Cysteine is a nonessential amino acid, and is synthesized from homocysteine, which is itself synthesized from the metabolism of methionine. This product has one of the fastest drying times in the game; it only takes 15 minutes after application to be ready for sanding and staining. For more recent exchange rates, please use the Universal Currency Converter. While this is elmers carpenters wood filler natural vectors small Elmers Carpenters Wood Filler White Cell proportion of total elemrs expenditure, small increases in this value can impact body weight. For example, EAA density is about equal to or greater than the density of essential amino acids present in a full-length reference nutritional polypeptide, such as nstural lactoglobulin, bovine beta-casein or bovine type I collagen, e. In some embodiments the fragment comprises at least 50 amino acids.

Pros Quick set time Extremely strong Accepting of sanding and painting High quality Ideal for heavy-duty repairs Cons Does not allow you a lot of working time 4.

FamoWood Latex Wood Filler. The FamoWood is one of the most versatile wood fillers on the market today. It comes in a variety of colors that match several natural wood tones.

This means that you might not even have to sand or paint in some instances. This stainable wood filler is also extremely strong, thus allowing you to use it for larger, heavy-duty repairs.

Moreover, thanks to its solvent-free nature, it has very little odor, thus making it easy to work with. However, solvents are utilized in wood fillers for good reason. They increase the shelf life of a product by rejuvenating it once it dries out. As such, due to being solvent-free, the FamoWood might not have as long a shelf life.

Nonetheless, its strength is not compromised. However, make sure that you press the lid tightly when closing the container, or you will risk having the entire container dry out. All in all, it is a highly effective stainable wood filler that will make quick work of your major dents. Pros Comes in various wood tones Sets fast Extremely strong Does not have a strong odor Effective for both indoor and outdoor use Cons The entire product can dry out if you do not close the lid properly 5.

Minwax Stainable Wood Filler. This is yet another great product to consider if you are looking for a fast-drying stainable wood filler. The Minwax dries so fast that you can start sanding and staining the fixed area within minutes of application. As such, it is an excellent solution when looking to fix something in a rush. Nonetheless, like all other fillers, it takes several hours for the product to cure. While this product works for most wood types, it is best suited for water-based wood stains and oily surfaces, meaning that you can use it for both indoor and outdoor purposes.

Be careful when using it because it dries so fast, and be sure to seal the unused filler correctly to prevent the entire product from drying up. The Minwax is a fantastic wood filler that has no qualms accepting stains. It also features an attractive price point making for a great purchase. Pros Ideal for heavy-duty applications Can be used both indoors and outdoors Dries fast Affordable Cons The entire product can dry if left unsealed 6.

Timbermate Hardwood Wood Filler. This stainable wood filler from Timbermate is another high-quality product that should suit the needs of most users perfectly. It does an excellent job fixing cracks, scratches, and holes in beech, pine, maple, and other hardwood fixtures.

You can also use it as a grain filler. In addition to enhancing the natural integrity of wood, this filler is also long-lasting and does not crack or shrink with time. You will also appreciate the fast drying nature of this product.

It dries fully within 20 to 30 minutes of application, to allow you to sand and paint or stain over it. It can also accept screws and nails if your project calls for it. Moreover, thanks to being water-based, this product is free of acrylic, latex, or any other solvents that make other fillers dangerous to handle without gloves.

And if it dries out, you can use water to soften it up. The DAP is an excellent choice for anyone looking for a stainable heavy-duty wood filler.

This stuff dries fast to leave behind a rock hard filling to ensure that you do not have to worry about making another repair for a long time to come. In addition to being easy to work with, this product is also highly accepting of sanding and staining, thus ensuring a smooth finish. It is also a highly versatile wood filler, as it can be used across a wide range of surfaces.

Thanks to its water-soluble formula, the DAP has an incredibly long shelf life. This means that you can reactivate the leftover product using water to use in another application. However, this also means that it is not an ideal filler for outdoor use. Varathane Wood Filler. Lastly, we have the stainable wood filler from Varathane. While not as strong as the other products on this list, it is still reliable for making small indoor fixes.

Due to its water-soluble nature, this product is not recommended for outdoor use. The Varathane is easy to use in addition to being non-toxic, thus making it a good choice for beginners. Moreover, while one hour of drying time is not record-breaking, it is still reasonable.

The Varathane is accepting of sanding and other preparation techniques for staining, and you can even use nails and screws once it cures. This wood filler finds its best use fixing scratches, gouges, and small holes in cabinets, furniture, trims, and wood floors. Wood fillers are designed differently; some work better with stain and others with paint. Using the wrong product could end up ruining your entire project.

As such, evaluate a potential product to ensure that it is rated for staining. Still, some products will give you better results than others. These fillers have water as their primary base, meaning that they need it for activation. They typically contain cellulose, gypsum, or wood fiber in their formula. The great thing about water-based formulas is that they have a long shelf life.

Moreover, they are typically non-toxic, thus making them safe to use. They also do not emit odors, thereby making them ideal for indoor use.

These filers usually have high amounts of organic solvents in their formula. You can tell that a filler is solvent-based based on its smell. These have a characteristic strong smell that can be overpowering.

However, solvent-based wood fillers are stronger than water-based fillers. Additionally, they are highly resistant to temperature extremes and humidity. As a result, they are more suited for heavy-duty outdoor projects.

Therefore, the choice between a solvent-based and water-based filler will be entirely dependent on your needs. When looking for a wood filler, it is recommended to choose one that comes in bulk packaging. Small containers and tubes will not cover anything beyond small holes and cracks. Moreover, they do not give you good value for money. Nonetheless, if it is a one-off blemish that you are trying to fix, a small-quantity product should suffice.

However, for heavy-duty or professional projects, purchase in larger quantities to ensure that you do not run out of product while working. Moreover, this ensures that you will always have something in your emergency kit in case of accidents. Fillers have different drying times. While a product with a fast drying time sounds like an excellent solution, there are instances you would prefer one that is slow to dry.

For example, when working on a larger project, you do not want to be in a rush against time. During such an instance, you might want that dries slower. There are several stainable wood filling products on the market today, and they come with different properties, giving each unique benefits.

