With Other Amino Acids

The higher rigidity of the bicyclic scaffolds could favor the preferential formation of one of the two diastereoisomeric intermediates 71 and therefore explain the observed selectivity for compounds 73-75. 

Also in the case of the cyclic Schiff base 76, the bridged bicyclic nature of inter- 

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Further investigations, however, have shown that the above four-component peptide condensation is exceptionally efficient in terms of stereoselectivity70. A number of factors, including side reactions and insufficient solubility, influence this complex multistep reaction and these results cannot be reproduced with other amino acid combinations71. 

Lesions in conjunction with concentration studies can also be useful. Section of dorsal roots and degeneration of afferent fibres produces a reduction in glutamate and substance P which can then be associated with sensory inputs. Temporary reduction of the blood supply to the cord causes preferential destruction of interneurons and a greater loss of asparate and glycine, compared with other amino acids and so links... 

Similarly, the rate of inhibition of phosphoenzyme formation by diethylpyrocarbonate (DEPC) was much slower than the loss of ATPase activity [368], Even when the reaction approached completion with more than 90% inhibition of ATP hydrolysis, about 70% of the Ca -ATPase could still be phosphorylated by ATP (2.3nmoles of E P/mg protein). The remaining 30% of E P formation and the corresponding ATPase activity was not reactivated by hydroxylamine treatment, suggesting some side reaction with other amino acids, presumably lysine. When the reaction of the DEPC-modified ATPase with P-ATP was quenched by histidine buffer (pH 7.8) the P-phosphoenzyme was found to be exceptionally stable under the same conditions where the phosphoenzyme formed by the native ATPase underwent rapid hydrolysis [368]. The nearly normal phosphorylation of the DEPC-trea-ted enzyme by P-ATP implies that the ATP binding site is not affected by the modification, and the inhibition of ATPase activity is due to inhibition of the hydrolysis of the phosphoenzyme intermediate [368]. This is in contrast to an earlier report by Tenu et al. [367], that attributed the inhibition of ATPase activity by... 

Levodopa, a dopamine precursor, is the most effective agent for PD. Patients experience a 40% to 50% improvement in motor function. It is absorbed in the small intestine and peaks in the plasma in 30 to 120 minutes. A stomach with excess acid, food, or anticholinergic medications will delay gastric emptying time and decrease the amount of levodopa absorbed. Antacids decrease stomach acidity and improve levodopa absorption. Levodopa requires active transport by a large, neutral amino acid transporter protein from the small intestine into the plasma and from the plasma across the blood-brain barrier into the brain (Fig. 29-2). Levodopa competes with other amino acids, such as those contained in food, for this transport mechanism. Thus, in advanced disease, adjusting the timing of protein-rich meals in relationship to levodopa doses may be helpful. Levodopa also binds to iron supplements and administration of these should be spaced by at least 2 hours from the levodopa dose.1,8,16,25... 

With other amino acids, notably glycine and sarcosine, it is necessary to reflux the reactants 1-6 hours. 

These initial findings do not exclude other possible formaldehyde-induced reactions with tissue proteins. Notably, this first model system was not designed to detect the role of lysine residues. Lysine has a propensity to react with and form a variety of different types of cross-links with other amino acids in the presence of formaldehyde.1,3 417 Therefore, it is likely to also be important in reactions with formaldehyde. In fact, peptides with internal lysine residues were purposefully excluded from this initial study for technical reasons. To explore the importance of lysine residues in antigen retrieval, an alternative method was employed. 

The H64 distal ligand of wild-type myoglobin does not coordinate to the heme iron in either the reduced or the oxidized form of the native protein but stabilizes the coordination of a distally boimd water molecule of metMb. Replacement of H64 with other amino acid residues can, therefore, change the coordination environment of the heme iron in two ways. Such variants either may possess a distal residue that is able to coordinate to the heme iron or may possess a distal residue that is incapable of either coordinating to the iron or of forming a hydrogen bond with a coordinated water molecule. 

Some of the more interesting examples of nutrient - nonnutrient interactions include some of the compounds that are analogs of nutrients. Mattson et al (16) found that cholesterol absorption decreased when various plant sterols were added to the diets of rats. A number of plant amino acids are not ordinarily required by herbivores and are usually not incorporated into proteins. For example, the structure of 3,4-dihydroxyphenyl-alanlne (L-dopa) is similar to that of tyrosine. L-Dopa may play a role in favism (17), as well as having a number of other deleterious effects (18, 19, 20). Essential amino acids themselves can be deleterious if they are ingested in excessive quantities or if they are not in balance with other amino acids... 

The COs radical anion is a strong one-electron oxidant ( 7-1.7 V vs NHE [15]) that oxidizes appropriate electron donors via electron transfer mechanisms [103]. Detailed pulse radiolysis studies have shown that carbonate radicals can rapidly abstract electrons from aromatic amino acids (tyrosine and tryptophan). However, reactions of CO3 with S-containing methionine and cysteine are less efficient [104-106]. Hydrogen atom abstraction by carbonate radicals is generally very slow [103] and their reactivities with other amino acids are negligible [104-106]. 

