scholarly journals Targeted Degradation of Proteins — The Ubiquitin System

2021 ◽  
Vol 9 ◽  
Author(s):  
Aaron Ciechanover
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Chemical Composition ◽  
Nobel Prize ◽  
Building Blocks ◽  
Spoken Language ◽  
The Body ◽  
Cancer Center ◽  
Ubiquitin System ◽  
Specific Order

Proteins are the engines of all forms of life, for humans and for all the plant and animal kingdoms. Proteins are used both to build organs (such as bones, muscles, and skin) and to perform bodily functions. These functions range from digestion (processing food and converting it into energy), to enabling movement and sensation (sight and hearing), to protecting the body from foreign invaders with our antibodies, which are also proteins. What are proteins? They can be compared to words in a language that contains letters. In the Hebrew alphabet, there are 26 letters out of which countless words can be composed. But when we write, we use just a fraction of these infinite options, with the average number of letters in a word ranging between 3 and 8. The biological “protein alphabet” is comprised of 20 “letters” called amino acids, which are the building blocks of the proteins that make up the body. Proteins are chains of amino acid, linked together in a specific order governed by the DNA. Unlike the words of a spoken language, the average protein consists of hundreds of amino acids. The extensive length of proteins and the chemical composition of the amino acids make proteins sensitive to many factors, such as high temperatures, radiation, and chemicals. All these factors damage proteins and alter their fragile structures, negatively affecting how they function. When proteins are damaged or when they finish performing their functions and are no longer needed, the body breaks them down. With my doctoral adviser, Prof. Avram Hershko, and our research collaborator, Prof. Irwin Rose from the Fox Chase Cancer Center in Philadelphia, we discovered the mechanism responsible for targeted degradation of proteins in cells. This degradation can recognize damaged proteins or proteins that are not needed anymore, while leaving intact the “healthy,” functional ones. This mechanism is called the ubiquitin system after its principal protein, ubiquitin, which was the first protein we discovered in the system. Ubiquitin’s role is to tag undesirable proteins so that the cell’s “grinder” can recognize them and break them down, enabling the cell to function normally. In this article, we will explain the story of proteins and the ubiquitin system that we discovered in a study that earned us, among other prizes, the Nobel Prize in Chemistry in 2004.

scholarly journals Antifreeze glycopeptide diastereomers

2012 ◽  
Vol 8 ◽  
pp. 1657-1667 ◽  
Author(s):  
Lilly Nagel ◽  
Carsten Budke ◽  
Axel Dreyer ◽  
Thomas Koop ◽  
Norbert Sewald
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Antarctic Fish ◽  
Building Blocks ◽  
The Body ◽  
Ice Recrystallization ◽  
Harsh Conditions ◽  
Antifreeze Activity

Antifreeze glycopeptides (AFGPs) are a special class of biological antifreeze agents, which possess the property to inhibit ice growth in the body fluids of arctic and antarctic fish and, thus, enable life under these harsh conditions. AFGPs are composed of 4–55 tripeptide units -Ala-Ala-Thr- glycosylated at the threonine side chains. Despite the structural homology among all the fish species, divergence regarding the composition of the amino acids occurs in peptides from natural sources. Although AFGPs were discovered in the early 1960s, the adsorption mechanism of these macromolecules to the surface of the ice crystals has not yet been fully elucidated. Two AFGP diastereomers containing different amino acid configurations were synthesized to study the influence of amino acid stereochemistry on conformation and antifreeze activity. For this purpose, peptides containing monosaccharide-substituted allo-L- and D-threonine building blocks were assembled by solid-phase peptide synthesis (SPPS). The retro-inverso AFGP analogue contained all amino acids in D-configuration, while the allo-L-diastereomer was composed of L-amino acids, like native AFGPs, with replacement of L-threonine by its allo-L-diastereomer. Both glycopeptides were analyzed regarding their conformational properties, by circular dichroism (CD), and their ability to inhibit ice recrystallization in microphysical experiments.

