemistry is being introduced to collectively make available critically and comprehensively reviewed literature scattered in various journals as papers and review articles. All sorts of heterocyclic compounds originating from synthesis, natural products, marine products, insects, etc. will be covered. Several heterocyclic compounds play a significant role in maintaining life. Blood constituent hemoglobin and purines as well as pyrimidines, the constituents of nucleic acid (DNA and RNA) are also heterocyclic compounds. Several amino acids, carbohydrates, vitamins, alkaloids, antibiotics, etc. are also heterocyclic compounds that are essential for life. Heterocyclic compounds are widely used in clinical practice as drugs, but all applications of heterocyclic medicines can not be discussed in detail. In addition to such applications, heterocyclic compounds also find several applications in the plastics industry, in photography as sensitizers and developers,...

Mw 144 C6h7o2k Mw 150

Addition of the ingredients in the correct order is essential to avoid production problems. The normal order starts with the presence of around 30-50 of final product volume of process water to which preservatives other than sulphur dioxide are first added. This volume should be as large as possible to allow the addition of carbohydrates and fruit components, which follow in that order. At this point, the volume should be approaching 90 of final volume to allow the dilution of preservatives. Acidulant is then added, followed by colourings, flavourings and all other components.

Apoptosis of Macrophages

While apoptosis of vascular SMCs characterizes early plaque growth apoptosis of these cells has also been demonstrated in fibrotic part of advanced human atheromata (20) and SMC apoptosis may also contribute to plaque vulnerability by recruitment of inflammation via Fas-associated death domain (FADD) protein induced expression of MCP-1 and interleukin-8 (IL-8) causing migration of macrophages (21). However, apoptosis of smooth muscle cells plays a minor role in undermining plaque stability compared to apoptosis of macrophages. Using human autopsy material Kolodgie and coinvestigators defined culprit plaque as plaque rupture with intralumenal thrombosis and stable plaque as stenotic lesions with thick fibrous cap (13). Ruptured plaque showed extensive infiltration of macrophages that stained positive for caspase-1, a mammalian death protease while the stable lesions showed a dense fibrous cap with paucity of apoptotic cells (13). This same group of investigators went on to target...

Nutritional Supplementation

McCrory et al. found that a wide variety of sweets, snacks, condiments, and high-carbohydrate entrees coupled with a smaller variety of vegetables promoted long-term increase in energy intake and body fat 17 . Providing nutritional supplements consisting of a wide variety of sweets and carbohydrates may be helpful as the second step for the treatment of weight loss. In addition, loss of taste and smell are common in the elderly, and medications and medical conditions play a major role in taste losses and distortions 18 . Thus, the use of flavour-enhanced food has a correspondingly positive effect on food intake.

Achieving Balance between Acidity and Alkalinity

As discussed in Chapter 21, the ketogenic diet consists of high fat and low protein, low carbohydrate foods. The goal of the diet is twofold by forcing the patient to burn fat as fuel instead of carbohydrates, by-products known as ketone bodies (such as acetone) are produced. As a result, an acidic environment is created in the patient by metabolic aci-dosis. This diet can be beneficial, especially if it can be shown that the patient was previously in an alkaline state or had alkalosis (7).

The Krebs Cycle The Central Switching Yard Of Metabolism

The fuels we take in in the diet are mainly fats, proteins, and carbohydrates. At the very center of metabolism is a cycle of reactions that takes place in the mitochondrial matrix. The cycle is named after its discoverer, Hans Krebs, and is also known as the tricarboxylic acid (TCA) cycle or the citric acid cycle. The foods we eat are converted to the two-carbon unit acetate, CH3COO-. The acetate is not free but is carried by a coenzyme called coenzyme A. Acetate bound to coenzyme A acetyl-CoA for short is then fed into the Krebs cycle and may be completely oxidized to carbon dioxide and water. In the process the energy currency NADH is produced. The Krebs cycle is central to carbohydrate, fat, and amino acid metabolism.

