History of parenteral nutrition in pediatrics with emphasis on amino acids

Central venous total parenteral nutrition (TPN) has proved to be a valuable and often life-saving measure in selected newborn infants with surgically repairable, major anomalies of the gastrointestinal tract and infants with chronic intractable diarrhea. However, in infants of low--and especially very low--birth weight, the TPN regimen that was so successful in older infants was frequently associated with severe risks of hyperglycemia. An alternative approach that has proved to be the most satisfactory relies on the fact that the energy expenditure of a premature infant, nursing in a thermally neutral environment, rarely exceeds 50 kcal/kg, a level that can be safely and effectively maintained. With respect to the development of parenteral amino acid solutions, three generations of such mixtures can now be identified. The first of these was represented by the protein hydrolysates. With the advent of technology for the production of pure L-amino acids, a second generation of crystalline mixtures was developed. Evaluation of these revealed that extrapolation from data on oral nutrition was often unsatisfactory for the adequate formulation of such mixtures. The direct study of the parenterally nourished patient led to the third generation of special purpose amino acid solutions such as those targeted for patients with renal failure, liver failure, or trauma or for the promotion of anabolism. It seems likely that development of other solutions will follow the trend of relying on accurate definition of a given metabolic disorder and the perfection of a specific solution to correct it.     

Amino acid and codon usage profiles: adaptive changes in the frequency of amino acids and codons

In the work presented, the changes in codon and amino acid contents have been studied as a function of environmental conditions by comparing pairs of homologs in a group of extremophilic/non-extremophilic genomes. Our results obtained based on such analysis highlights a number of notable observations: (i) the overall preference of amino acid usages in the proteins of a given organism is significantly affected by major environmental factors. The changes in amino acid preferences (amino acid usage profiles) in an extremophile compared to its non-extremophile relative recurs in the organisms of similar extreme habitats. (ii) On the other hand, changes in codon usage preferences in these extremophilic/non-extremophilic pairs, lack such persistency not only in different genome-pairs but also in the individual genes of a specific pair. (iii) We have noted a correlation between cellular function and codon usage profiles of the genes in the studied pairs. (iv) Based on this correlation, we could obtain a decent prediction of cellular functions solely based on codon usage profile data. (v) Comparisons made between two sets of randomly generated genomes suggest that different patterns of codon usage changes in genes of different functional categories result in a partial resistance towards the changes in the concentration of a given amino acid. This buffering capacity might explain the observed differences in codon usage trends in genes of different functions. In the end, we suggest codon usage and amino acid profiles as powerful tools that can be utilized to improve function predictions and genome-environment mappings.     

Multiple-impeller systems with a special emphasis on bioreactors: a critical review

The multiple-impeller agitated systems are compared with single-impeller agitated systems with a special focus on its applications for bioreactors. Correlations reported in the literature for gas phase hold-up, mass transfer coefficient and power consumption under gassed and ungassed conditions are compared and recommendations have been made regarding their suitability for design and scale-up of bioreactors. The multiple-impeller systems are found to be superior as compared to single-impeller systems in all the above mentioned aspects, except liquid mixing. For all kinds of reactors where the sole purpose is mass transfer, multiple-impeller systems are advantageous and there would be large savings on an industrial scale, especially for the bioreactors where the reaction periods are long and the power consumption cost could be a significant component to the overall production costs.     

Amino acid requirements of the mosquito Culex pipiens: asparagine essential

When any of the ten “rat essential” amino acids was omitted singly from a fully-defined synthetic dietary medium, newly-hatched Culex pipiens larvae were unable to develop to the second instar. With proline omitted, development was greatly retarded and survival to the adult stage reduced. Without aspargine (but not aspartic acid) growth and development ceased in most individuals before larval-pupal ecdysis, and no adults were obtained. These twelve amino acids are considered nutritionally essential for this mosquito. With glycine omitted singly, development was markedly retarded, but survival to the adult stage was not affected; thus this amino acid is required for good growth, but these experiments do not demonstrate it as essential. Single omission of alanine, aspartic acid, cysteine, glutamic acid or amide, serine or tyrosine had virtually no effect on development and they are therefore considered nutritionally non-essential. With diets containing the twelve culex-essential amino acids only, very little development occurred, but augmentation with either glycine or serine allowed growth and development almost as good as with the complete amino acid mixture. Augmentation of the essential twelve with alanine, cysteine, glutamic acid/amide, or tyrosine singly failed to improve development. The requirement for dietary asparagine shown by these studies appears to be unique among insects so far studied. In particular, another mosquito, Aedes aegypti, has no such requirement.     