scholarly journals 45 Opportunity with functional role of supplemental amino acids

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 24-24
Author(s):  
Yanbin Shen ◽  
Sung Woo Kim
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Social Stress ◽  
Functional Role ◽  
Building Blocks ◽  
Animal Production ◽  
The Body ◽  
Technological Advancement ◽  
Crystalline Amino Acids

Abstract The technological advancement in production of crystalline amino acids has driven the cost of crystalline amino acids down significantly and facilitated the wide use of crystalline amino acids in food animal production. The primary reason of use of crystalline amino acids in am animal’s diet is to provide dietary essential nutrients for protein synthesis and to balance the diet and reduce dietary cost. Extensive researches with amino acids have greatly enabled such use. As a result, most swine diets today are formulated with 3 or 4 supplemental amino acids. However, the economical return on including beyond 4 supplemental amino acids becomes low and thus discourages the use of more than 4 supplemental amino acids for dietary saving purpose. The use of the functional role of amino acids might bear the new opportunity for amino acids. Tryptophan has unique physiological functions involving synthesize serotonin in the body. Increasing tryptophan intake is shown to elevate serotonin synthesis in the brain of pigs and reduce stress and improve performance of pigs under social stress. Research shows that methionine is used as a precursor of glutathione to protect intestinal mucosa from oxidative damages during weaning stress. Arginine, glutamine, and glutamate are shown to have functions in cell proliferation, potentially improving intestinal and immune function of nursery pigs and preventing loss of lean body mass in the sow. Leucine is a ketogenic amino acid. The carbon skeleton of leucine is converted to acetylCoA, which could be used for fatty acid synthesis in muscle tissue. Research showed that intramuscular fat was increased by feeding high dietary leucine levels. Overall, the different functions of individual AA beyond their roles as the building blocks for proteins give additional opportunities of amino acid application in animal production.

Amino Acids Profiling in Fruit Juices by High Performance Liquid Chromatography: A Review

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2756-2767
Author(s):  
Vijaya Vemani ◽  
Mounika P ◽  
Poulami Das ◽  
Anand Kumar Tengli
Keyword(s):  
Amino Acids ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Amino Acid Content ◽  
Building Blocks ◽  
Fruit Juices ◽  
The Body ◽  
Total Amino Acid ◽  
Analytical Approaches

In the preservation of normal physiological functions, the building blocks of the body called amino acids play a crucial role. A number of valuable and nutritional phytoconstituents are contained in fruit juices, such as vitamins, minerals, microelements, organic acids, antioxidants, flavonoids, amino acids and other components. Due to the growing population and demand, the quality of fruit juices is decreasing. One of the unethical and harmful practices called adulteration or food fraudulence has been adopted by most food and beverage industries. The amino acids which is one of the most important phytochemicals of fruit and fruit juices which affects the organoleptic properties like color, odor, and taste of juices and also helps in authenticity process from governing bodies by providing total amino acid content. Consequently, the main aim of the present review work is to provide information regarding the importance of amino acids, how they are adulterated, the potential analytical approach to detected amino acids and which methods are generally accepted method by the food industries. According to the literature review, we presume that reverse phased high-performance liquid chromatography with pre-column derivatization was the most adopted method for quality checking due to its advantages over other old and recent analytical approaches like simple, rapid, cost-effective nature, less / no sample matrix effect with high sensitivity, accuracy, and precision.

scholarly journals Chemical composition and nutritional quality of short-ripened rennet cheeses produced by traditional methods

2018 ◽  
Vol 74 (10) ◽  
pp. 5971-2018 ◽  
Author(s):  
PRZEMYSŁAW KNYSZ ◽  
MICHAŁ GONDEK ◽  
RENATA PYZ-ŁUKASIK ◽  
MONIKA ZIOMEK ◽  
ŁUKASZ DROZD ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Chemical Composition ◽  
G Protein ◽  
Nutritive Value ◽  
Salt Content ◽  
Amino Acid Content ◽  
Traditional Methods ◽  
Dairy Starter Cultures ◽  
Limiting Amino Acids