Therefore, the best stainable wood filler will depend on your needs or requirements. The most important thing is to make sure that a filler is stainable before you start evaluating it based off other factors. Fortunately, the products featured in these reviews are some of the best stainable wood fillers on the market today.

This product can be used across a wide array of wood surfaces, in addition to being non-toxic and easy to use. Its friendly price point is what sealed the deal for us. What has held you back from getting an impact wrench? Adam Harris Last updated: November 25, Check Latest Price. Changes color when dry Low odor and toxicity Water-soluble Easy to sand, paint, and stain Cost-friendly. Not the strongest filler. Water-soluble nature allows it to rehydrate even after curing 1-year money-back guarantee Handles temperature extremes well Easy to sand, stain, and pain Great value for price.

For example, PTMs include addition, removal or redistribution of biotinylation, pegylation, acylation, alkylation, butyrylation, glycosylation, hydroxylation, iodination, oxidation, propionylation, malonylation, myristoylation, palmitoylation, isoprenylation, succinylation, selenoylation, SUMOylation, ubiquitination, and glypiation removal or redistribution of disulfide bridges.

In those embodiments it is understood that the two measures are not completely equivalent, but it is also understood that the measures result in measurements that are similar enough to use for this purpose.

Even so, the skilled artisan understands that this is a useful comparison. If provided with the total number of amino acid residues present in the protein of interest the skilled artisan can also determine the weight proportion of branched chain amino acid residues in the protein of interest.

In some embodiments a protein according to this disclosure comprises a first polypeptide sequence comprising a fragment of an edible species polypeptide. In some embodiments of the nutritrive protein, the protein consists of the first polypeptide sequence. In some embodiments of the nutritrive protein, the protein consists of the fragment of an edible species polypeptide. In some embodiments a protein according to this disclosure comprises a first polypeptide sequence that comprises ratio of branched chain amino acid residues to total amino acid residues that is equal to or greater than the ratio of branched chain amino acid residues to total amino acid residues present in at least one of whey protein, egg protein, and soy protein.

In some embodiments a protein according to this disclosure comprises a first polypeptide sequence that comprises a ratio of L leucine residues to total amino acid residues that is equal to or greater than the ratio of L residues to total amino acid residues present in at least one of whey protein, egg protein, and soy protein. In some embodiments a protein according to this disclosure comprises a first polypeptide sequence that comprises a ratio of essential amino acid residues to total amino acid residues that is equal to or greater than the ratio of essential amino acid residues to total amino acid residues present in at least one of whey protein, egg protein, and soy protein.

In some embodiments the protein comprises a first polypeptide sequence that comprises a ratio of branched chain amino acid residues to total amino acid residues that is equal to or greater than the ratio of branched chain amino acid residues to total amino acid residues present in at least one of whey protein, egg protein, and soy protein; and comprises a first polypeptide sequence that comprises a ratio of essential amino acid residues to total amino acid residues that is equal to or greater than the ratio of essential amino acid residues to total amino acid residues present in at least one of whey protein, egg protein, and soy protein.

In some embodiments the protein comprises a first polypeptide sequence that comprises a ratio of L leucine residues to total amino acid residues that is equal to or greater than the ratio of L residues to total Elmers Carpenters Wood Filler Sds Version amino acid residues present in at least one of whey protein, egg protein, and soy protein; and comprises a first polypeptide sequence that comprises a ratio of essential amino acid residues to total amino acid residues that is equal to or greater than the ratio of essential amino acid residues to total amino acid residues present in at least one of whey protein, egg protein, and soy protein.

Provided are nutritive polypeptides that are nutritionally complete. In some embodiments of the protein, the first polypeptide sequence comprises a first polypeptide sequence that contains at least one of every essential amino acid. In some embodiments, a glycan is linked covalently or non-covalently to the polypeptide. In some embodiments the linkage occurs via a glycosidic bond. In some embodiments, the linkage is directly between the glycan or glycoyl and polypeptide or via an intermediary molecule.

In some embodiments, the glycosidic bond is N-linked or O-linked. In some embodiments, the polysaccharide or oligosaccharide has a linear or branched structure. In some embodiments, the monosaccharide units comprise N-acetyl galactosamine, N-acetylglucosamine, galactose, neuraminic acid, fructose, mannose, fucose, glucose, xylose, N-acetylneuraminic acid, N-glycolylneuraminic acid, O-lactyl-N-acetylneuraminic acid, O-acetyl-N-acetylneuraminic acid, or O-methyl-N-acetylneuraminic acid.

In some embodiments, the monosaccharide is modified by a phosphate, sulfate, or acetate group. In some embodiments the acceptor site consists of a nucleophilic acceptor of a glycosidic bond. In some embodiments, the nucleophilic acceptor site consists of an amino group. In some embodiments the amino acid consists of an asparagine, arginine, serine, threonine, hydroxyproline, hydroxylysine, tryptophan, phosphothreonine, serine, or phosphoserine.

In some embodiments the amino acid for the exogenous glycosylation acceptor site did not carry a glycan or glycoyl in the native composition.

In some embodiments, the amino acid does not occur in the primary sequence of the polypeptide in the native composition. In some embodiments, the glycosylation acceptor site is an exogenous glycosylation site or a native glycosylation site.

Disclosed herein are formulations containing isolated nutritive polypeptides at least one exogenous glycosylation acceptor site present on an amino acid of the nutritive polypeptide. In some aspects, the at least one exogenous glycosylation acceptor site is occupied by an exogenous glycoyl or glycan, or alternatively, is unoccupied or is occupied by a non-natively occupying glycol or glycan. The amino acids, e. Exemplary glycans are N-acetyl galactosamine, N-acetylglucosamine, galactose, neuraminic acid, fructose, mannose, fucose, glucose, xylose, N-acetylneuraminic acid, N-glycolylneuraminic acid, O-lactyl-N-acetylneuraminic acid, O-acetyl-N-acetylneuraminic acid, and O-methyl-N-acetylneuraminic acid.

In some embodiments provided are formulations containing a nutritive polypeptide that is identical to the amino acid sequence of a polypeptide in a reference edible species glycoprotein, but the carbohydrate component of the nutritive polypeptide differs from a carbohydrate component of the reference edible species glycoprotein. The nutritive polypeptide is produced, for example, by expressing the polypeptide of the reference glycoprotein in a non-native host such as Aspergillus, Bacillus, Saccharomyces or a mammalian cell.