Amino acid transport in a polyaromatic amino acid auxotroph of Saccharomyces cerevisiae

The initiation of growth of a polyaromatic auxotrophic mutant of Saccharomyces cerevisiae was inhibited by several amino acids, whereas growth of the parent prototroph was unaffected. A comparative investigation of amino acid transport in the two strains employing (14)C-labeled amino acids revealed that the transport of amino acids in S. cerevisiae was mediated by a general transport system responsible for the uptake of all neutral as well as basic amino acids. Both auxotrophic and prototrophic strains exhibited stereospecificity for l-amino acids and a K(m) ranging from 1.5 x 10(-5) to 5.0 x 10(-5) M. Optimal transport activity occurred at pH 5.7. Cycloheximide had no effect on amino acid uptake, indicating that protein synthesis was not a direct requirement for amino acid transport. Regulation of amino acid transport was subject to the concentration of amino acids in the free amino acid pool. Amino acid inhibition of the uptake of the aromatic amino acids by the aromatic auxotroph did not correlate directly with the effect of amino acids on the initiation of growth of the auxotroph but provides a partial explanation of this effect.     

Effect of L-malic and citric acids metabolism on the essential amino acid requirements for Oenococcus oeni growth

AIMS: The purpose of this work was to study the effect of L-malic and/or citric acids on Oenococcus oeni m growth in deficient nutritional conditions, and their roles as possible biosynthetic precursors of the essential amino acids. METHODS AND RESULTS: Bacterial cultures were performed in synthetic media. Bacterial growth rate was reduced or annulled when one amino acid was omitted from basal medium, especially for members of aspartate family, except lysine. The organic acids increased or restored the growth rates to the respective reference values. In each medium deficient in one essential amino acid, the L-malic acid utilization was accompanied by an increase of L-lactic acid concentration and accounted for approximately 100%l-malic acid consumed. D-lactic acid formation from glucose decreased in the medium without cysteine. Except for tyrosine, the recovery of glucose-citrate as D-lactic acid was lower than in the complete medium when asparagine, isoleucine or cysteine were excluded. The ethanol and acetate production was not modified. CONCLUSIONS: L-malic and citric acids favoured Oenococcus oeni m growth in nutritional stress conditions. Specifically citric acid was involved in the biosynthesis of the aspartate-derived essential amino acids and glucose in the cysteine biosynthesis. SIGNIFICANCE AND IMPACT OF THE STUDY: Such beneficial effect of l-malic and citric acids on amino acids requirements of Oenococcus oeni m have great significance considering the low amino acids concentration in wine.     

Amino acids regulate retrieval of the yeast general amino acid permease from the vacuolar targeting pathway

Intracellular sorting of the general amino acid permease (Gap1p) in Saccharomyces cerevisiae depends on availability of amino acids such that at low amino acid concentrations Gap1p is sorted to the plasma membrane, whereas at high concentrations Gap1p is sorted to the vacuole. In a genome-wide screen for mutations that affect Gap1p sorting we identified deletions in a subset of components of the ESCRT (endosomal sorting complex required for transport) complex, which is required for formation of the multivesicular endosome (MVE). Gap1p-GFP is delivered to the vacuolar interior by the MVE pathway in wild-type cells, but when formation of the MVE is blocked by mutation, Gap1p-GFP efficiently cycles from this compartment to the plasma membrane, resulting in unusually high permease activity at the cell surface. Importantly, cycling of Gap1p-GFP to the plasma membrane is blocked by high amino acid concentrations, defining recycling from the endosome as a major step in Gap1p trafficking under physiological control. Mutations in LST4 and LST7 genes, previously identified for their role in Gap1p sorting, similarly block MVE to plasma membrane trafficking of Gap1p. However, mutations in other recycling complexes such as the retromer had no significant effect on the intracellular sorting of Gap1p, suggesting that Gap1p follows a genetically distinct pathway for recycling. We previously found that Gap1p sorting from the Golgi to the endosome requires ubiquitination of Gap1p by an Rsp5p ubiquitin ligase complex, but amino acid abundance does not appear to significantly alter the accumulation of polyubiquitinated Gap1p. Thus the role of ubiquitination appears to be a signal for delivery of Gap1p to the MVE, whereas amino acid abundance appears to control the cycling of Gap1p from the MVE to the plasma membrane.