The aim of the study was to determine the variability in the chemical composition and nutritive value parameters of smoked and unsmoked short-ripened rennet cheeses and unsmoked long-ripened rennet cheeses produced by traditional methods. The raw material for the production of short-ripened cheeses was pasteurized cows’ milk obtained from a dairy, whereas the long-ripened cheeses were manufactured from raw cows’ milk obtained from the producer’s farm. All three varieties of cheese examined were produced with commercial dairy starter cultures. The material for the study was collected in winter, directly at the producers’ retail outlets in southern and eastern Poland. The basic chemical composition was determined according to the Polish Standards, whereas the amino acid profiles of proteins from the cheeses were determined by ion-exchange chromatography. The result analysis revealed significant differences between the different varieties of cheese in terms of their water content, ranging from 32.2% to 42.1%, as well as protein content, which varied from 25.6% to 31.6%. Fat levels ranged between 22.2% and 24%, whereas total ash content amounted to 5.1-5.8%. The significantly highest salt content was found in unsmoked short-ripened cheeses. In all three cheese varieties, the total exogenous amino acid content was comparable, ranging from 46.17 g to 47.36 g/100 g protein, and that of endogenous amino acids varied from 52 g to 53 g/100 g protein. The biological value of proteins was determined by calculating to the chemical score (CS), as described by Mitchell and Block, and the essential amino acid index (EAAI), as described by Oser. A comparison of the results with the standard chicken egg white proteins showed that the limiting amino acids for all varieties of cheese were methionine and cysteine. On the other hand, a comparison with the FAO/WHO-suggested pattern of amino acid requirements (1991) for all age groups over 1 year of age showed that the limiting amino acids were methionine and cysteine in smoked and unsmoked short-ripened cheeses, and treonine in long-ripened cheeses. Considering the chemical indices, such as CS and EAAI, it may be concluded that the traditional rennet cheeses produced in southern and eastern Poland have a favourable amino acid composition of proteins and a high nutritive value..

scholarly journals Unusual Aggregation Properties of Single Amino Acid L-Lysine Hydrochloride

2021 ◽  
Author(s):  
Bharti Koshti ◽  
Ramesh Singh ◽  
Vivekshinh Kshtriya ◽  
Shanka Walia ◽  
Dhiraj Bhatia ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Self Assembly ◽  
Short Term Memory ◽  
Deionized Water ◽  
The Body ◽  
The Self ◽  
Single Amino Acid ◽  
Maple Syrup ◽  
Self Assembling

<p>.<br></p><p>The self-assembly of single amino acids is very important topic of research since there are plethora of diseases like phenylketonuria, tyrosinemia, hypertryptophanemia, hyperglycinemia, cystinuria and maple syrup urine disease to name a few which are caused by the accumulation or excess of amino acids. These are in-born errors of metabolisms (IEM’s) which are caused due to the deficiency of enzymes involved in catabolic pathways of these enzymes. Hence, it is very pertinent to understand the fate of these excess amino acids in the body and their self-assembling behaviour at molecular level. From the previous literature reports it may be surmised that the single amino acids like Phenylalanine, Tyrosine, Tryptophan, Cysteine and Methionine assemble to amyloid like structures, and hence have important implications in the pathophysiology of IEM’s like phenylketonuria, tyrosinemia, hypertryptophanemia, cystinuria and hypermethioninemia respectively. In this manuscript we report the self-assembly of lysine hydrocholride to fiber like structures in deionized water. It could be observed that lysine assemble to globular structures in fresh condition and then gradually changes to fiber like morphologies by self-association over time after 24 hours. These fibers gradually change to tubular morphologies after 3 day followed by fractal irregular morphologies in 10 and 15 days respectively. Notably, lysine exists as positively charged amino acid at physiological pH and the amine groups in lysine remain protonated. Hence, the self-assembling properties of lysine hydrochloride in deionized water is also pertinent and give insights into the fate of this amino acid in body in case it remains unmetabolized. Further, MTT assays were done to analyse the toxicities of these aggregates and the assay suggest their cytotoxic nature on SHSY5Y neural cell lines. Hence, the aggregation of lysine may be attributed to the pathological symptoms caused in diseases like hyperlysinemia which is associated with the neurological problems like seizures and short-term memory as observed in case of amyloid diseases like Parkinson’s and Alzheimer’s to name a few.</p>

