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. Read more here...

Keto Resource Summary


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Currently Available Prebiotic Carbohydrates

Evidence that some dietary fibers, such as resistant starches (66-72), arabinoxylan (73,74) and plant gums (75) have prebiotic potential is accumulating, but to date remains limited largely to in vitro and animal studies. These large carbohydrates may have some advantages in the intestinal tract over rapidly fermented oligosaccharides. They minimize rapid gas formation and osmotic effects in the gut, which can lead to intestinal discomfort, flatulence and diarrhea at high doses of NDOs (typically above 15-20 g per day). Additionally, they persist as substrates for saccharolytic fermentation more distally in the colon where carbohydrate limitation is believed to promote toxigenic microbial reactions leading to an increased risk of colorectal cancer (76-79). The molecular structure of the prebiotic can be expected to determine its physiological effects as well as which microbial species are able to utilize it as a carbon and energy source in the bowel. However, it appears that despite...

Digestion Absorption Of Carbohydrates

The digestion of complex carbohydrates is by hydrolysis to liberate oligosaccharides, then free mono- and di-saccharides. The increase in blood glucose after a test dose of a carbohydrate compared with that after an equivalent amount of glucose is known as the glycemic index. Glucose and galactose have an index of 1, as do lactose, maltose, isomaltose, and trehalose, which give rise to these monosaccharides on hydrolysis. Fructose and the sugar alcohols are absorbed less rapidly and have a lower glycemic index, as does sucrose. The glycemic index of starch varies between near 1 to near zero due to variable rates of hydrolysis, and that of non-starch polysaccharides is zero. Foods that have a low glycemic index are considered to be more beneficial since they cause less fluctuation in insulin secretion.

Macronutrients Carbohydrates Insoluble Solids and Lipids

Plants contribute to the availability of dietary macronutrients including protein, fats, and carbohydrates. A large amount of data exists for these macronutrients in agronomic crops wherein these well-characterized constituents are significant crop yield components. In tomato, these constituents have been studied principally for their effects on fruit quality. Little attention has been given to their contribution to fruit nutritive value. Modification of plant carbohydrate composition is a research area receiving closer scrutiny in light of the positive effects that fiber and complex carbohydrates can have on aspects of human health such as lipid metabolism and diabetes (Anderson 1990). Dietary plant fibers are derived from plant structural components and include both water-soluble and water-insoluble nonstarch polysaccharides and lignin. Genetic variability for the type and amount of soluble carbohydrates, pectin, gum, lignin, and other fiber components exists within tomato.

Carbohydrates Are Aldehyde Or Ketone Derivatives Of Polyhydric Alcohols

(1) Monosaccharides are those carbohydrates that cannot be hydrolyzed into simpler carbohydrates They may be classified as trioses, tetroses, pentoses, hex-oses, or heptoses, depending upon the number of carbon atoms and as aldoses or ketoses depending upon whether they have an aldehyde or ketone group. Examples are listed in Table 13-1.

Carbohydrates and mental health

Carbohydrates include starches, naturally occurring and refined sugars, and dietary fiber. Foods rich in starches and dietary fiber include grain products like breads, rice, pasta and cereals, especially whole-grain products fruits and vegetables, especially starchy vegetables like potatoes. Foods rich in refined sugars include cakes, cookies, desserts, candy, and soft drinks. Carbohydrates significantly affect mood and behavior. Eating a meal high in carbohydrates triggers release of a hormone called insulin in the body. Insulin helps let

Blurring the Distinctions Between Prebiotics Dietary Fibers and Other Fermentable Dietary Carbohydrates in the Colon

The greatest volume of research and evidence for prebiotic effects has been accrued for fructo-oligosaccharides and inulin, but there is accumulating evidence of prebiotic actions by a number of non-digestible carbohydrates. Lactulose and galacto-oligosaccharides have strong claims to be classified as prebiotics, while there is promising evidence for prebiotic activity by isomalto-, xylo-, and soybean-oligosaccharides. There is growing interest in the impact of dietary fibers on the composition as well as the activity of the intestinal microbiota, and resistant starches and arabinoxylans in particular warrant further study for bifidogenic and other prebiotic effects.

Carbohydrates Occur In Cell Membranes In Lipoproteins

In addition to the lipid of cell membranes (see Chapters 14 and 41), approximately 5 is carbohydrate in glyco-proteins and glycolipids. Carbohydrates are also present in apo B of lipoproteins. Their presence on the outer surface of the plasma membrane (the glycocalyx) has been shown with the use of plant lectins, protein agglutinins that bind with specific glycosyl residues. For example, concanavalin A binds a-glucosyl and a-man-nosyl residues. Glycophorin is a major integral membrane glycoprotein of human erythrocytes and spans the lipid membrane, having free polypeptide portions

Assays to Identify a Sweet Pill in a Library of Carbohydrates Mark E Beauharnois Sriram Neelamegham and Khushi L Matta

Soluble oligosaccharides and glycoproteins can inhibit leukocyte adhesion during a range of vascular ailments including inflammation, thrombosis, and cancer metastasis. The design of such molecules in many cases is based on the structure of naturally occurring selectin ligands. In this case, synthetic selectin-ligand mimetics act as competitive inhibitors of cell adhesion. In an alternate approach, cell-permeable, small-molecule oligosaccharides have been shown to alter the metabolic pathways that lead to the biosynthesis of functional selectin-ligands. The addition of such molecules results in glycoproteins that are defective in their ability to bind selectins. Quantitative in vitro testing of the efficacy of the above inhibition strategies ideally requires the application of assays that mimic the in vivo physiological milieu in terms of the valency of selectin and selectin-ligands, the physiological fluid-flow conditions, and the use of blood cells. Assays that are performed in...

Sugars and carbohydrates

Carbohydrates are found in simple sugars, as constituents of glycoproteins and glycolipids, and in polymeric form as structural features of bacterial and fungal cell walls, among other sources. Polymeric sugars include dextran, used as a blood expander, and starch. Sugars are most commonly analyzed by ion-exchange or other chromatographies, since they tend to be so hydro-philic as to elute rapidly from reversed phase columns. N-butyldeoxynojir-imycin, deoxynojirimycin, and their degradation products were separated on a Zorbax C8 Rx column in water acetonitrile containing heptane sulfonate and acetic acid.88 The amino sugars mannosamine, galactosamine, and glucosamine extracted from tobacco were derivatized with o-phthalde-hyde and analyzed in THF (tetrahydro furan) water on C18.89 Another deriva-tization agent, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, available commercially as AccQ-Tag , has been used for amino sugars such as a- and P-galactosamine and a- and P-glucosamine in...


Carbohydrates (kar bo-hi'dratz) provide much of the energy that cells require. They also supply materials to build certain cell structures, and they often are stored as reserve energy supplies. Carbohydrates are water-soluble molecules that contain atoms of carbon, hydrogen, and oxygen. These molecules usually have twice as many hydrogen as oxygen atoms, the same ratio of hydrogen to oxygen as in water molecules (H2O). This ratio is easy to see in the molecular formulas of the carbohydrates glucose (CbH Ob) and sucrose (C12H22O11). Carbohydrates are classified by size. Simple carbohydrates, or sugars, include the monosaccharides (single sugars) and disaccharides (double sugars). A monosac-charide may include from three to seven carbon atoms, occurring in a straight chain or a ring (fig. 2.10). Mono-saccharides include glucose (dextrose), fructose, and galactose. Disaccharides consist of two 6-carbon units. Sucrose (table sugar) and lactose (milk sugar) are disac-charides (fig. 2.11a...

Michael A Morse MD Timothy M Clay PhD and H Kim Lyerly MD

B cells recognize tumor antigen as epitopes on proteins or carbohydrates via the B-cell receptor, a surface-expressed, monospecific immunoglobulin. Although B cells can be directly activated by large antigens that bind simultaneously to multiple antibody receptors, this T-cell-independent activation results in mainly IgM production and poor memory induction. T-cell-dependent responses, in contrast, usually require two signals for activation, antigen binding to the B-cell receptor and cytokine secretion from Th cells. Antigen either binds to the B-cell receptor or is presented to B cells by APCs such as macrophages or follicular DCs. Antigen is also processed by APCs and presented to Th cells. Furthermore, antigen taken up by B cells can be processed and presented to Th cells via MHC class II molecules. The Th cells supply IL-2, IL-4, IL-5, and CD40-ligand that As described above, although most tumors appear to be nonimmunogenic, they in fact express antigens, either native,...

Feeding ecology and diet

Primate species exhibit a wide range of diets, although most of them include at least some fruits in their food intake. If there is a typical dietary category for primates generally, it is surely fruit consumption, as this is found from the smallest to the largest species. Although most primates eat at least some fruits, primates can be classified into three main dietary categories representing at least 50 of food intake (1) insectivores, feeding mainly on arthropods (e.g., tarsiers) (2) frugivores, feeding mainly on fruits (e.g., most forest-living monkeys) (3) folivores, feeding mainly on leaves (e.g., leaf-monkeys). There is a general trend among primates for the diet to shift progressively from insectivory through frugivory to folivory as body size increases. This is understandable because small-bodied mammals have relatively high-energy requirements per unit body weight and must eat foods with a rich, easily available energy content. Large-bodied mammals have relatively low...