Reference values of this approach are not different from those for other amino acid analyses. An example of a mass chromatogram, representing the plasma of a PKU patient, is shown in Fig. 2.1.1. When evaluating the results of MS/MS amino acid analyses, one has to reahze that the hquid chromatographic separation is by far less efficient that the AAA separation. For this reason, any amino acid may (partly) coelute with other amino acid(s), which potentially interferes with its mass spectromet-ric behavior. This effect is known as quenching. In order to overcome this as much as possible, stable-isotope-labeled internal standards (as many as possible) should be used. However, this matrix effect of ion suppression is the major pitfall in the MS/MS analysis of amino acids. Consequently, the MS/MS analysis of amino acids cannot be regarded as a reference method, similar to all other amino acid analytical methods. 

In individuals with PKU, a secondary, normally little-used pathway of phenylalanine metabolism comes into play. In this pathway phenylalanine undergoes transamination with pyruvate to yield phenylpyruvate (Fig. 18-25). Phenylalanine and phenylpyruvate accumulate in the blood and tissues and are excreted in the urine—hence the name phenylketonuria. Much of the phenylpyruvate, rather than being excreted as such, is either decarboxylated to phenylacetate or reduced to phenyllactate. Phenylacetate imparts a characteristic odor to the urine, which nurses have traditionally used to detect PKU in infants. The accumulation of phenylalanine or its metabolites in early life impairs normal development of the brain, causing severe mental retardation. This may be caused by excess phenylalanine competing with other amino acids for transport across the blood-brain barrier, resulting in a deficit of required metabolites. 

Crosslinked polymers of vinyl-substituted imidazolecarboxylic acids have been studied as chelating resins for heavy metal ions (78MI11101). For example, polymer (75) displays stabilities and capacities in the order Cu2+ > Ni2+ > Cd2+ > Zn2+ > Mg2+ which is similar to that observed with other amino acid chelating resins. The unusual feature of the polymer, however, is that exceptionally strong complexing abilities are maintained even in strongly acidic media. Polymer (75) also displayed potential utility for the removal of mercury(II) ions from aqueous media. 

In E. coli polypeptide chains are always initiated with the amino acid N-formylmethionine. Some bacteria can apparently live without the ability to formylate methionyl-tRNA,290 but most eubacteria as well as mitochondria and chloroplasts use formyl-methionine for initiation. In a few cases, both among bacteria and eukaryotes, initiation can sometimes occur with other amino acids 291 The first step is the alignment of the proper initiation codon correctly on... 

Refolding is generally found to proceed by a series of exponential phases. Many of these exponentials are a consequence of cis-trans isomerization about peptidyl-prolyl bonds.14,15 The equilibrium constant for the normal peptide bond in proteins favors the trans conformation by a factor of 103-104 or so. The peptidyl-prolyl bond is an exception that has some 2-20% of cis isomer in model peptides (see Chapter 1, Figure 1.3). Further, it is often found as the cis isomer in native structures. (Replacement of ds-prolines with other amino acids by protein engineering can retain the cis stereochemistry.16) The interconversion of cis to trans in solution is quite slow, having half-lives of 10-100 s at room temperature and neutral pH. This has two important consequences. First, a protein that has several... 

In the chain from soils to plants to humans, inorganic sulfur, or more accurately, the sulfate ion (SO42-), is taken up by plants and converted within the plant to organic compounds (the sulfur amino acids). These amino acids combine with other amino acids to make up plant protein. When the plant is eaten by a human or by livestock animals, die protein is broken down and die amino acids are absorbed from the digestive tract and recombined 111 the proteins of the animal body. The most important feature of sulfur in die food chain is that plants use inorganic sulfur compounds to make sulfur amino acids, whereas animals and humans use the sulfur amino acids for their own processes and excrete inorganic sulfur compounds resulting from the metabolism of the sulfur amino acids. 

A number of residues may be replaced with other amino acids without apparent change in enzymic activity. These replacements include nor-leucine for methionine at positions 26 and 32 87), phenylalanine for tyrosine 27 92), and glycine for histidine 46 85). As mentioned above, deletion of histidine 8 is without deleterious effect. The two remaining residues of histidine at positions 121 and 124 may also be ruled out as components of the active site since the former is, stereoehemically, far on the other side of the molecule and the latter is replaced by leucine in nuclease from the Foggi strain of Staphylococcus aureus. 

V Fabian, M Pinter-Szakacs, I Molnar-Perl. Gas chromatography of tryptophan together with other amino acids in hydrochloric acid hydrolysates. J Chromatogr 520 193-199, 1990. 

Fig. 1. a-Oxidation of amino acids. Hydroxyl radical (or other reactive radical) abstracts hydrogen atom from the a-carbon. The C-centered free radical formed may react with other amino acid residues or dimerize in the absence of oxygen, which leads to protein aggregation. In die presence of oxygen the carbon-centered radical forms peroxyl radical. Reduction of peroxyl radical leads to protein hydroperoxide. Decomposition of hydroperoxide leads to formation of carbonyl compounds via either oxidative deamination or oxidative decarboxylation. Oxidation of the new carbonyl group forms a carboxyl group. 

In this reaction the H and OH highlighted in bold have been removed to form a molecule of water. The carbonyl of the amino acid on the left formed a bond with the nitrogen atom in the amino acid on the right. The amide functional group was formed in this dehydration synthesis reaction. Notice the ends of the newly formed dipeptide. There exists another amine group and carboxylic acid group at the ends of this chain to join with other amino acids and lengthen the chain. 

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