The nutritive polypeptide variant is created by the insertion, deletion, substitution, or replacement of amino acid residues in the amino acid sequence of the polypeptide of the reference glycoprotein.

Preferably, the nutritive polypeptide has distinguishable chemical, biochemical, biophysical, biological, or immunological properties from the reference glycoprotein. For example, the nutritive polypeptide is more hygroscopic, hydrophilic, or soluble in aqueous solutions than the reference glycoprotein. Alternatively, the nutritive polypeptide is less hygroscopic, hydrophilic, or soluble in aqueous solutions than the reference glycoprotein.

In another example, the nutritive polypeptide is more antigenic, immunogenic, or allergenic than the reference glycoprotein, or alternatively, the nutritive polypeptide is less antigenic, immunogenic, or allergenic than the reference glycoprotein.

The nutritive polypeptide is more stable or resistant to enzymatic degradation than the reference glycoprotein or the nutritive polypeptide is more unstable or susceptible to enzymatic degradation than the reference glycoprotein. The carbohydrate component of the nutritive polypeptide is substantially free of N-glycolylneuraminic acid or has reduced N-glycolylneuraminic acid in comparison to the reference glycoprotein. Alternatively, the carbohydrate component of the nutritive polypeptide has elevated N-glycolylneuraminic acid in comparison to the reference glycoprotein.

Three natural sources of protein generally regarded as good sources of high quality amino acids are whey protein, egg protein, and soy protein. Each source comprises multiple proteins. Table RNP2 presents the weight proportion of each protein source that is essential amino acids, branched chain amino acids L, I, and V , and leucine L alone.

The sources relied on to determine the amino acid content of Whey are: Belitz H. Food Chemistry 4th Ed. Springer-Verlag, Berlin Heidelberg ; gnc. The source for soy protein is Self Nutrition Data nutritiondata. According to the USDA nutritional database whey can include various non-protein components: water, lipids such as fatty acids and cholesterol , carbohydrates and sugars, minerals such as Ca, Fe, Mg, P, K, Na, and Zn , and vitamins such as vitamin C, thiamin, riboflavin, niacin, vitamin B-6, folate, vitamin B, and vitamin A.

According to the USDA nutritional database egg white can include various non-protein components: water; lipids, carbohydrates, minerals such as Ca, Fe, Mg, P, K, Na, and Zn , and vitamins such as thiamin, riboflavin, niacin, vitamin B-6, folate, and vitamin B According to the USDA nutritional database soy can include various non-protein components: water, lipids such as fatty acids , carbohydrates, minerals such as Ca, Fe, Mg, P, K, Na, and Zn , and vitamins such as thiamin, riboflavin, niacin, vitamin B-6, folate.

In some embodiments a protein comprises or consists of a derivative or mutein of a protein or fragment of an edible species protein or a protein that naturally occurs in a food product. Typically the ratio of at least one of branched chain amino acid residues to total amino acid residues, essential amino acid residues to total amino acid residues, and leucine residues to total amino acid residues, present in the engineered protein or a first polypeptide sequence thereof is greater than the corresponding ratio of at least one of branched chain amino acid residues to total amino acid residues, essential amino acid residues to total amino acid residues, and leucine residues to total amino acid residues present in the reference protein or polypeptide sequence.

In another aspect, provided are nutritive polypeptides that contain amino acid sequences homologous to edible species polypeptides, which are optionally secreted from unicellular organisms and purified therefrom. Such nutritive polypeptides can be endogenous to the host cell or exogenous, can be naturally secreted in the host cell, or both, and can be engineered for secretion. Also provided are orthologs of nutritive polypeptides.

In some embodiments herein a nutritive polypeptide contains a fragment of an edible species polypeptide. In some embodiments the fragment comprises at least 25 amino acids. In some embodiments the fragment comprises at least 50 amino acids. In some embodiments the fragment consists of at least 25 amino acids.

In some embodiments the fragment consists of at least 50 amino acids. In some embodiments an isolated recombinant protein is provided. In some embodiments the protein comprises a first polypeptide sequence, and the first polypeptide sequence comprises a fragment of at least 25 or at least 50 amino acids of an edible species protein.

In some embodiments the proteins is isolated. In some embodiments the proteins are recombinant. In some embodiments the proteins comprise a first polypeptide sequence comprising a fragment of at least 50 amino acids of an edible species protein. In some embodiments the proteins are isolated recombinant proteins. In some aspects, a protein or fragment thereof includes at least two domains: a first domain and a second domain. One of the two domains can include a tag domain, which can be removed if desired.

Each domain can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or greater than 25 amino acids in length. For example, the first domain can be a polypeptide of interest that is 18 amino acids in length and the second domain can be a tag domain that is 7 amino acids in length. As another example, the first domain can be a polypeptide of interest that is 17 amino acids in length and the second domain can be a tag domain that is 8 amino acids in length.

In some embodiments herein a fragment of an edible species polypeptide is selected and optionally isolated. In some aspects the nutritive polypeptide is substantially digestible upon consumption by a mammalian subject. Preferably, the nutritive polypeptide is easier to digest than at least a reference polypeptide or a reference mixture of polypeptides, or a portion of other polypeptides in the consuming subject's diet.

For example, a nutritive polypeptide is easier to digest if it has a half-life in the gastrointestinal tract of a human subject of less than 60 minutes, or less than 50, 40, 30, 20, 15, 10, 5, 4, 3, 2 minutes or 1 minute. In certain embodiments the nutritive polypeptide is provided in a formulation that provides enhanced digestion; for example, the nutritive polypeptide is provided free from other polypeptides or other materials. In some embodiments, the nutritive polypeptide contains one or more recognition sites for one or more endopeptidases.

In a specific embodiment, the nutritive polypeptide contains a secretion leader or secretory leader sequence, which is then cleaved from the nutritive polypeptide.

In some embodiments, the nutritive polypeptide is susceptible to cleavage by one or more exopeptidases. Digestibility is a parameter relevant to the benefits and utility of proteins.