Role Of The Gastrointestinal Microbiota In Humans

Traditionally, the colon has been considered to largely be the human sewage system which, as well as storing and removing waste material from the GI tract, was capable of recycling water (i.e., absorption). However, we now recognize that the GI tract is one of the most metabolically and immunologically active organs of the human body. Indeed, the primary function of the microbiota is generally considered to be salvage of energy via fermentation of carbohydrates, such as indigestible dietary residues (plant cell walls, non-digestible fibers and oligosaccharides), mucin side-chains and sloughed-off epithelial cells (5,6,8,13,17). It has been estimated that between 20 and 60 grams of carbohydrate are available in the colon of healthy human adults per day, as well as 5-20 grams of protein. In addition to salvaging energy, principally through production of short-chain fatty acids (SCFAs) and their subsequent absorption and use by the host, microbial fermentation produces gases (principally...

Biomedical Importance

Water is the predominant chemical component of living organisms. Its unique physical properties, which include the ability to solvate a wide range of organic and inorganic molecules, derive from water's dipolar structure and exceptional capacity for forming hydrogen bonds. The manner in which water interacts with a sol-vated biomolecule influences the structure of each. An excellent nucleophile, water is a reactant or product in many metabolic reactions. Water has a slight propensity to dissociate into hydroxide ions and protons. The acidity of aqueous solutions is generally reported using the logarithmic pH scale. Bicarbonate and other buffers normally maintain the pH of extracellular fluid between 7.35 and 7.45. Suspected disturbances of acid-base balance are verified by measuring the pH of arterial blood and the CO2 content of venous blood. Causes of acidosis (blood pH 7.35) include diabetic ketosis and lactic acidosis. Alkalosis (pH 7.45) may, for example, follow vomiting of...

Nonradioactive Trans Sialidase Screening Assay Silke Schrader and Roland Schauer

Trans-sialidase (TS E.C. catalyzes the transfer of preferably a2,3-linked sialic acid to another glycan or glycoconjugate, forming a new a2,3-linkage to galactose or N-acetyl-galactosamine. In the absence of an appropriate acceptor, TS acts as a sialidase, hydrolyti-cally releasing glycosidically linked sialic acid. Interest in TS has increased rapidly in recent years owing to its great relevance to the pathogenicity of trypanosomes and its possible application in the regiospecific synthesis of sialylated carbohydrates and glycoconjugates. Recently, the authors described a newly developed nonradioactive screening test for monitoring TS activity (1). In this highly sensitive and specific assay, 4-methylumbelliferyl-P-d-galactoside is used as acceptor substrate and sialyllactose as donor to fluorimetrically detect enzyme activity in the low mU range ( 0.1-1 mU mL possible). The test can be applied to screen a large number of samples quickly and reliably during enzyme...

What Do Chronologically Aged Cells Die From

Entry of yeast cells into stationary phase is accompanied by a starvation response in which storage carbohydrates, such as glycogen and trehalose, are synthesized and maintained at high levels in the cytoplasm (Gray et al., 2004). Storage carbohydrates serve as the main source of energy production during stationary phase (Fabrizio and Longo, 2003) and adequate production of storage carbohydrates is essential for long-term survival. Interestingly, some chronologically long-lived mutants show dramatically increased glycogen stores, even under logarithmic growth conditions, suggesting that depletion of reserve carbohydrates might be one factor resulting in cell death. This idea is supported by one study in which intracellular glycogen and trehalose levels were reported

Postnatal development

Species is quite closely reflected in milk composition. Three principal components of mammalian milk are carbohydrates, fats, and proteins. As a crude approximation, it can be said that the carbohydrate content of milk reflects immediate energy needs of the offspring, while the fat content indicates energy needs over a longer term. The protein content of milk provides a fairly good indication of requirements for growth. Milk composition also provides an indication of maternal behavior. Here, a major distinction can be drawn between mothers that feed on schedule and those that feed on demand. For offspring that are fed on schedule, it is the mother that determines the suckling frequency. Commonly, this applies to offspring that are left in a nest. These tend to be fast growing but relatively inactive altricial offspring that must maintain their body temperature unaided in the absence of the mother. As a result, the milk of such species tends to be high in protein and fat but relatively...

Lipid Receptors Peroxisome Proliferator Activated Receptors

Its function is not essential for survival as null homozygotes are phenotypically normal. However, these animals are insensitive to the actions of peroxisome proliferators and, when challenged with fasting or high-fat diets, experience perturbations in lipid and glucose homeosta-sis.388,389 These observations suggest that PPARa not only functions as a xenobiotic receptor but also may play a significant role in lipid home-ostasis in response to unknown physiological lig-ands.

Acquisition Of The Gut Microbiota

During the initial phase of acquisition, facultative anaerobes predominate (enterobacteria and streptococci) and effectively reduce the redox potential of the gut environment enabling colonization by obligate anaerobes (including bacteroides, bifidobacteria, clostridia, and eubacteria). Factors such as diet and host genetics play important roles in the development of the microbiota (with some bacterial populations eliminated and others maintained) (3,24). The classical studies by Tissier almost a century ago first highlighted the significant difference of the fecal microbiota harbored by breastfed and formula-fed infants. Indeed, Tissier described three phases of microbial acquisition in infants 1, initial hours of life when the fecal bacterial content was nil 2, beginning between the tenth and twentieth hour of life, comprising a heterogeneous microbiota 3, after passage of maternal milk through the intestinal tract, the microbiota being predominated by bifidobacteria (an obligately...

Prevention strategies whole populations highrisk groups or selected individuals

That second issue goes further than that. As Rose eloquently pointed out, those factors that best explain the occurrence of cases within a population may not best account for the rate of the disease within the population at large. For example, if the population, overall, consumes a high-fat diet, then whether or not an individual smokes cigarettes may best explain whether he she develops coronary heart disease. Meanwhile, the population-wide dietary behavior may be the main source of the elevated rate of coronary heart disease within that population. Consider another example, admittedly extreme, but it helps to make the point. If within a population everyone smoked 20 cigarettes per day, then the prime determinant of individual risk of lung cancer might well be one or more genetic polymorphisms which determine the fate of inhaled carcinogens. Yet it is the smoking that accounts for the overall high rate of lung cancer in that hapless population.

Clinical Aspects

The major pathophysiological abnormalities generated by diabetes mellitus include the following (i) glucose intolerance or inappropriately high blood glucose levels in the presence of elevated or normal insulin concentrations (ii) acidosis and ketosis (iii) reduction of the enzymes for gluconeogenesis (iv) reduced growth (v) a microangiopathy, including a thickened basement membrane of capillaries in muscle and retinal blood vessels and of the capillaries of the renal glomerulus and (vi) a neuropathy, including peripheral sensory and motor defects.

The Liver Plays A Central Role In Lipid Transport Metabolism

The cellular events involved in VLDL formation and secretion have been described above. Hepatic triacyl-glycerol synthesis provides the immediate stimulus for the formation and secretion of VLDL. The fatty acids used are derived from two possible sources (1) synthesis within the liver from acetyl-CoA derived mainly from carbohydrate (perhaps not so important in humans) and (2) uptake of free fatty acids from the circulation. The first source is predominant in the well-fed condition, when fatty acid synthesis is high and the level of circulating free fatty acids is low. As triacylglyc-erol does not normally accumulate in the liver under this condition, it must be inferred that it is transported from the liver in VLDL as rapidly as it is synthesized and that the synthesis of apo B-100 is not rate-limiting. Free fatty acids from the circulation are the main source during starvation, the feeding of high-fat diets, or in diabetes mellitus, when hepatic lipogenesis is inhibited. Factors...

Gluconeogenesis Control of the Blood Glucose

Glycogen Entering Glycolysis

Gluconeogenesis is the term used to include all pathways responsible for converting noncarbohydrate precursors to glucose or glycogen. The major substrates are the glucogenic amino acids and lactate, glycerol, and propionate. Liver and kidney are the major gluco-neogenic tissues. Gluconeogenesis meets the needs of the body for glucose when carbohydrate is not available in sufficient amounts from the diet or from glycogen reserves. A supply of glucose is necessary especially for the nervous system and erythrocytes. Failure of gluconeogenesis is usually fatal. Hypoglycemia causes brain dysfunction, which can lead to coma and death. Glucose is also important in maintaining the level of intermediates of the citric acid cycle even when fatty acids are the main source of acetyl-CoA in the tissues. In addition, gluconeogenesis clears lactate produced by muscle and erythrocytes and glycerol produced by adipose tissue. Propionate, the principal glucogenic fatty acid produced in the digestion...