Consistency and Change

2019 ◽  
Author(s):  
Alan Kelly
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Living Organism ◽  
Peptide Bond ◽  
The Body ◽  
Blood Proteins ◽  
Genes Encoding ◽  
Fundamental Phenomenon ◽  
P Proteins

Proteins are, in my view, the most impressive molecules in food. They influence the texture, crunch, chew, flow, color, flavor, and nutritional quality of food. Not only that, but they can radically change their properties and how they behave depending on the environment and, critically for food, in response to processes like heating. Even when broken down into smaller components they are important, for example giving cheese many of its critical flavor notes. Indeed, I would argue that perhaps the most fundamental phenomenon we encounter in cooking or processing food is the denaturation of proteins, as will be explained shortly. Beyond food, the value of proteins and their properties is widespread across biology. Many of the most significant molecules in our body and that of any living organism (including plants and animals) are proteins. These include those that make hair and skin what they are, as well as the hemoglobin that transports oxygen around the body in our blood. Proteins are built from amino acids, a family of 20 closely related small molecules, which all have in chemical terms the same two ends (chemically speaking, an amino end and an acidic end, hence the name) but differ in the middle. This bit in the middle varies from amino acid to amino acid, from simple (a hydrogen atom in the case of glycine, the simplest amino acid) to much more complex structures. Amino acids can link up very neatly, as the amino end of one can form a bond (called a peptide bond) with the acid end of another, and so forth, so that chains of amino acids are formed that, when big enough (more than a few dozen amino acids), we call proteins. Our bodies produce thousands of proteins for different functions, and the instructions for which amino acids combine to make which proteins are essentially what the genetic code encrypted in our DNA specifies. We hear a lot about our genes encoding the secrets of life, but what that code spells is basically P-R-O-T-E-I-N. Yes, these are very important molecules!

scholarly journals Conversion Percentage of Tryptophan to Nicotinamide is Higher in Rice Protein Diet than in Wheat Protein Diet in Rats

2015 ◽  
Vol 8 ◽  
pp. IJTR.S22444
Author(s):  
Katsumi Shibata ◽  
Tsutomu Fukuwatari ◽  
Tomoyo Kawamura
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Body Weight Gain ◽  
Acid Value ◽  
Amino Acid Mixture ◽  
The Body ◽  
Protein Diet ◽  
Acid Mixture ◽  
Wheat Protein ◽  
Rice Protein

We reported previously that the pellagragenic property of corn protein is not only low L-tryptophan concentration but also the lower conversion percentage of L-tryptophan to nicotinamide; the amino acid composition greatly affected the conversion percentage. The amino acid value of wheat protein is lower than that of rice protein. In the present study, we compare the conversion percentages of L-tryptophan to nicotinamide between wheat protein and rice protein diets in growing rats. The body weight gain for 28 days in rats fed with a 10% amino acid mixture diet with wheat protein was lower than that of rats fed with a 10% amino acid diet with rice protein (68.1 ± 1.6 g vs 108.4 ± 1.9 g; P < 0.05). The conversion percentage of L-tryptophan to nicotinamide was also lower for the wheat protein diet compared with the rice protein diet (1.44 ± 0.036% vs 2.84 ± 0.19%; P < 0.05). The addition of limiting amino acids (L-isoleucine, L-lysine, L-tryptophan, L-methionine, L-threonine) to the wheat protein diet improved growth and the conversion percentage. In conclusion, our result supports the thinking that the composition of amino acids affects the conversion ratio of L-tryptophan to nicotinamide.