Information relating to the relative completeness of digestion can serve as a predictor of peptide bioavailability Daniel, H. Annual Review of Physiology, Volume 66, pp. In some embodiments proteins disclosed herein are screened to assess their digestibility. Digestibility of proteins can be assessed by any suitable method known in the art. In some embodiments digestibility is assessed by a physiologically relevant in vitro digestion reaction that includes one or both phases of protein digestion, simulated gastric digestion and simulated intestinal digestion see, e.

Stability of the major allergen Brazil nut 2S albumin Ber e 1 to physiologically relevant in vitro gastrointestinal digestion. FEBS Journal, pp. Journal of Agricultural and food chemistry, pp. Phospholipid interactions protect the milk allergen a-Lactalbumin from proteolysis during in vitro digestion. Journal of agricultural and food chemistry, pp.

Disintegration of Solid Foods in Human Stomach. Journal of Food Science, pp. Samples at different stages of the digestion e. The disappearance of protein over time indicates the rate at which the protein is digested in the assay.

This assay can be used to assess comparative digestibility i. In some embodiments the digestibility of the protein is higher i. In some embodiments the protein is not detectable in one or both of the SGF and SIF assays by 2 minutes, 5 minutes, 15 minutes, 30 minutes, 60 minutes, or minutes. In such embodiments the rate of digestion of the protein may not be optimized for the highest possible rate of digestion.

In such embodiments the rate of absorption of the protein following ingestion by a mammal can be slower and the total time period over which absorption occurs following ingestion can be longer than for proteins of similar amino acid composition that are digested at a faster initial rate in one or both of SGF and SIF. In some embodiments the protein is completely or substantially completely digested in SGF.

In some embodiments the protein is substantially not digested or not digested by SGF; in most such embodiments the protein is digested in SIF. Assessing protein digestibility can also provide insight into a protein's potential allergenicity, as proteins or large fragments of proteins that are resistant to digestive proteases can have a higher risk of causing an allergenic reaction Goodman, R.

Allergenicity assessment of genetically modified crops—what makes sense? Nature Biotechnology, pp. To detect and identify peptides too small for chip electrophoresis analysis, liquid chromatography and mass spectrometry can be used. In some embodiments digestibility of a protein is assessed by identification and quantification of digestive protease recognition sites in the protein amino acid sequence. In some embodiments the protein comprises at least one protease recognition site selected from a pepsin recognition site, a trypsin recognition site, and a chymotrypsin recognition site.

In some embodiments it is a peptide bond after i. In some embodiments it is a peptide bond after an amino acid residue selected from Lys or Arg, provided that the following residue is not a proline. In some embodiments it is a peptide bond after an amino acid residue selected from Phe, Trp, Tyr, and Leu.

Disulfide bonded cysteine residues in a protein tend to reduce the rate of digestion of the protein compared to what it would be in the absence of the disulfide bond. For example, it has been shown that the rate of digestion of the protein b-lactoglobulin is increased when its disulfide bridges are cleaved I. Reddy, N. Kella, and J. Food Chem. Accordingly, digestibility of a protein with fewer disulfide bonds tends to be higher than for a comparable protein with a greater number of disulfide bonds.

In some embodiments the proteins disclosed herein are screened to identify the number of cysteine residues present in each and in particular to allow selection of a protein comprising a relatively low number of cysteine residues.

For example, edible species proteins or fragments can be identified that comprise a no Cys residues or that comprise a relatively low number of Cys residues, such as 10 or fewer Cys residues, 9 or fewer Cys residues, 8 or fewer Cys residues, 7 or fewer Cys residues, 6 or fewer Cys residues, 5 or fewer Cys residues, 4 or fewer Cys residues, 3 or fewer Cys residues, 2 or fewer Cys residues, 1 Cys residue, or no Cys residues.

In some embodiments 1 Cys residue is deleted or replaced, 1 or more Cys residues are deleted or replaced, 2 or more Cys residues are deleted or replaced, 3 or more Cys residues are deleted or replaced, 4 or more Cys residues are deleted or replaced, 5 or more Cys residues are deleted or replaced, 6 or more Cys residues are deleted or replaced, 7 or more Cys residues are deleted or replaced, 8 or more Cys residues are deleted or replaced, 9 or more Cys residues are deleted or replaced, or 10 or more Cys residues are deleted or replaced.

In some embodiments the protein comprises 10 or fewer Cys residues, 9 or fewer Cys residues, 8 or fewer Cys residues, 7 or fewer Cys residues, 6 or fewer Cys residues, 5 or fewer Cys residues, 4 or fewer Cys residues, 3 or fewer Cys residues, 2 or fewer Cys residues, 1 Cys residue, or no Cys residues.

In some embodiments, the protein comprises 1 or fewer Cys residues. In some embodiments, the protein comprises no Cys residues. Alternatively or in addition, disulfide bonds that are or can be present in a protein can be removed.

Disulfides can be removed using chemical methods by reducing the disulfide to two thiol groups with reducing agents such as beta-mercaptoethanol, dithiothreitol DTT , or tris 2-carboxyethyl phosphine TCEP. Modification of Cysteine. Current Protocols in Protein Science. Disclosed herein are compositions, formulations, and food products that contain viscosity-modulating nutritive polypeptides.

In one aspect, provided are formulations substantially free of non-comestible products that contain nutritive polypeptides present in a nutritional amount, and the nutritive polypeptide decreases the viscosity of a food product. The formulations are incorporated into food products having advantages over similar food products lacking the nutritive polypeptides, or the formulations are incorporated into other products such as beverage products or animal feed products.

Preferably, the nutritive polypeptide is present in the food product such that consumption of a nutritional amount of the food product is satiating.

In an embodiment of the invention, gelatin, an animal-derived material, is replaced by a non-animal derived product, containing one or more nutritive polypeptides.

Typically the nutritive polypeptide is present in an amount effective to replace gelatin in the product. The gelatin replacement is incorporated into a food product, a beverage product, or an animal feed product, and the formulation is substantially free of non-comestible products.

Viscous nutritive polypeptides can be used as a nutritionally favorable low calorie substitute for fat. Additionally, it may be desired to add to the compositions and products one or more polysaccharides or emulsifiers, resulting in a further improvement in the creamy mouthfeel.