Plate 49 Sublingual Gland

Saliva includes the combined secretions of all the major and minor salivary glands. The functions of saliva include moistening dry foods to aid swallowing, dissolving and suspending food materials that chemically stimulate taste buds, buffering the contents of the oral cavity through its high concentration of bicarbonate ion, digestion of carbohydrates by the digestive enzyme a-amylase (which breaks the 1-4 glycoside bonds and continues to act in the esophagus and stomach), and controlling the bacterial flora of the oral cavity because of the presence of the antibacterial enzyme lysozyme.

Retrieving and Analyzing GEO Data

A screen shot of a typical DataSet record, GDS279, which investigates the effect of a high-fat diet on liver tissue in wild-type and LDL receptor-deficient mice (6). The locations of the main DataSet features and tools are indicated. Fig. 1. GEO DataSet record. A screen shot of a typical DataSet record, GDS279, which investigates the effect of a high-fat diet on liver tissue in wild-type and LDL receptor-deficient mice (6). The locations of the main DataSet features and tools are indicated. Fig. 2. Screenshot of GEO Profiles retrievals and expanded profile chart. (A) Screen shot of GEO Profiles retrievals for GDS279, a DataSet that investigates the effect of a high-fat diet on liver tissue in wild-type and LDL receptor-deficient mice (6). Each retrieval represents an individual gene on the array. The locations of various features are indicated. (B) Expanded chart for the Cidec gene. The chart bars represent relative gene expression levels in each Sample...

Effect of Glycosylation Changes on the Interaction of Viral Envelope Glycoproteins With the Immune System

Carbohydrates are generally regarded as poorly immunogenic because (1) identical glycan epitopes are also found on host cell glycoproteins, thus are recognized as self by the immune system, (2) glycoproteins display considerable microheterogeneity, and (3) carbohydrates are extensive structures that may mask potential protein-based epitopes (22). Indeed the glycosylation of HIV gp120 is thought to act as an evolving glycan shield, whereby changes in N-glycosylation acceptor sites due to escape mutations in gp120 enable HIV to evade the host immune response by shielding underlying epitopes with variable glycosylation (23,24). Similarly, the acquisition of N-glycosylation sequons in the influenza H3 HA1 glycoprotein is also thought to protect from the binding of neutralizing antibodies (25). Recent studies of antibodies, produced in monkeys inoculated with SIV gp120 glycosylation mutants, indicate that N-linked glycosylation influences immunogenicity in addition to antigenicity (15).

Development Of Overweight

Some evidence from developing countries indicates an increase in overweight among stunted children, but this may be a spurious finding due to limitations in the indices used to define overweight and metabolic differences. As indicated in the first section of this chapter, indices used for evaluating relative weight, such as BMI and weight-for-height, do not directly measure body fat. In the case of stunted children, those with increased BMIs may have an excess of body fat, heavier bones, or larger muscles. On the other hand, metabolic defects may contribute. In Brazil, mild stunting was associated with the percentage of energy from fat and weight gain, suggesting that stunted children may be more susceptible to the effects of a high-fat diet than other children (90). Still another possibility is that stunted children may be more likely to have impaired fat oxidation (91). Evidence from a longitudinal study in Guatemala has shown that severely stunted children have increased abdominal...

Polysaccharides Serve Storage Structural Functions

Polysaccharides include the following physiologically important carbohydrates. Glycosaminoglycans (mucopolysaccharides) are complex carbohydrates characterized by their content of amino sugars and uronic acids. When these chains are attached to a protein molecule, the result is a pro-teoglycan. Proteoglycans provide the ground or packing substance of connective tissues. Their property of holding large quantities of water and occupying space, thus cushioning or lubricating other structures, is due to the large number of OH groups and negative charges on the molecules, which, by repulsion, keep the carbohydrate chains apart. Examples are hyaluronic acid, chondroitin sulfate, and heparin (Figure Table 13-5. Carbohydrates found in glycoproteins. Table 13-5. Carbohydrates found in glycoproteins.

What are Second Generation GM Crops

Genomics-based strategies for gene discovery, coupled with high-throughput transformation methods and miniaturised, automated analytical and functionality assays, have accelerated the identification of valuable genes. The discovered genes may change the compositions of carbohydrates or the functionality of proteins and radically modify the properties of crop plants. Therefore, the real potential of GM technology to help address some of the most serious concerns of world agriculture has only recently begun to be explored. Modified crops resulting from plant biotechnology have the potential of providing major health benefits to people throughout the world. Examples include enhancing the vitamin and mineral content of staple foods, eliminating common food allergens, developing higher protein quality and quantity in widely consumed crops. The trend for this second generation of GM plants therefore is the development of GM foods with enriched nutrients, with improved functionality, and...

Ketogenesis Is Regulated At Three Crucial Steps

Ketogenesis Pathway

(1) Ketosis does not occur in vivo unless there is an increase in the level of circulating free fatty acids that arise from lipolysis of triacylglycerol in adipose tissue. Free fatty acids are the precursors of ketone bodies in the liver. The liver, both in fed and in fasting conditions, extracts about 30 of the free fatty acids passing through it, so that at high concentrations the flux passing into the liver is substantial. Therefore, the factors regulating mobilization of free fatty acids from adipose tissue are important in controlling ketogenesis (Figures 22-9 and 25-8).

Modifying Intestinal Microbiota Composition Through Intake Of Probiotics

In the human GIT, variability exists in bacterial numbers and composition between the stomach, small intestine and colon. The total bacterial count in gastric contents is usually below 103 per gram contents with numbers in the small intestine ranging from about 104 per ml of contents to about 106-107 at the terminal ileum (79). In comparison to other regions of the GIT, the human large intestine is a complex, heavily populated and diverse microbial ecosystem. Bacterial numbers in the human large intestine are in the range of 10n-1012 for every gram of the gut contents (80). The colonic microbiota is capable of responding to anatomical and physicochemical variations that are present. The right or proximal colon is characterized by a relatively high substrate availability (due to dietary input), a pH of around 5.5-6.0 (from acids produced during microbial fermentation) and a more rapid transit than the distal region. The left or distal area of colon has a lower concentration of...

Dehydrogenases for large substrates

Our experience has been that most dehydrogenases prefer relatively small substrates (MW 150).22 In most cases, the natural substrates for dehydrogenases are unknown, but it is likely that many prefer carbohydrates or their derivatives.30 Since active sites are probably optimized for pentoses or hexoses, finding dehy-drogenases that accommodate larger synthetic intermediates becomes a challenge. The rapid screening approach described above could help this situation. If computational modeling allows active site size prediction for uncharacterized dehydrogenases, the best candidates could be identified in silico, then experimentally verified in short order. Alternatively, combining computer modeling with judicious mutagenesis and rapid mutant screening could allow variants with enlarged substrate-binding pockets to be created and characterized.

Thiamin Deficiency Affects the Nervous System Heart

Pyruvate dehydrogenase means that in deficiency there is impaired conversion of pyruvate to acetyl CoA. In subjects on a relatively high carbohydrate diet, this results in increased plasma concentrations of lactate and pyruvate, which may cause life-threatening lactic acidosis.

Carbohydrate Modification Reactions

Because carbohydrates are so frequently used as substrates in kinetic studies of enzymes and metabolic pathways, we refer the reader to the following topics in Ro-byt's excellent account1 of chemical reactions used to modify carbohydrates formation of carbohydrate esters, pp. 77-81 sulfonic acid esters, pp. 81-83 ethers methyl, p. 83 trityl, pp. 83-84 benzyl, pp. 84-85 trialkyl silyl, p. 85 acetals and ketals, pp. 85-92 modifications at C-1 reduction of aldehydes and ketones, pp. 92-93 reduction of thioacetals, p. 93 oxidation, pp. 93-94 chain elongation, pp. 94-98 chain length reduction, pp. 98-99 substitution at the reducing carbon atom, pp. 99-103 formation of gycosides, pp. 103-105 formation of glycosidic linkages between monosaccharide residues, 105-108 modifications at C-2, pp. 108-113 modifications at C-3, pp. 113-120 modifications at C-4, pp. 121-124 modifications at C-5, pp. 125-128 modifications at C-6 in hexopy-ranoses, pp. 128-134.

Symbiosis and modern biology

The recognition of symbiotic relationships has had a revolutionary impact on modern biological thought. The idea that mitochondria and chloroplasts are transformed by symbiotic bacteria provides a common thread to the biological world and raises hope of finding other symbiotic wonders among life's diversity. Plants and animals have acquired new metabolic capabilities through symbioses with bacteria and fungi. Mammalian herbivores and termites digest cellulose with the help of microbial symbionts. The luminescent bacteria contained in the specialized light organs of some fishes and squids produce marine bioluminescence. Diverse animal life around deep-sea vents is based on symbiosis with bacteria that oxidize hydrogen sulfide and chemosynthetically fix carbon dioxide into carbohydrates. Associations between fungi and algae have resulted in unique morphological structures called lichens. Early land plants formed associations with mycorrhizal fungi, which greatly facilitated their...