Traditional Approaches to Seizure Disorders

I am not a neurologist, neurosurgeon, or epileptologist. When the first child with a major seizure disorder was brought to me many years ago, I had no idea what osteopath-ic principles and practice could accomplish concerning the seizures, but I knew that their application would enable the child to function closer to the optimum of his potential. Since that early challenge, I have treated approximately 90 children, whose records were retrospectively studied. Every type of seizure was observed. The various therapeutic measures these children received included ACTH in early infancy, the whole spectrum of AEDs, the ketogenic diet, the vagus nerve stimulator, and brain surgery. A search of the literature reveals that all these modalities help many children, but many still remain who live with the insecurity and uncertainty of unpredictable seizures. These children find their way to the OCC. We know the children whose neurologic development was arrested never to get back on track after...

Micronutrients in the Diets of Industrialized Countries

In the USA and Western Europe, agriculture and the food industry produce enough to feed the population and export large quantities of food. Despite this, many people are poorly nourished they are oversupplied with foods rich in fat, protein, sugar, and salt, and under-supplied with complex carbohydrates, fiber, vitamins, and minerals. Dietary surveys have repeatedly found that micronutrient deficiencies are widespread in the industrialized countries. For example

Energy Distribution Among Nutrients

However, in addition to the importance of controlling the total amount of dietary energy, food choices should be directed towards a balanced distribution of energy among nutrient sources. Epidemiological and experimental studies have led to the establishment of correct energy distribution among carbohydrates, fats, and protein, in order to prevent the onset of chronic diseases and to assure the maintenance of a good nutritional and health status. In this view, in the USA, more than 20 years ago, a Senate Select Committee stated that the energy distribution compatible with good health and that should be reached by the American population (dietary goals) should consist of 58 of energy from carbohydrates, 30 from fats, and 12 from proteins. Among carbohydrates, 15 of calories should derive from sugars and 40-50 from complex carbohydrates, while, among fats, 10 of calories should come from saturated fats and 20 from unsaturated fats 13 . carbohydrates and fats. For carbohydrates, there is...

Mechanisms of Malnutrition in Chronic Pancreatitis

Muscle Loss Malnutrition Exam

Nar cells causes insufficient secretion of lipase, col-ipase, amylase, and proteases, which results in maldigestion of lipid, carbohydrates, and protein. Of these nutrients, fat maldigestion is the most clinically apparent. However, because the pancreas secretes a large surplus of enzymes, pancreatic enzyme output must be reduced to less than 10 of normal before fat absorption is appreciably impaired. Fat digestion depends not only on the amount of pancreatic lipase and colipase, but also on the activity of these enzymes. Since lipase has maximal enzymatic activity in the range of pH 6.5-8, decreased bicarbonate delivery to the duodenum leads to inactivation of lipase through a pH drop. In addition, since duodenal acidification precipitates bile salts, mixed micelle formation is impaired, resulting in the malabsorption of fat. All these pathophysiological events contribute to massive steatorrhoea, leading to malnutrition and weight loss in chronic pancreatitis patients.

Carbohydrate in Wound Healing Modulation

Because of the vast number and range of carbohydrates, it is not surprising that there are well-established examples of carbohydrates that are applied to patients not as a dressing but as a means to change the biological processes of wound healing. In this section, we look at two such clinical applications, honey and heparin. These provide an interesting comparison that illustrates the complexities of evidence in clinical medicine. There is no doubt that honey has been used for many thousands of years and that there are many papers reporting clinical outcomes. Nevertheless, honey is a complex chemical compound. Being a natural product of such complexity, it is understandable that there will be variations in the nature and efficacy of the product, no matter how much care and attention is made to keep conditions of preparation, extraction, and production constant. The analogy would be in wine production and even the most inexperienced enol-ogist will appreciate the wide variations in...

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