In some embodiments, the viscosity of nutritive polypeptide-containing materials is enhanced by crosslinking the nutritive polypeptides or crosslinking nutritive polypeptides to other proteins present in the material. The resulting gel strength and emulsion strength of nutritive polypeptides identified and produced as described herein are examined by preparing a transglutaminase-coupled nutritive protein composition, followed by gel strength and emulsion strength assays.

A suitable transglutaminase derived from microorganisms in accordance with the teachings of U. These commercially available transglutaminases typically have an enzyme activity of about units.

The amount of transglutaminase having an activity of about units added to isolated nutritive polypeptide is expressed as a transglutaminase concentration which is the units of transglutaminase per grams of isolated nutritive polypeptide. The transglutaminase concentration is at least 0. Higher and lower amounts may be used. This enzyme treatment can also be followed by thermal processing to make a viscous solution containing a nutritive polypeptide.

To generate nutritive polypeptide samples containing crosslinks, a sample is mixed with a transglutaminase solution at pH 7. Oscillatory shear measurements can be used to investigate the rheological properties of nutritive polypeptides. Also, to determine the viscosity of nutritive polypeptide solutions and gels viscoelasticity is investigated by dynamic Elmers Carpenters Wood Filler Lowes Jack oscillatory rheometry. A 2 mL sample of nutritive polypeptide solution or nutritive polypeptide solution containing transglutaminase is poured into the Couette-type cylindrical cell 2.

Some samples can be subjected to this thermal treatment after the enzyme treatment. Small deformation shear rheological properties are mostly determined in the linear viscoelastic regime maximum strain amplitude 0. In addition, some small deformation measurements are made as a function of frequency e. Provided are nutritive polypeptides, and compositions and formulations containing nutritive polypeptides, which are useful for the treatment of gastrointestinal tract malabsorption diseases and inflammatory conditions.

The nutritive polypeptides are also useful for treating and preventing loss of muscle mass and muscle function in a subject suffering from a gastrointestinal tract malabsorption disease and inflammatory condition. Moreover, the nutritive polypeptides are further useful for reducing or preventing a side effect meaning a secondary effect, usually undesirable, of a pharmaceutical agent or medical treatment of other therapeutic or prophylactic regimens for gastrointestinal tract malabsorption diseases, as such regimens may result in decreased amino acid availability to the subject, in addition to causing loss of muscle mass and muscle function.

Gastrointestinal diseases affect an estimated 60 to 70 million subjects in the United States. Gastrointestinal tract malabsorption diseases may include, for example, structural defects, and malabsorption caused by infection, drugs, surgical procedures such as bariatric surgery , mucosal abnormalities, inflammation, enzyme deficiency, radiation, digestive failures, systemic diseases, or other causes. Centers for Disease Control and Prevention and over , deaths annually. National Institutes of Health, U.

Department of Health and Human Services. Bethesda, Md. NIH Publication Adequate treatment regimens do not exist to treat and prevent gastrointestinal diseases or the gastrointestinal malabsorption associated with them. Gastrointestinal diseases therefore represent a significant morbidity, mortality and health economic burden.

By way of non-limiting example, a human subject may suffer from or be at risk of a gastrointestinal protein malabsorption disease due to an infection. Exemplary infections include viral infections, bacterial infections, and other parasitic infections, which cause or exacerbate diseases including HIV related malabsorption, Traveler's diarrhea, Tropical sprue, Whipple's disease, Intestinal tuberculosis, and hepatitis. A human subject may suffer from or be at risk of a gastrointestinal protein malabsorption disease due to structural complications of the GI tract or inflammatory diseases or resulting from gastrointestinal reparative surgery.

In addition, a human subject may suffer from or be at risk of a gastrointestinal protein malabsorption disease due to enzymatic deficiencies. Exemplary diseases include Intestinal Enteropeptidase deficiency, Enterokinase deficiency, Zollinger-Ellison syndrome, Pancreatic enzyme deficiency, Lactase deficiency inducing lactose intolerance constitutional, secondary, congenital ; Sucrose intolerance; Intestinal Disaccharidase deficiency. A human subject may suffer from or be at risk of a gastrointestinal protein malabsorption disease due to other systemic disease states.

Exemplary diseases include Hypothyroidism and Hyperthyroidism, Addison's disease, Diabetes mellitus, Hyperparathyroidism and Hypoparathyroidism, Carcinoid syndrome, Protein Malnutrition Hypoproteinemia, Anemia, edema, asthenia, alopecia, hypoalbuminemia , Fiber Deficiency, Abeta-lipoproteinaemia, amyloidosis, Proctitis, Gastroesophageal reflux disease, Pancreatitis, Porphyria, Lysinuric protein intolerance, Shwachman-Diamond syndrome.

Further, a human subject may suffer from or be at risk of a gastrointestinal protein malabsorption disease due to eating disorders. Ed Textbook of Gastroenterology. Blackwell Publishing Ltd. Short bowel syndrome SBS can occur congenitally or from surgery to treat diseases such as Crohn's disease, ulcerative colitis, necrotizing enterocolitis or trauma. Since the gastrointestinal tract is the primary absorptive surface for dietary nutrients, a shortened bowel can cause malabsorption of nutrients and fluids, resulting in nutrient deficiencies, severe diarrhea, dehydration, electrolyte imbalances, weight loss, and frequently, a long-term dependence on parenteral nutrition.

Jeppesen, P. Glucagon-like peptide-2 GLP-2 , a peptide hormone, may act to control nutrient absorptive capacity within the bowel. Amino acids also function as signals of nutrient status, and therefore nutritive polypeptides can be used to deliver GLP-2 secretagogues into the gastrointestinal tract.

GLP-2 receptors are found throughout the small and large bowel in humans, mice, marmoset, and rat. GLP-2 is co-secreted with GLP-1 from intestinal L cells in response to nutrient ingestion and acts to maintain epithelial barrier function while increasing crypt cell proliferation and weight gain. Martin, G R.

Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation. World J Gastroenterol. A further example of gastrointestinal malabsorption is eating disorders, including but not limited to anorexia nervosa.

Anorexia is characterized by extreme dietary restriction. Dietary restriction and the resulting reduction in total stomach capacity in these individuals can lead to eventual multi organ failure, Hypothermia, Gastrointestinal complications, Cardiac complications including arrhythmia, bradycardia, hypotension and damaged heart muscle.