Robert K Murray MD PhD

Glycoproteins are proteins that contain oligosaccharide (glycan) chains covalently attached to their polypeptide backbones. They are one class of glycocon-jugate or complex carbohydrates equivalent terms used to denote molecules containing one or more carbohydrate chains covalently linked to protein (to form glycoproteins or proteoglycans) or lipid (to form glyco-lipids). (Proteoglycans are discussed in Chapter 48 and glycolipids in Chapter 14). Almost all the plasma proteins of humans except albumin are glycoproteins. Many proteins of cellular membranes (Chapter 41) contain substantial amounts of carbohydrate. A number of the blood group substances are glycoproteins, whereas others are glycosphingolipids. Certain hormones (eg, chorionic gonadotropin) are glycoproteins. A major problem in cancer is metastasis, the phenomenon whereby cancer cells leave their tissue of origin (eg, the breast), migrate through the bloodstream to some distant site in the body (eg, the brain), and grow...

Microbiota Of The Gastrointestinal Tract In Farm Animals

The gastrointestinal microbiota interact profoundly with their animal host, influencing its early development, quality of life, ageing and resistance to infectious diseases. One of the functions of the microbiota is to degrade dietary components such as fiber in order to provide short-chain fatty acids and other essential nutrients that are absorbed by the host. Animal hosts have incubation chambers such as the rumen (cattle, sheep, goat) or the caecum (horse, chicken) in which bacterial fermentation proceeds under optimal conditions. Those animals that have only small caeca, (pigs), have a microbiota which has adapted to use fast food such as simple carbohydrates and proteins that are consumed with the diet and available in the host's secretions such as saliva or mucus (3).

Complex Phenotypes Arise Out Of A Few Basic Processes

We haven't covered all biological systems in this book by any means. We've concentrated on particular phenomena that are important to understanding how complex organisms work and how they got that way. The principles and often even the specific genetic phenomena are, however, similar for systems that we have not mentioned. For example, digestion involves the breakdown, absorption, and so on of proteins, fats, sugars, and other carbohydrates, using gene products just like the other systems (e.g., proteases, binding factors). Kidney filtration rests on ion channels and similar structures. Many of these are pure chemical processes that is, they involve genes to the extent of synthesizing chemicals (e.g., HCl, pancreatic enzymes) and secreting them from cells but are mainly not informational in the sense of most systems and phenomena in which we have been interested here.

Photoreception In Plants

Diagram Cholorplast Figure

Plants build carbohydrates from light energy and raw materials from water and CO2. In the natural cycle of the biosphere, they obtain hydrogen from water and carbon and oxygen from the CO2 expelled into the atmosphere by animals. The carbon and O2 are taken into leaves through stomata, and water is taken up by roots and circulated up through the vasculature to the leaves, where the light energy is used to break down the raw materials into hydrogen, carbon, and oxygen, which are then recombined into carbohydrates. The plant subsequently uses these carbohydrates as energy, stores them, or builds them into more complex molecules such as oils or proteins. There are 200 to 300 pigment molecules bound to protein complexes in the pho-tosynthetic, or thylakoid, membrane of the chloroplast (Figure 14-7B), and they form an antenna system that absorbs light energy and transfers it in the form of excited electrons to a chlorophyll molecule that serves as a reaction center. The reaction center...

Relationship Of Cell Structure To The Concept Of A Tree Of Life

The Structure Family Life

Stromatolites are prokaryotic organisms that most closely resemble modern cyanobacteria (Schopf 2000), single-celled, photosynthetic organisms that contain a blue pigment in addition to chlorophyll and that live singly or in colonies. Their descendants or closely related organisms still thrive cyanobacteria are commonly found as the green scum on a stagnant pond. Interestingly, if indeed these earliest life forms were cyanobacteria, this would mean that photosynthesis had already evolved more than 3.5 billion years ago. Green plants use photosynthesis to synthesize carbohydrates from carbon dioxide and water, using light as the source of energy, thus suggesting that water and carbon dioxide were present very early in Earth's history (Schopf 1992,1994, 2000).

[2 Imaging Platforms for Measurement of Membrane Trafficking

Membrane traffic enables cells to distribute proteins, lipids, and carbohydrates between membrane compartments and is thus vital for many cellular processes such as cell growth, homeostasis, and differentiation. Genetic and biochemical approaches have been very efficiently applied in the past to identify and characterize individual molecular components involved in the regulation of membrane traffic in the secretory and endo-cytic pathways. Central to many of these studies has been the reconstitution of the particular transport step of interest in vitro using purified components. Although this has led to an enormous body of information on how membrane traffic is organized at the molecular level, such simplified in vitro systems are lacking important regulatory elements relating to the spatial organization that occurs in living cells. More recently, systematic approaches, such as organelle proteomics or yeast two hybrid screening, have attempted to identify structural and regulatory...

Adaptations in the digestive system

Digestive System Mammal

All carnivores, when fed a whole prey-based diet, consume proteins and fats from the muscle, vitamins from organs and gut contents, minerals from bones, and roughage from the hide, feathers, hooves, teeth, and gut contents. Felids are set apart from other, more omnivorous meat eaters because of their inability to effectively utilize carbohydrates as an energy source. They therefore depend on a higher concentration of fats and protein in their diet, as well as dietary sources of preformed vitamin A and D, arachadonic acid (an essential fatty acid), and taurine.

Blood Volume and Composition

In addition to red blood cells, which comprise more than 99 of the blood cells, the formed elements of the blood include white blood cells and blood platelets. Plasma is a complex mixture that includes water, amino acids, proteins, carbohydrates, lipids, vitamins, hormones, electrolytes, and cellular wastes.

Critical Thinking Questions

In Hunter syndrome, lack of an enzyme leads to build up of sticky carbohydrates in the liver, spleen, and heart. The individual is also deaf and has unusual facial features. Hunter syndrome is inherited as an X-linked recessive condition. Intellect is usually unimpaired and life span can be normal. A man who has mild Hunter syndrome has a child with a woman who is a carrier (heterozygote).

Cellular Adhesion Molecules

Blood Vessels

Of CAM called a selectin does this by coating the white blood cell and providing traction. The white blood cell slows to a roll and binds to carbohydrates on the inner capillary surface. Clotting blood, bacteria, and decaying tissue at the injury site release biochemicals (chemoat-tractants) that attract the white blood cell. Finally, a type of CAM called an integrin contacts an adhesion receptor protein protruding into the capillary space near the splinter and pushes up through the capillary cell membrane, grabbing the passing slowed white blood cell and directing it between the tilelike cells of the capillary wall. White blood cells collecting at an injury site produce inflammation and, with the dying bacteria, form pus. (The role of white blood cells in body defense is discussed further in chapter 16, pp. 661-666.)

Angleclosure Glaucoma

Glycerol is administered as a liquid in dosages of 1 to 1.5 g kg of body weight,3 either as a 100 solution mixed with an equal volume of iced juice or as a commercial preparation (Osmoglyn, 50 solution). Oral glycerol is rapidly absorbed, is distributed throughout the extracellular water, and penetrates the eye poorly. The drug is metabolized by the liver rather than excreted by the kidneys, producing less diuresis than do other hyperosmotic agents. Glycerol has an unpleasantly sweet taste and may cause vomiting. The caloric content is 4.32 cal g, which, combined with the osmotic diuretic effect and resultant dehydration, mandates special caution when used in diabetic patients, who may develop hyperglycemia and ketosis.4

Human Flora Associated Animals

Observed in mice that were fed with an amylose rich diet (Fig. 2). This suggests that diet, and specifically dietary ingredients such as certain carbohydrates, are important for the composition of the GI microbota and that previously nondetectable microbial groups may be stimulated to detectable levels. Consideration may be given to the possibility that the growth of microbal populations due to dietary intervention, may be at the expense of less competitive microbial groups. HFA rodents are useful in studies of the metabolic activity of the human microbiota. The effects of microbiota on the metabolism of lignans and isoflavones have been investigated in studies using germ-free and HFA rats (98). In similar studies, HFA rats have been used to assess the metabolism of dietary fats (99,100). The usefulness of HFA animals has also been illustrated in studies such as those conducted on the effect of complex carbohydrates on the human microbiota, including the effect of resistant starch...

Carbohydrate Cell Surface Cancer Antigens The Mskcc Experience

With the exception of MUC1 and KSA, all of the widely expressed antigens on these cancers were carbohydrates. Our results are consistent with those from other centers with one exception We did not find increased levels of GD2 or GD3 in SCLC. There is a striking similarity in expression of these 12 antigens among tumors of similar embryo-logic background (i.e., epithelial vs neuroectodermal). Epithelial cancers (breast, ovary,

The SHBsAg Protein and the Assembly of HDV Particles

Protein should be present on S-WHsAg and absent on the small DHBV envelope protein (S-DHBsAg). Compared to S-HBsAg or S-WHsAg, the S-DHBsAg polypeptide appears to lack the region corresponding to the antigenic loop between TMD2 and the carboxyl terminal hydrophobic domain (Fig. 3). When part of this domain (from residues 107 to 147) was experimentally deleted on S-HBsAg, it led to a drastic reduction in the capacity of the mutant for HDV maturation (O'Malley and Lazinski 2002). Interestingly, this deletion mutant was competent for the envelopment of the singly expressed L-HDAg protein, suggesting that the hindrance observed in RNP envelopment may rather reflect a lesser flexibility of the envelope, which could no longer accommodate an RNP, than a lack of binding. On one hand, S-DHBsAg cannot package the RNP and cannot interact with L-HDAg, and on the other hand, a S-HBsAg mutant that mimics S-DHBsAg in lacking the antigenic loop, is also deficient for packaging the RNP, while...