scholarly journals In vivo Determination of Amino Acid Bioavailability in Humans and Model Animals

2005 ◽  
Vol 88 (3) ◽  
pp. 923-934 ◽  
Author(s):  
Malcolm F Fuller ◽  
Daniel Tomé
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
The Body ◽  
Whole Body ◽  
Intestinal Lumen ◽  
Stable Isotope Labelling ◽  
Ileal Digestibility ◽  
Hydrolyzed Protein ◽  
Protein Free Diet

Abstract Because the digestion of many dietary proteins is incomplete, and because there is a continuous (but variable) entry into the intestinal lumen of endogenous protein and amino acid nitrogen that is also subject to digestion, the fluxes of nitrogen, amino acids, and protein in the gut exhibit a rather complicated pattern. Methods to distinguish and quantitate the endogenous and dietary components of nitrogen and amino acids in ileal chyme or feces include the use of a protein-free diet, the enzyme-hydrolyzed protein method, different levels of protein intake, multiple regression methods, and stable-isotope labelling of endogenous or exogenous amino acids. Assessment of bioavailability can be made, with varying degrees of difficulty, in man directly but, for routine evaluation of foods, the use of model animals is attractive for several reasons, the main ones being cost and time. Various animals and birds have been proposed as models for man but, in determining their suitability as a model, their physiological, enzymological, and microbiological differences must be considered. Fecal or ileal digestibility measurements, as well as apparent and true nitrogen and amino acid digestibility measurements, have very different nutritional significance and can, thus, be used for different objectives. Measurements at the ileal level are critical for determining amino acid losses of both dietary and endogenous origin, whereas measurements at the fecal level are critical in assessing whole-body nitrogen losses. A complementary and still unresolved aspect is to take into account the recycling of intestinal nitrogen and bacterial amino acids to the body.

scholarly journals The metabolic utilization of amino acids: potentials of 14CO2 breath test measurements

1992 ◽  
Vol 67 (2) ◽  
pp. 207-214 ◽  
Author(s):  
V. V. A. M. Schreurs ◽  
H. A. Boekholt ◽  
R. E. Koopmanschap ◽  
P. J. M. Weijs
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Breath Test ◽  
Relative Rate ◽  
The Body ◽  
Adult Rats ◽  
Total Oxidation ◽  
Amino Acid Utilization ◽  
Amino Acid Requirements ◽  
14Co2 Breath Test

The present paper offers a dual 14CO2 breath test approach to study the metabolic utilization of free amino acids in the body. Using the carboxyl-[14C]isotopomer of an amino acid as the test substrate the percentage recovery of the isotope as 14CO2 reflects which part of the labelled amino acid flux has been decarboxylated. The residual C fragments may flow to total oxidation at least to the level recovered for the universal [14C]isotopomer. In the case that recovery for total oxidation is less than for decarboxylation, part of the [14C]fragments are retained in the body by either exchange or non-oxidative pathways. Utilization of tyrosine and leucine was measured in the post-absorptive phase in adult rats conditioned on isoenergetic diets containing 210, 75 or 0 g protein/kg. It was shown that the level of dietary protein exerts an influence on both decarboxylation and total oxidation. Although the responses of leucine and tyrosine were not different for total oxidation, there was a difference between the amino acids in their relative rate of decarboxylation. That this dual 14CO2 breath test approach can be used as a tool to evaluate whether the protein and amino acid supply has been adequate to support actual requirements is discussed.Amino acid utilization: Amino acid requirements: Leucine: Tyrosine

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