Long term side effects of anorexia are significant and debilitating and include osteoporosis, growth arrest, and amenorrhea. See, Katzman, D K. Medical complications in adolescents with anorexia nervosa: a review of the literature. Et al. Audit of digestive complaints and psychopathological traits in patients with eating disorders: A prospective study. Digestive and Liver Disease. Amino acids are key effectors of gut protein turnover, both as constituents of proteins and as regulatory molecules limiting intestinal injury and maintaining intestinal functions.

Low glutamine levels are reported in gastrointestinal malabsorption diseases, e. Crohn's disease See, Sido B, Low intestinal glutamine level and low glutaminase activity in Crohn's disease: a rational for glutamine supplementation? Dig Dis Sci 51 12 Thus, glutamine delivery via nutritive polypeptides is a useful treatment for Crohn's disease and other indications such as IBS See, Zhou Q, MicroRNAa regulates intestinal membrane permeability in patients with irritable bowel syndrome.

Gut 59 6 It has been noted that glutamine supplementation improves gut barrier function in several experimental conditions of injury Amasheh et al. NY Acad. Diseases characterized by inflammation can be treated and prevented with nutritive polypeptides containing levels of certain amino acids, such as arginine, glutamine, or cysteine, or combinations thereof.

Studies in rodents and humans show that supplemental free arginine, administered either orally or parenterally, accelerates wound healing mainly by increasing collagen deposition in wounds.

Arginine enhances wound healing in humans. Further, Arginine improves epithelial reconstitution after intestinal injury. L-arginine uptake by cationic amino acid transporter 2 is essential for colonic epithelial cell restitution. Hasegawa S, Cysteine, histidine and glycine exhibit anti-inflammatory effects inhuman coronary arterial endothelial cells.

Clin Exp Immunol. L-cysteine administration aids in restoring gut immune homeostasis by attenuating inflammatory responses and restores susceptibility of activated immune cells to apoptosis. Kim C J, L-cysteine supplementation attenuates local inflammation and restores gut homeostasis in a porcine model of colitis.

Biochim Biophys Acta. Thus, the gastrointestinal delivery of cysteine in cysteine-containing nutritive polypeptides is useful for prevention of gut inflammation, and for the reduction of gut inflammation and sequelae thereof. Amino acids are organic molecules containing both amino and acid groups. All amino acids have asymmetric carbon except for glycine and all protein amino acids, except proline, have an alpha-carbon bound to a carboxyl group and a primary amino group.

Amino acids exhibit a diverse range of biochemical properties and biological function due to their varying side chains. They are stable in solution at physiological pH, save for glutamine and cysteine. In the context of some proteins, conditional upon the host and translational machinery, amino acids can undergo post-translational modification. This can have significant effects on their bioavailability, metabolic function, and bioactivity in vivo.

Sugar moieties appended to proteins post-translationally may reduce the usefulness of the nutritive proteins by affecting the gastrointestinal release of amino acids and embedded peptides. A comparison of digestion of glycosylated and non-glycosylated forms of the same proteins shows that the non-glycosylated forms are digested more quickly than the glycosylated forms our data. Although over amino acids exist in nature, 20 serve as building blocks in protein.

Non-protein alpha-AAs and non-alpha AAs are direct products of these 20 protein amino acids and play significant roles in cell metabolism. Due to the metabolic reactions of amino acid catabolism that drive the interconversion between amino acids, a subset of II of the 20 standard protein amino acids are considered non-essential for humans because they can be synthesized from other metabolites amino acids, ketones, etc.

Arginine, cysteine, glycine, glutamine, histidine, proline, serine and tyrosine are considered conditionally essential, as they are not normally used in the diet, and are not synthesized in adequate amounts in specific populations to meet optimal needs where rates of utilization are higher than rates of synthesis.

Functional needs such as reproduction, disease prevention, or metabolic abnormalities, however, can be taken into account when considering whether an amino acid is truly non-essential or can be conditionally essential in a population.

The other 9 protein amino acids, termed essential amino acids, are taken as food because their carbon skeletons are not synthesized de novo by the body to meet optimal metabolic requirements: Histidine; Isoleucine; Leucine; Lysine; Methionine; Phenylalanine; Threonine; Tryptophan; and Valine. All 20 protein amino acids and Elmers Carpenters Wood Filler White Kit non-protein metabolites are used for normal cell functionality, and shifts in metabolism driven by changing availability of a single amino acid can affect whole body homeostasis and growth.

Additionally, amino acids function as signaling molecules and regulators of key metabolic pathways used for maintenance, growth, reproduction, immunity. The small intestine is another important site for amino acid catabolism, governing the first pass metabolism and entry of dietary amino acids into the portal vein and into the peripheral plasma.

The high activity of BCAA transaminases in the intestinal mucosa leads to BCAA conversion to branched-chain alpha-ketoacids to provide energy for enterocytes similar as is done in skeletal muscle. Differences in physiological state of muscle and small intestine metabolism have large implications on amino acid biology systemically across tissues in humans.

Amino acids can exist in both L- and D-isoforms, except for glycine non-chiral. Almost all amino acids in proteins exist in the L-isoform, except for cysteine D-cys due to its sulfur atom at the second position of the side-chain, unless otherwise enzymatically postranslationally modified or chemically treated for storing or cooking purposes.

In order to be catabolized, these D enantiomers are transported across the plasma and other biological membranes and undergo D-oxidation or deaminate the amino acid to convert to its alpha-ketoacid or racemization to convert the D-AA to its L-isoform. Alanine is a glucogenic non-essential amino acid due to its ability to be synthesized in muscle cells from BCAAs and pyruvate as part of the glucose-alanine cycle.

This involves a tightly regulated process by which skeletal muscle frees energy from protein stores for the generation of glucose distally in the liver for use by extrahepatic cells including immunocytes and tissues. The resulting stimulation of gluconeogenesis provides a source of energy in the form of glucose during periods of food deprivation. Alanine becomes a very sensitive intermediary to balance the utilization of BCAAs in the muscle for protein production and generation of available energy through gluconeogenesis in the liver.