Simple sugars and lowermolecularweight oligomers

Sugar determinations are important in the food industry, in analysis of carbohydrates and their polymers, and in pharmaceutical analysis of glyco-proteins. A number of column types have been used in the separation of sugars, particularly amino columns and strong anion exchange columns. Amperometric detection is widely used, but post-column detection schemes, UV detection, and refractive index detection are also useful. Sugars are capable of being linked together at a number of locations on the ring, making the determination of linkage and branching one of the most challenging issues in analysis. In Figure 19 is shown a-d-glucose and the linkage points from which oligomers and polymers may be formed.

Nonneoplastic Conditions

White red patches the oral mucosa may become white due to accumulation of keratin or epithelial hyperplasia and may become red because of epithelial atrophy, increased vascularity or inflammation. Physical stimuli such as friction from teeth or dentures or through the use of tobacco can produce an irritational keratosis on any part of the oral mucosa, most often lining mucosa. Chevron parakeratosis and melanin incontinence point to tobacco-related lesions. Lichen planus lichenoid reaction occurs commonly on the lining mucosa and dorsum of tongue as white striae or papules against a red background. Erosive forms are characterised by ulceration. Some lesions are a consequence of systemic drug therapy or as a response to amalgam restorations in adjacent teeth. Geographic tongue is characterised by irregular areas of mucosal erosion affecting the dorsal surface. Central areas of atrophy are outlined by a narrow peripheral zone of white mucosa and may be accompanied by deep fissuring of...

Possibilities and Limitations of Rumen Simulation Methods

The duration of the fermentation in closed batch culture should be adjusted carefully according to the substrates and cell density to prevent the deprivation and inhibitory effects of accumulating metabolites. As a consequence in either case, the most fastidious bacteria and protozoa are at risk of being lost. A shorter incubation time should be used with substrates that are rapidly fermented. By using actual feed components and compositions, the risk of substrate deprivation during simulations is reduced. For example, Leedle and Hespell (54) have reported the selective effects of single or purified carbohydrates and nitrogen substrates on microbial population. The amount of feed should be not only adequate in relation to the microbial density in vitro, but also in relation to the calculated total digestive nutrient requirement of the host (44).

Structural Features And Energetics

The structural features of monovalent lectin-ligand complexes have been elucidated through X-ray crystallographic analysis 1,18-20 . These complexes have helped facilitate an understanding of the energetics of monovalent carbohydrate binding to proteins they have facilitated structure-based free energy calculations, as well as providing a basis for interpretation of titration microcalorimetry experiments 10,21 -23 . Although proteins can bind carbohydrates tightly, lectin binding sites are often solvent-exposed indentations rather than deep binding pockets. In these shallow binding sites, contacts are made with a limited portion of the carbohydrate ligand (Figs. 1 and 2). Monovalent interactions appear to rely on hydrogen bonding, metal chelation, water displacement and reorganization, hydrophobic contacts, and Coulombic interactions. We will use specific protein-lectin interactions to illustrate these energetic contributions. Coulombic interactions between carbohydrate binding...

Vertebrate Immune Responses

The system is activated via three pathways. The first is called the classical pathway, activated by antigen-antibody complexes and active in both innate and adaptive immunity. The second is the mannan-binding lectin pathway (MBLectin pathway), which responds to the binding of a serum protein called mannan-binding lectin to carbohydrates on bacteria or viruses that contain mannose, a type of sugar molecule. Finally, the alternative pathway is activated when the surface of a pathogen is bound by a previously activated complement component (Janeway 2001).

History and Uses of Plant Biotechnology

Undoubtedly however, classical breeding has dramatically increased the productivity of the plants we grow for food, fibre and other purposes. The so-called Green Revolution during the years 1950-1965 involved the simultaneous effects of breeding efforts and altered agricultural practices. New crop varieties and the availability of pesticides and fertilisers greatly increased the needed crop yields in developing countries. Mexico, for instance, was importing half of its wheat consumption in 1944. In 1956 the country was self-supporting, and by 1964 Mexico was exporting 0.5 million tons of wheat. Apart from crop yield, significant progress was made in improving the quality of plant products such as proteins, carbohydrates, fibre or oil content.

Structure And Function Of The Human Sult1a Subfamily

The substrate-binding region of the SULT1A subfamily will mainly be reviewed based on the recently solved SULT1A1 structure. Figure 10.6, a-c (see color photo insert following p. 210), shows that a deep hydrophobic pocket comprises the substrate-binding site for cytosolic SULTs, whereas the presumed substrate-binding site of the human membrane-bound NST1 (SULT domain of human N-deacetylasel N-SULT1), which is responsible for the sulfonation of large molecules such as carbohydrates, glucosaminylglycans, and proteins, has a large open cleft (Figure 10.6d see color photo insert following p. 210). However, as mentioned above, the resolved structure of SULT1A1 revealed an L-shaped substrate-binding pocket that is larger than that anticipated from the disordered SULT1A3 structure. The residues lining the substrate-binding pocket of SULT1A1 were found to be well ordered and predominantly hydrophobic (Phe81, 142, 24, 84, 76, 247, 255, Ile89, His149, Tyr169, Tyr240, Ile21, Ala146, 86, Met248,...

Ginseng And The Ageing Process

As people's lives become longer, particularly in the more civilised societies which have adequate medical and preventative services, ageing presents many problems. As we age we become less physically fit, we show obvious changes such as whitening or loss of hair, wrinkled skin which recovers more slowly from the pinch test, weakened hearing and vision, general slowing down of physical activities and we become more liable to suffer from various illnesses. Less obvious is the deterioration of the body organs prompting glandular disorders, reduction of hormone output leading to sexual impotency, gradual mental deterioration and breakdown of the immune system. Any life style, drug or medicine that can delay or slow this inevitable decline and improve the quality of life is therefore important. The ancient Chinese were convinced that ginseng was the tonic that fulfilled this role. After all, it is an adaptogen coping with stress, it is a metabolism regulator for proteins, carbohydrates and...

Diagnosis of gestational diabetes

For the three-hour GTT, women are advised to consume an unrestricted diet containing at least 150 grams of carbohydrates daily three days prior to testing. They are asked to fast for 10-14 hours prior to testing. All tests are performed in the morning. Blood is drawn fasting and at 1, 2, and 3 hours postingestion of a 100-gram glucose-containing solution. If any two (out of 4) or more results are abnormal, then they are diagnosed as having gestational diabetes.

Syntheses of Suitably Functionalized Sialosides

To this end, suitably functionalized V-acetylneuraminic acid derivatives were required. A convergent approach in which various sialoside haptens and other carbohydrates of interest could be attached to multivalent scaffolds at a late stage was chosen. This strategy offers the advantage of permitting further optimization of binding interactions where appropriate.

Introduction Of Head Circumference

The completely developed skin can be considered to have three layers the epidermis, the dermis, and the subcutis, which is loose subcutaneous tissue. The surface of the epidermis is keratinized and covers an area of approximately 1.5 to 2 m2, weighing 0.5 kg in an adult. There is variation in epidermal thickness, depending on the body area. The skin is thinner, for example, around the eyes and lips, and is thicker in the palmar and plantar areas. On average, the skin is 0.1 cm thick. The dermis is separated from the epidermis by a basal membrane. The dermis consists of collagen, elastin, and reticular fibers, as well as a variety of cell types and a matrix with many complex carbohydrates. The subcutis or subcutaneous tissue

Nutrition And Esophageal Adenocarcinoma

The increasing incidence of esophageal adenocarcinoma over the course of the past 30 years has provoked scientific and epidemiologic interest. Most relevant, nutrition-based research to date consists of case-controlled studies. Nonetheless, certain dietary associations with the disease have emerged (Fig. 3). Obesity and a high fat diet have been seen to increase the risk of esopha-geal cancer, whereas several nutrients appear to reduce its incidence. These are discussed individually. High Fat Diet

Aldehyde Groups And The Schiff Reagent

The periodic acid-Schiff (PAS) reaction stains carbohydrates and carbohydrate-rich macromolecules. It is used to demonstrate glycogen in cells, mucus in various cells and tissues, the basement membrane that underlies epithelia, and reticular fibers in connective tissue. The Feulgen reac Hexose rings of carbohydrates contain adjacent carbons, each of which bears a hydroxyl ( OH) group. The PAS staining of basement membrane (Fig. 1.2) and reticular fibers is based on the content or association of proteoglycans (complex carbohydrates associated with a protein core). PAS staining is an alternative to silver impregnation methods, which are also based on reaction with the sugar molecules in the proteoglycans.

