Amino acid de novo

Humans have a limited capacity to synthesize amino acids de novo, but extensive interconversions can occur. Those amino acids which cannot be formed within the body and must be supplied by the diet are called essential . Members of this group, which includes the branched chain amino acids leucine and valine, and also methionine and phenylalanine, are all dietary requirements. Such essential amino acids may be chemically converted, mainly in the liver, into the non-essential amino acids. The term non-essential does not equate with not biochemically important but simply means they are not strict dietary components. 

An interesting possibihty, never investigated, is that the bear possesses the ability to synthesise both dispensable and non-dispensable amino acids de novo, from the ammonia released by the microorganisms. As far as is known, no mammal possesses the enzymes necessary to synthesise the indispensable amino acids. It would be interesting if another adaptation to such a long hibernation is development of enzymes necessary to synthesise indispensable amino acids. This possibility is supported by the... 

The nonessential amino acids are synthesized by quite simple reactions, whereas the pathways for the formation of the essential amino acids are quite complex. For example, the nonessential amino acids alanine and aspartate are synthesized in a single step from pyruvate and oxaloacetate, respectively. In contrast, the pathways for the essential amino acids require from 5 to 16 steps (Figure 24.8). The sole exception to this pattern is arginine, inasmuch as the synthesis of this nonessential amino acid de novo requires 10 steps. Typically, though, it is made in only 3 steps from ornithine as part of the urea cycle. Tyrosine, classified as a nonessential amino acid because it can be synthesized in 1 step from phenylalanine, requires 10 steps to be synthesized from scratch and is essential if phenylalanine is not abundant. We begin with the biosynthesis of nonessential amino acids. 

Plants synthesize all 20 common amino acids de novo. Glyphosate, a weed killer sold under the trade name Roundup, is an analog of phosphoenolpyruvate that specifically inhibits 3-enolpyruvylshikimate 5-phosphate synthase, a key enzyme of the pathway for chorismate biosynthesis. This compound is a very effective plant herbicide, but has virtually no effect on mammals. Why ... 

Other approaches to de novo four-helix bundle proteins have emphasized nonrepetitive designs. One such example is the four-helix bundle protein Felix (53), a 79-residue protein which uses 19 of the 20 naturally occurring amino acids ... 

Carnivores rely on a protein-rich diet and produce new biomass primarily from dietary amino acids, although the enzymes required for de novo amino acid synthesis are present (Garmes et al., 1998). Bone collagen, muscle (meat) and apatite were analyzed for a set of modern southern African herbivores and carnivores (Lee-Thorp et al., 1989). The isotopic analyses showed i C enrichment in bone collagen, apatite and muscle, and depletion in lipids. Difference in values between herbivores and carnivores indicates a trophic effect, which for carbon in bone collagen is 2.5-3%o (Fig. 2). 

Methodologies for the de novo design and synthesis of polypeptides were recently developed. The preparation of periodic polypeptides, polypeptides containing artificial amino acids, polypeptides exhibiting rodlike structures, and hybrids of natural and artificial polypeptide segments was recently described [33],... 

In 1975, SAR studies involving actinonin investigated an analogue in which the orientation of the Pl -P2 amide bond was reversed (13), but the compound was found to lack antibacterial activity. Since then, however, descriptions of some /i-aminohydroxamic acids and /i-amino-A-formyl-A-hydroxylamines as PDF inhibitors have appeared in the patent literature. Patent applications from Senju [97] and De Novo [98] pharmaceuticals cover Pl -P2 amides (14), ureas (15, 16) and sulfonamides (17). 

Soil microorganisms produce many compounds that are potentially toxic to higher plants. Examples include members of the following antibiotics (1-6), fatty and phenolic acids (7-12), amino compounds (13-15), and trichothecenes (16, 17). "Soil sickness" and "replant problems" have been reported where certain crops or their residues interfere with establishment of a subsequent crop (18, 19). Toxins resulting from microbial activity sometimes are involved, but it is often unclear whether these are synthesized de novo in microbial metabolism or are breakdown products of the litter itself (20). 

Coleoptera comprise the largest order of insects and accordingly pheromone structures and biochemical pathways are diverse [98, 99]. Beetle pheromone biosynthesis involves fatty acid, amino acid, or isoprenoid types of pathways. In some cases dietary host compounds can be converted to pheromones, but it is becoming apparent that most beetle pheromones are synthesized de novo. 

In summary, the de novo isolation of the cDNAs encoding enzymes of alkaloid biosynthesis is still achieved by using a variety of classical techniques, such as protein purification followed by partial amino acid sequence determination, and by newer techniques such as proteomics coupled to functional heterologous expression. The current status of cloned cDNAs specifically related to isoquinoline alkaloid biosynthesis is schematically presented in Figure 10.8. New additions to this list will certainly be made in the future as a result of a combination of approaches both new and old. 

Here we encountered a typical situation in the de novo sequencing—there is a part of the sequence that is not covered by any ion series. Not all bonds between amino acids are of equal strength, and some of them might be particularly resistant to collisions, which in turn results in the missing mass-shifts (and missing residues). 

Arches with the same conformation tend to have similar amino acid sequence patterns for key apolar, polar, or glycine residues (Hennetin et al., 2006). At the same time, the sequence patterns of the various kinds of arches differ in a characteristic manner (Fig. 12) and this information may be helpful for the prediction, modeling, and de novo design of /2-solenoids. 

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