Furthermore, the alanine induction of gluconeogenesis is integral to support the function of many tissues, not limited to muscle, liver, and immunocytes. Beyond acting as simply an intermediate, however, it also directly regulates activity of a key enzyme in this energy balance, pyruvate kinase.

Alanine has the ability to inhibit pyruvate kinase by facilitating its phosphorylation, slowing glycolysis and driving the reverse reaction of pyruvate to phosphoenolpyruvate PEP for initiation of gluconeogenesis. A lack of ATP-producing substrates, as occurs in a fasted state, can lead to autophagy and the turnover of intracellular protein in the lysosome to provide an energy source.

Low levels of the glucogenic amino acids, including alanine can stimulate hepatic autophagy, leading to degradation of liver function. Beta-cells show increased autophagy when under high fat diet feeding as a response to increased demand for insulin production and protein turnover as the body reacts to rising plasma glucose concentrations. This progression towards increased insulin production in obesity is an early marker for pre-diabetes, an indicator of insulin resistance, and a risk factor for the deterioration of islet beta cell functionality which eventually leads to the onset of diabetes in overweight individuals.

The ability to regulate alanine levels via nutrition may provide a powerful lever for shifting hepatic and beta cell autophagy to perturb impaired insulin metabolism in overweight individuals. Alanine directly produces beta-alanine, important to the biosynthesis of panthothenic acid vitamin b5 , coenzyme A, and carnosine or which it is the rate-limiting precursor.

This buffering is important for maintaining tissue pH in muscle during the breakdown of glycogen to lactic acid. Beta-alanine is also implicated in decreasing fatigue and increasing muscular work done. Carnosine is an antioxidant and transition metal ion-sequestering agent. It acts as an anti-glycating agent by inhibiting the formation of advanced glycation end products AGEs. AGEs are prevalent in diabetic vasculature and contribute to the development of atherosclerosis.

The presence of AGEs in various cells types affect both the extracellular and intracellular structure and function. Golden, A. Advanced Glycosylation End Products, Circulation Also, the accumulation of AGEs in the brain is a characteristic of aging and degeneration, particularly in Alzheimer's disease.

AGE accumulation explains many neuropathological and biochemical features of Alzheimer's disease such as protein crosslinking, oxidative stress, and neuronal cell death. Because of its combination of antioxidant and antiglycating properties, carnosine is able to diminish cellular oxidative stress and inhibit the intracellular formation of reactive oxygen species and reactive nitrogen species.

In states of obesity and diabetes, animals have been shown to exhibit reduced hepatic autophagy, leading to increased insulin resistance. Autophagy is important for maintenance of the ER and cellular homeostasis, which when stressed can lead to impaired insulin sensitivity.

High fat diet feeding in animal models stresses the ER, while leading to depressed hepatic autophagy through over-stimulation of mTORC1, which reinforces the progression towards insulin sensitivity impaired beta cell function in diabetes.

Reducing the level of systemic Alanine provides an opportunity to lower mTORC1 activity and restore healthy levels of autophagy. Arginine is a glucogenic non-essential amino acid, which can be synthesized via glutamate, aspartate, glutamine, and proline. It is produced by the mammalian small intestine via oxidation of glutamate, glutamine, and aspartate, which generates ornithine, citrulline, arginine, and alanine. It can also be produced along with ornithine and citrulline via the proline oxidase pathway from active degradation of proline in enterocytes.

Arginine is converted from citrulline released into circulation by the enterocytes in the kidneys and some endothelial cells leukocytes and smooth muscle. Newborns utilize most of the free citrulline locally in the small intestine for arginine synthesis rather than systemic release.

Arginine and proline oxidation is constrained to the mucosa due to reduced activity of pyrrolinecarboxylate dehydrogenase across the other tissues. Citrulline is produced from arginine as a by-product of a reaction catalyzed by the NOS family.

Dietary supplement of either arginine or citrulline is known to reduce plasma levels of glucose, homocysteine, and asymmetric dimethylarginine, which are risk factors for metabolic syndrome. L-citrulline accelerates the removal of lactic acid from muscles, likely due to the affects on vascular tone and endothelial function.

Recent studies have also shown that L-citrulline from watermelon juice provides greater recovery from exercise, and less soreness the next day. It also appears that delivery of L-citrulline as a free form results in less uptake into cells in vitro than in the context of watermelon juice which contains high levels of L-citrulline. This suggests an opportunity to deliver peptide doses, which can traffic arginine into muscle tissue for conversion into citrulline by eNOS at the endothelial membrane for improved efficacy.

Arginine is a highly functional amino acid implicated in many signaling pathways and as a direct precursor of nitric oxide NO , which facilitates systemic signaling between tissues and regulation of nutrient metabolism and immune function. NO is important for normal endothelial function and cardiovascular health including vascular tone, hemodynamics, and angiogenesis. Arginine supplementation was shown to improve endothelium-dependent relaxation, an indicator of cardiovascular function in type I and type II models of diabetes mellitus.

Notably, arginine supplementation reduced white adipose tissue but increased brown fat mass in Zucker diabetic rats and diet-induced obese rats.

In addition, both skeletal muscle mass and whole body insulin sensitivity were enhanced in response to arginine supplementation via mechanisms involving increases in muscle mTOR and NO signaling. Surprisingly, long-term oral administration of arginine decreased fat mass in adult obese humans with type II diabetes Lucotti et al Moreover, supplementation with arginine to a conventional corn- and soybean-based diet reduced fat accretion and promoted protein deposition in the whole body of growing-finishing pigs.

In a small pilot trial in humans data indicated that defective insulin-mediated vasodilatation in obesity and non-insulin dependent diabetics NIDDM can be normalized by intravenous L-arginine; L-arginine also improved insulin sensitivity in healthy subjects, obese patients and NIDDM patients, indicating a possible mechanism that is different from the restoration of insulin-mediated vasodilatation.

In addition, a chronic administration of L-arginine improved glucose levels, insulin induced-hepatic glucose production, and insulin sensitivity in type II diabetic patients Piatti et al Arginine rich peptides have not been isolated and tested. Arginine is a well-studied secretagogue that can stimulate the systemic release of insulin, growth hormone, prolactin, glucagon, progesterone, and placental lactogen.

This biology has direct implications on both digestive biology and the absorption of nutrients present in the intestine, as well as affecting energy balance by triggering satiety signals mediated by endocrine hormones.