Using Sialyltransferases For The Synthesis Of Sialosides

Enzyme-mediated glycosylations are powerful methods for the synthesis of complex carbohydrates, including those that contain sialic acid 30,31 . In mammalian systems, Leloir pathway glycosyltransferases are responsible for the biosynthesis of most glycoconjugates 32 . Sialyltransferases are a subset of the glycosyltransferases that transfer the NeuAc component of acid (88, CMP-NeuAc) to acceptor hydroxyl groups with inversion of configuration at the anomeric center (Scheme 28) 30,31 . Transferase-mediated sialylations are not burdened by some of the pitfalls of chemical glycosylations, such as un-

Lowvalent Glycoclusters for Directed Multivalency

Low-valent glycoclusters have been important for defining the structural features required for high-affinity binding to multivalent receptors. As discussed above, rigid miniclusters are particularly affine ligands - if the carbohydrates are properly oriented, enabling unstrained multidentate binding. Rigid miniclusters are, in principle, moreover, able to differentiate between various multivalent lectins with the same carbohydrate specificity but varying orientation of their binding sites. If, however, the 3D structure of the targeted lectin is unknown, large numbers of potential ligands have to be synthesized and screened to identify the required presentation of the sugar residues. Fig. 2.7.3. Cluster glycosides synthesized by Lee et al. and their binding to ASGPR on isolated rabbit hepatocytes 7 . Carbohydrate residues involved in multivalent binding are highlighted in gray. The residual carbohydrates are assumed to function as a scaffold. Fig. 2.7.3. Cluster glycosides synthesized...

Diagnostic Characteristics

And sleep maintenance insomnia, and the consumption of high carbohydrate snacks during many of the awakenings. It was described recently in detail by Birketvedt et al. (7). Diagnostic criteria for this syndrome are evolving, and it is not included as a diagnostic category in the DSM-IV. Proposed clinical criteria are shown in Table 1.

Nonpsychotic Disorders

Because alcohol is rich in carbohydrates but low in proteins and vitamins, long-term users can develop cirrhosis of the liver due to protein deficiency or Korsakoff's syndrome due to vitamin B deficiency. The symptoms of Korsakoff's syndrome, a chronic brain disorder occurring most often in chronic alcoholics in their fifties and sixties, include disorientation, impulsiveness, memory loss, confabulation,1 and inflammation of the peripheral nerves of the body.

Syntheses And Structural Characterization Of Amidolinked Oligomers With Stable Secondary Structure

Non-Carbohydrate-Based Materials Although this chapter is focused on carbohydrate-based compounds, it is important to briefly describe the pioneering work of Gellman and Seebach directed to the syntheses of amido-linked oligomers derived from - and y-amino acids that are not based on carbohydrates. These researchers and others 55 have engineered systems that adopt stable helical, sheet, and turn conformations in solution. Surprisingly, in many cases as few as four residues is sufficient to stabilize the conformation. This completely contrasts with oligomers derived from a-amino acids which typically require many more residues before conformational stability is established 56 .

Specificity in Multivalent Recognition Concanavalin A Discriminates Between Related Multidentate Ligands

The specificity of ligand binding for a multivalent protein-carbohydrate interaction was explored by using ConA. ConA binds both glucose and mannose residues, but it binds monovalent C-mannoside 9 with a slightly (0.2 kcal mol) more favorable free energy than the corresponding C-glucoside 8 (Fig. 12) 54 . Whether the small difference observed in the monovalent binding event would be manifested with the corresponding multivalent ligands has been explored. By examining the ability of glucose- and mannose-substituted polymers to inhibit ConA-mediated agglutination, the inhibitory potencies of mannose-modified polymer 11 could be compared with the corresponding glucose counterpart 10 in a hemagglutinaton assay (Fig. 12). Not surprisingly, no difference in potency was detected between the glucose and mannose monovalent C-glycosides 8 and 9. The activity difference between the glucose- and mannose-substituted polymers, however, is greater than 100-fold 31 . Consequently, multivalent...

Coupling Via Glycosyl Oxophosphonium Intermediates

Glycosyl Amino Acids

Mukaiyama and coworkers have developed an alternate method for the generation of glycosyl oxophosphonium intermediates. This method is based on Hen-drickson's earlier work concerning the development of phosphonium anhydride dehydrating reagents, prepared by the reaction of triphenylphosphine oxide (2 equiv) and triflic anhydride (1 equiv) 38 . With the reagent combination of tributyl phos-phine oxide (2 equiv) and triflic anhydride (1 equiv), Mukaiyama reported that the resulting diphosphonium salt 41 (Scheme 10) 39 efficiently converted the hemiacetal functionality of 1-hydroxy carbohydrates to the anomeric oxophosphonium species 42, an effective glycosylating agent. In the presence of i-Pr2NEt as an acid scavenger, glycosylation of a number of simple alcohols, O-TMS-protected alcohol acceptors, and even azide acceptors, can be effected with 2,3,5-tri-O-benzyl-d-fura-nose to afford the product glycosides (e.g., 43-45).

Naturally Occurring Pyranosyl Sugar Amino Acids

Sugar amino acids are carbohydrates containing both amine and carboxylic acid functionalities in place of hydroxyls and are structurally distinct from glycopeptides. Naturally occurring sugar amino acids come in several types, consisting of both amino furanosiduronic and pyranosiduronic acids. This chapter includes the latter class of compounds, often referred to as amino hexuronic acids. Hexuronic acids are six-carbon monosaccharides containing both an aldehyde and a chain-terminating carboxylic acid. The amino hexuronic acids have amine functionalities in place of hydroxyl groups normally found in sugars.

Low Molecular Weight Trimeric Galactose Displays Can Be Potent Ligands for the Hepatic Lectin on the Cell Surface

Multivalent displays of galactose and -acetylgalactosamine epitopes have been synthesized to identify the features important for glycoconjugate recognition and en-docytosis by the hepatic lectin 117,118 . Initial studies, performed with galactose-substituted neoglycoproteins and polyacrylamide gels, demonstrated that the receptor binds more efficiently to multivalent ligands 119 . Since many natural saccharides contain branched or multiantennary structures, several groups postulated that high-affinity recognition of carbohydrates in biological systems requires the presentation of clustered saccharide residues 108,118 . To test this idea and to elucidate structure-function relationships, Lee's group and others have synthesized a number of nonnatural low molecular weight multivalent compounds 97,108,109,120 . The compounds were evaluated for their ability to inhibit the binding to hepatocytes of radiolabeled asiolomucoid, a ligand for the hepatic lectin. A synthetic trivalent compound,...

Analyzing Glycosylation Changes

Numerous factors exist which lead to differential glycosylation of glycopro-teins. Viral envelope proteins expressed by different viral strains may be differentially glycosylated, as demonstrated for the Ebola virus by Lin et al. (10). Variability in the sequence of viral envelope proteins among different isolates may directly lead to loss of oligosaccharide acceptor sites or may alter protein conformation, thereby preventing access of the cellular glycosylation machinery to potential glycosylation sites (2). Secondly, changes in culture conditions or producer-cell type may result in the expression of a number of different gly-coforms, because different cell types may differ in the repertoire of glycosyl-transferases and glycosidases expressed, and in the time taken for proteins to transit the secretory pathway. For instance, the glycosylation of HIV gp120 varies significantly between CD4+ T cells and macrophages, the two cellular targets of HIV infection in vivo, with Env produced in...

PTPs and Human Disease

Recent progress in establishing links between PTPs and human diseases, together with developments in understanding the function of several of these enzymes, has raised awareness of the PTPs in the pharmaceutical industry. The appreciation that PTPs have the ability to display specificity for substrates in vivo and, therefore, to exert effects that would be restricted to specific signaling pathways suggests that PTP-directed drugs would induce defined, rather than global, changes in cellular tyrosine phosphorylation. A spectacular example of the potential importance of PTPs in the development of novel therapeutic strategies was provided by the phenotype of the PTP1B knockout mouse. The mice show no obvious deleterious effects however, they display enhanced sensitivity to insulin and a resistance to obesity induced by a high-fat diet, which is accompanied by increased basal metabolic rate and total energy expenditure 59,80 . These effects have been defined in terms of a regulatory...

Carbohydrate Structure and Diversity

Most of the current evidence for the biological roles of complex carbohydrates comes from systems where they act as ligands for membrane-bound receptors that are lectins. Typically, these receptors have one or more extracellular CRDs, a single transmembrane-spanning region, and a relatively short cytosolic tail. In most cases, they are probably activated by receptor cross-linking mechanisms. Carbohydrates and Lectins in the Nucleocytosolic Compartment Galectins are also cytosolic and nuclear proteins, but they are not known to bind carbohydrates in these compartments however, galectins 1 and 3 have been implicated in pre-mRNA splicing, a process inhibited by oligosaccharide binding 69 . The galectins are also secreted from the cytoplasm (by non-classical pathways), and it is at the cell surface that they perform the carbohydrate-mediated processes discussed previously.

Peripheral Energy Metabolism 6321 p3Adrenergic Receptor

To demonstrate the requirement for p-adrenergic receptors in diet-induced thermogenesis, mice lacking the p3-adrenergic receptor were generated and shown to have modestly increased fat stores.164 Mice lacking p-adrenergic receptors 1, 2, and 3 were also produced.165 They were mildly obese, showed lowered metabolic rates, and were cold intolerant. On a high-fat diet, they became massively obese compared with wild-type controls.

Protein misfolding and its consequences for disease

Amyloidois Images

The deposition of proteins in the form of amyloid fibrils and plaques (Selkoe, 2003). Such deposits can form in the brain, in vital organs such as the liver and spleen, or in skeletal tissue, depending on the disease involved. In the case of neurodegen-erative diseases, the quantity of such aggregates can be almost undetectable in some cases, whilst in systemic diseases kilograms of protein can be found in such deposits. Each amyloid disease involves primarily the aggregation of a specific peptide or protein although a range of other components including other proteins and carbohydrates is also incorporated into the deposits when they form in vivo. The characteristics of the soluble forms of the twenty or so proteins involved in the well-defined amyloidoses are very varied -they range from intact globular proteins to largely unstructured peptide molecules - but the aggregated forms have many common characteristics in common (Sunde and Blake, 1997). Thus, amyloid deposits all show...

Chemical Modification by Pegylation

Pegylation of proteins has been used successfully to increase the serum half-life of proteins (136). Pegylation involves chemical attachment of the polymer polyethylene glycol (Peg), to reactive regions of proteins or carbohydrates. Pegylated molecules have an increased hydrodynamic size because they create a water shell around the molecule. The increased hydrodynamic size can result in reduced clearance and thus allow the vivo activity of the protein to be conferred for a longer period of time.

Future of Transgenic Mouse Approaches Need for Inducible Expression

Many eukaryotic promoters are under natural inducible control, providing a simple means for controlling the extent and duration of expression. For example, in the absence of heavy metals, the MT promoter has low activity. Treatment with cadmium or zinc, however, increases promoter activity several fold. The effectiveness of this induction scheme was demonstrated in transgenic mice harboring a mutated sheep MT promoter linked to an ovine GH-cod-ing sequence. When maintained on water supplemented with zinc, these mice secreted excessive levels of GH and displayed a giant phenotype (Shanahan et al., 1989). Mice overexpressing GH have also been made with a transgene that utilizes the PEPCK promoter (McGrane et al., 1988). Transcription of the chimeric gene occurred after birth in the kidney, liver, and adipose tissue. This promoter is regulated by composition of the diet a diet high in carbohydrates reduces expression whereas a diet high in protein and low in carbohydrate stimulates...

And Kenneth A Foon MD

Active specific immunotherapy (ASI) is an attractive approach to cancer therapy, especially in an adjuvant setting. ASI is intended to boost or induce a host antitumor response, in contrast to passive immunotherapy, where large doses of preformed antitumor antibodies, or T cells with predetermined specificity, are infused. In classical ASI, patients are vaccinated with purified tumor-specific or tumor-associated antigens (TAAs). This approach has a number of major limitations. The tumor antigens are usually weakly immunogenic due to the induction of tolerance. This tolerance can be broken by presentation of the critical epitope in a different molecular environment (1). Secondly, it is difficult to obtain the purified antigen in sufficient quantities for vaccination. Although this limitation can be overcome by the synthesis of well-defined antigens by use of recombinant DNA technology, the recombinant molecule may not resemble the native structure of the protein. Moreover, mass...

Exercise Plus Caloric Restriction for Inducing Weight Loss

These modest benefits of exercise may be masked in studies of VLCDs in which the marked restriction of calories and carbohydrates results in large losses not only of fat but also of water and lean body mass (49). Wadden and colleagues (51), for example, examined weight loss of patients who consumed a 925 kcal d (3870 kJ) diet for 16 of the first 24 weeks and were randomly assigned to one of four conditions no exercise aerobic exercise strength training or aerobic plus strength training. Participants in the three exercise conditions attended three supervised sessions a week. At the end of 24 weeks, participants in the four conditions lost 18.6 , 16.4 , 18.1 , and 19.9 of initial weight, respectively. Thus, supervised exercise training appeared to have no effect on weight loss in the short term. Donnelly and colleagues (52) reached the same conclusions with a VLCD that provided 520 kcal d (2176 kJ), as did Hammer and colleagues (53) with a diet providing 800 kcal d (3350 kJ).

Biological Roles of Carbohydrate Recognition

Carbohydrates, in the form of oligosaccharides or glyco-conjugates, are found on the cell surfaces and extracellular proteins of virtually all living organisms. Although roles for carbohydrates in endogenous physiological interactions had long been suspected, it was not until the 1970s, with the discovery of the hepatic asialoglycoprotein receptor and Man-6-phosphate-mediated intracellular protein targeting, that firm evidence for such roles began to emerge. Since then, a number of animal lectin families have been identified 1,2 and their functions, in processes ranging from protein folding and quality control to leukocyte homing, have been the subject of considerable study. of roles for endogenous carbohydrate recognition in the development and functioning of the immune and nervous systems 3-5 . In addition, mutations affecting the elaboration of complex carbohydrates are now known to be the basis for a growing number of human diseases collectively known as the congenital disorders...

Select a Low Fat Low Energy Dense Diet

The role of a high-fat diet in inducing weight gain was highlighted by the WHO Consultation on Obesity (9) and gained general acceptance as an appropriate strategy for the prevention of obesity until questioned by some authors who expressed doubts about the efficacy and safety of this approach (48-50). Their skepticism was based on the association of increasing levels of obesity with decreasing proportion of dietary energy from fat in the U.S. national diet, a belief that high-carbohydrate diets resulted in increased CHD risk and the variable and inconsistent outcome of trials of low-fat diets. However, a review of U.S. dietary patterns over the period 1970-1994 by the U.S. Department of Agriculture (51) revealed that, while there was a de- -a crease in the percentage of energy from fat (from 42 to 38 ), the absolute amount of fat in grams available for consumption actually increased by 3 . This apparent paradox is possible because over the same time period the energy available per...

Analysis of the Glycosylation Status of the GSTTagged Proteins

As discussed previously, both mammalian and insect cells have different glycosylation pathways. The two systems process glycoproteins into a common intermediate, the N-glycan precursor, after which the glycosylation processes differ. In mammalian cells, these precursors are elongated to produce complex products containing terminal carbohydrates (e.g. galactose and sialic acid). The same precursors are not elongated in insect cells but produced paucimannose structures (Man3GlcNAc2Fuc). However, the same procedures can be used to analyse the glycosylation properties of recombinant proteins produced in both cell lines. The protein of interest is digested with two common endoglycosid-ases peptide N-glycosidase F (PNGase F) and Endoglycosidase H (EndoH). PNGase F is able to remove the entire carbohydrate moiety from proteins modified by N-linked glycoslyation, and EndoH specifically removes high mannose chains. The electrophoretic migration pattern for the digested and undigested

The Prebiotic Strategy To Modifying The Intestinal Microbiota

While the probiotic strategy aims to supplement the intestinal microbiota via the ingestion of live bacteria, the prebiotic strategy aims to stimulate the proliferation and or activity of beneficial microbial populations already resident in the intestine. The characteristics shared by all successful prebiotics is that they remain largely undigested during passage through the stomach and small intestine and selectively stimulate only beneficial populations of bacteria in the colon. That is not to say that prebiotics cannot be theoretically designed to target bacteria within the stomach and small intestine, but rather those currently developed tend to target bifidobacteria, which predominantly reside in the colon. Importantly, prebiotics should not stimulate the proliferation or pathogenicity of potentially deleterious micro-organisms within the intestinal microbiota. To date, most prebiotics have been non-digestible carbohydrates, particularly oligosaccharides. Since the prebiotics...

Mechanisms Of The Bifidogenic Effect

The mechanism(s) by which prebiotics promote the relatively specific proliferation of bifidobacteria remain speculative. It is probably due to the efficient utilization of these carbohydrates as carbon and energy sources by bifidobacteria relative to other intestinal bacteria, and their tolerance to the SCFA and acidification of the microenvironment resulting from fermentation. Additionally, many bifidobacteria adhere to large granular substrates such as resistant starch and these may provide a site for colonization as well as a substrate (13,169). The ability of bifidobacteria to use a wide variety of oligosaccharides and other complex carbohydrates reflects their evolution in the hind-gut of humans and animals where the ability to metabolize a diverse range of food and host-derived complex carbohydrates and glycoproteins provides a competitive advantage. Analysis of the Bif. longum genome has revealed a large number of proteins specialized for the catabolism of carbohydrates (170).