The ability to modulate these hormones provides a therapeutic opportunity for decreasing caloric intake in metabolic disorders such as obesity or alternatively triggering appetite in muscle wasting, sarcopenia, and cachexia, as well as by shifting insulin sensitivity in the onset of diabetes. Arginine is an important signaling molecule for stimulating mTOR1 phosphorylation in a cell-specific manner. This regulates cellular protein turnover autophagy and integrates insulin-like growth signals to protein synthesis initiation across tissues.

This biology has been directly linked to biogenesis of lean tissue mass in skeletal muscle, metabolic shifts in disease states of obesity and insulin resistance, and aging.

It is also a central signaling pathway which can be hijacked for the proliferation of fast-growing cancer cells. There is evidence for Arginine increasing levels of protein synthesis in the small intestine under catabolic states such as viral infection and malnutrition, where amino acid levels are dramatically shifted from their normal post-absorptive states.

Additionally, demonstrated mTOR activation in the intestinal epithelial cells by Arginine provides a mechanism to repair intestinal epithelium by stimulating protein synthesis and cell proliferation.

Similar anabolic signaling has been observed in myocytes in response to rising plasma levels of Arginine, leading to increased whole body and skeletal muscle protein synthesis.

Arginine is an amino acid maintained at sufficient levels to support the anabolic effects of EAAs. Lysine, Methionine, Threonine, Tryptophan, Leucine, Isoleucine, and Valine have been shown unable to support increased protein synthesis and whole-body growth when added to a Arginine also up-regulates proteins and enzymes related to mitochondrial biogenesis and substrate oxidation, stimulating metabolism of fatty acid stores and reducing fat tissue mass.

Supplementation of dietary Arginine provides a therapeutic benefit in obese and pre-diabetic populations who suffer from insulin resistance due to their increased caloric intake. Likewise, the ability to stimulate mitochondrial biogenesis has direct implications in aging and the ability to regenerate functional proteins and healthy cells subject to oxidative stress. It is established that dietary deficiency of protein reduces the availability of most amino acids, including Arginine despite it not being considered essential.

Arginine supplementation has been demonstrated in animals to increase levels of Arginine, Proline, Ornithine, and other Arginine metabolites such as Polyamines in seminal fluid, corresponding with increased sperm counts and sperm motility. Changes in NO synthesis and polyamines via , likewise are seen during gestation when placental growth rate peaks, indicating a role for Arginine in fetal development during pregnancy.

In uterine fluids during early gestation, Arginine levels also decrease in response to expression of specific amino acid transporters at the embryo. Arginine supplementation to the diet of animals during early gestation has shown embryonic survival and increase in litter size, indicating a significant potential for delivering high levels of arginine during pregnancy. Arginine has an extensively studied effect on enhancing immune function, based on direct effects on NO production which can potentiate a phagocyte's killing ability , hormonal secretagogue activity, and stimulation of mTOR.

Proline catabolism by proline oxidase is known to have high levels of activity in the placentae and small intestine of mammals. This activity points to a crucial role for Arginine in gut and placentae immunity, both through generation of H 2 O 2 , which is cytotoxic to pathogenic bacteria, and synthesis of arginine. A clinical study in surgery, trauma, or sepsis patients examining Arginine enriched A separate clinical study of septic patients fed Arginine enriched Arginine is also a key substrate for the synthesis of collagen.

Oral supplementation of arginine enhances wound healing and lymphocyte immune response in healthy subjects. Arginine is an allosteric activator of N-acetylglutamate synthase, an enzyme which converts glutamate and acetyl-CoA into N-acetylglutamate in the mitochondria.

This pushes the hepatic urea cycle towards the active state, useful for ammonia detoxification. This means that dietary delivery of nutrients with low doses of arginine may be useful in the context of kidney disease, where patients struggle to clear urea from their circulation.

Elimination of arginine to limit uremia from the available nitrogen sources, while being able to maintain a limited protein intake to prevent tissue catabolism, is a novel strategy against a disruptive nutritional consequence of kidney disease. For this reason, delivery of high levels of Arginine to raise cellular levels of THB directly stimulates the biosynthesis of many neurotransmitters in the CNS capillary endothelial cells.

ArAAs serve as precursors for biosynthesis of monoamine neurotransmitters, including melatonin, dopamine, norepinephrine noradrenaline , and epinephrine adrenaline. Excessive arginine intake, stimulating production of high levels of NO in the blood can lead to oxidative injury and apoptosis of cells. Arginine excess or depletion affects global gene expression in mammalian hepatocytes. Many are relevant in luminal ER stress response.

LDLr, a regulator of cholesterol and steroid biosynthesis, was also modulated in response to arginine depletion. Consistent with Arginine affecting gene expression, dietary arginine supplementation up-regulates anti-oxidative genes and lowers expression of proinflammatory genes in the adipose and small intestinal tissues.

Lower arginine levels inhibit neurotransmitter biosynthesis, which has shown clinical efficacy in indications such as mania, parkinsons, and dyskenisia. Asparagine is a glucogenic nonessential amino acid, whose precursor is oxaloacetate OAA and which is synthesized via glutamine and aspartate by a transaminase enzyme. It is used for the function of some neoplastic cells such as lymphoblasts. Asparagine is typically located at the ends of alpha helices of proteins and provides important sites for N-linked glycosylation to add carbohydrate chains, which affects immune response to amino acid ingestion.

Acyrlamide is formed by heat-induced reactions between Asparagine and carbonyl groups of glucose and fructose in many plant-derived foods. Acrylamide is an oxidant that can be cytotoxic, cause gene mutations, and generally affect food quality. Compositions with low levels of asparagine are useful in making safer food products that may be subject to cooking or non-refrigerated storage conditions.

Aspartate is a glucogenic nonessential amino acid synthesized via the oxaloacetate OAA precursor by a transaminase enzyme. As part of the urea cycle, it can also be produced from ornithine and citrulline or arginine as the released fumarate is converted to malate and subsequently recycled to OAA. Aspartate provides a nitrogen atom in the synthesis of inosine, which is the precursor in purine biosynthesis.

Futon Plans Pdf Android Soft Close Drawer Slides Troubleshooting Android