Design and Synthesis of a Library of Cyclic Neoglycopeptides

As scaffolds for the multivalent presentation of carbohydrate ligands we chose cyclic peptides of general type 9 (Figure 2.7.6) 15 . At the combinatorially varied positions indicated by gray circles, d- and L-amino acids without side-chain functionality and d- and L-diamino acids such as lysine, diaminobutyric acid, or dia-minopropionic acid are incorporated. The latter represent the points of attachment of the carbohydrates. This library design enables generation of spatial diversity in two dimensions. Positional diversity generates different carbohydrate patterns displayed on the scaffolds. Varying the stereochemistry of the amino acids increases spatial diversity by generating different backbone folds 18 . For attachment of the carbohydrates a new urethane-type linker based on the Aloc protecting group has been developed (Scheme 2.7.1) 15, 19 (for other linkers used in solid-phase synthesis see Chapter 6.1). In contrast with glycosylation reactions employing solid phase-bound...

Some General Types Of Genes

The Central Dogma of biology, that genes code for protein, led to the general notion that genes specify individual structural proteins and enzymes that control basic physiology. The idea (not always explicitly stated) was that an organism is built up of separate identifiable functions and that one gene coded for one function. We know this is an overstatement, and one that can be quite misleading, but it is a view that has persistent effects on biology and biological research. The traditional kinds of genes, perhaps those most easily understood, code for extracellular structural proteins like collagen, intracellular structural proteins like actins and spectrins, carrier molecules like albumin or hemoglobin, or enzymes that trigger reactions like insulin or hormones, as well as for catalysts of basic energy storage and release or catalysts of reactions in the production and manipulation of basic biomolecules such as nucleic acids, amino acids, carbohydrates such as sugars and starches,...

Relation Between the Anticoagulant Activity of 1 3Glucan Sulfates and Their Cross Reaction with HITAssociated Antibodies

To establish the structural requirements for the anticoagulant activity of sulfated carbohydrates, as well as for the development of platelet-activating immune complexes in the presence of HIT antibodies, we synthesized structurally well-defined sulfated polysaccharides (Greinacher et al., 1995). The resulting (-1,3-glucan sulfates (GluS) varied in their DS, MW, sulfation pattern, and chemically introduced glycosidic side chains (Fig. 4). Although these compounds differ structurally from heparin, they exhibit structure-dependent anticoagulant as well as antithrombotic activities (Alban et al., 1995 Franz and Alban, 1995). They also induce platelet activation in the presence of HIT antibodies (Greinacher et al., 1995). Therefore, neither uronic acids, amino groups, nor the a-1,4- or (-1, 4-glycosidic linkages found in heparin are essential for these biological properties.

Making More of Life The Many Aspects of Reproduction

Reproduction is so fundamental to life that it is one of the characteristics by which we define life. As well as the generation of new life in the short term, in the long term, reproduction provides an opportunity for heritable change of various kinds, and hence for evolution. A key view of 20th century biology was that life is basically a nucleic acid information phenomenon, in the dual senses that biological information flows from DNA to RNA to protein (the Central Dogma), but not the other way, both in an individual and across generations. Thus an important primary form of reproduction, replication, is molecular copying, of RNA for individual genes and of DNA for chromosomes. Replication of other molecules of life, such as amino acids, steroids, lipids, carbohydrates, and nucleic acid components themselves and reproduction of organisms follow as a result. We've seen in earlier chapters that this view can be tempered by other ways in which interited change can come about, but they...

Translational and Posttranslational Control

Many eukaryotic proteins are extensively modified after translation by the selective cleavage and trimming of amino acids from the ends, by acetylation, or by the addition of phosphates, carboxyl groups, methyl groups, and carbohydrates to the protein). These modifications affect the transport, function, and activity of the proteins and have the capacity to affect gene expression.

The Posttranslational Modifications of Proteins

After translation, proteins in both prokaryotic and eukaryotic cells may undergo alterations termed posttranslational modifications. A number of different types of modifications are possible. As mentioned earlier, the formyl group or the entire methionine residue may be removed from the amino end of a protein. Some proteins are synthesized as larger precursor proteins and must be cleaved and trimmed by enzymes before the proteins can become functional. For others, the attachment of carbohydrates may be required for activation. The functions of many proteins depend critically on the proper folding of the polypeptide chain some pro-

Insights from rodent models

Early loss-of-function studies focused on molecules previously identified as potentially important modifiers of lipid handling. From these studies, apoE (Plump et al., 1992 Zhang et al., 1992) and the LDL receptor (Ishibashi et al., 1993) were confirmed as important modifiers of cholesterol levels. Mice lacking either apoE or the LDL receptor develop significant atherosclerotic lesions when fed a high fat diet. This observation paved the way for a deluge of studies looking at genetic influences on atherosclerosis lesion size in apoE and LDL receptor knockout mice (Glass and Witztum, 2001). Consequently, a solid body of new information has emerged on the mechanisms regulating plasma lipoprotein levels and controlling the initial stages of atherogenesis. The obvious advantage of studying the effect of a gene in mice predisposed to developing atherosclerosis is that anti-atherogenic effects of a gene may be more readily detected (Table 24.3).

Familial hypercholesterolemia and statins

In fact, mortality prior to the beginning of the twentieth century did not differ significantly from standard mortality rates and most individuals with the mutation had a normal life span. It was only during the twentieth century that mortality rates of carriers increased dramatically over the standard rate. The increase in mortality in the twentieth century is likely to have been caused by environmental factors such as smoking and high fat diet working in conjunction with the LDL receptor mutation.

Fruit Color and Nutritional Value

Lycopene imparts red fruit color and also acts as a dietary antioxidant. In addition to these well-known vitamins and antioxidants, other compounds in tomato fruit with antioxidant properties include chlorogenic acid, rutin, plastoquinones, tocopherol, and xantho-phylls (Beecher 1998 Leonardi etal. 2000). Tomatoes also contribute carbohydrates, fiber, flavor compounds, minerals, protein, fats and glycoalkaloids to the diet (Davies and Hobson 1981 Gundersen et al. 2001). Whereas nutrition studies have often focused on a single dietary phytonutrient, research clearly indicates that there are many bioactive compounds in food products and that it may be the combination of compounds that confer the beneficial health effects described (Laquatra et al. 2005).

Presumptive Diagnostic Tests

Once organisms are detected on or in growth media, various techniques are used to determine the genus and species of the organism. For bacteria, the differential growth on select media, metabolism of various carbohydrates and other chemicals, and the presence of selected enzymes are often used for identification. Special stains that incorporate florescent dyes coupled with antibodies to selected organisms are used for identification of bacteria and viruses.

Significant Interactions

Antibiotic administration blocks metabolism of isoflavones to equol through inhibition of the intestinal microflora, whereas a high carbohydrate milieu increases intestinal fermentation and results in more extensive bio-transformation of physto-oestrogens (Setchell & Cassidy 1999).

Theory The Nature of Theory Building

Analyze theory-building how we will, we all must start in the middle. Our conceptual firsts are middle-sized, middle-distanced objects, and our introduction to them and to everything comes midway in the cultural evolution of the race. In assimilating this cultural fare we are little more aware of a distinction between report and invention, substance and style, cues and conceptualization, than we are of a distinction between the proteins and the carbohydrates of our material intake. Retrospectively we may distinguish the components of theory-building, as we distinguish the proteins and carbohydrates while subsisting on them. (Quine, 1960, pp. 4-6)

Recombinant Protein Expression in Plants to Obtain New Products

Transgenic plants are being used to develop novel products, such as modified oils, fibers, starches, and other carbohydrates, proteins with high contents of certain amino acids, enzymes, and other proteins of medical importance as well as antibodies, antigens, and even plastics.

The Possibility of Continuously Measuring Energy Metabolism

The small body size of insects offers the opportunity of continuously monitoring the total energy metabolism of a whole population over their total life span. This results in a ''metabolic picture.'' One can then test the influence of different treatments (e.g., temperature, light program, drugs, mating, virginity) on the energy consumption. We performed such measurements with Phormia using an infrared CO2 monitoring system (URAS). Due to the restriction on carbohydrates as energy-providing substrate, the CO2 output equals the O2 input and therefore gives a true picture of energy metabolism. Thirty-five flies were placed in a respiration chamber and fed in the usual manner with sugar and water. The relatively big volume of the chamber allows unrestricted flying and walking activity. Figure 21.4 shows an example of such a measurement.

Energy metabolism and ectothermy

Energy is used by organisms to maintain living processes, power locomotion and other activities, and fuel the synthesis of tissue in growth and reproduction. All vertebrates derive their usable energy from the oxidation of carbohydrates, lipids, and proteins in the food they eat. Reptiles do not expend large amounts of energy to maintain high levels of body temperature as do birds and mammals, which are en-dothermic. The latter maintain high body temperature with internal heat production coupled with insulation fur or feathers that minimizes losses of heat to the environment. Reptiles have lower rates of heat production and are not well insulated from thermal exchanges with the environment. They are ectothermic, meaning they depend on external sources of heat in the environment for maintenance of body temperature.

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