[Effects of several antituberculous drugs on amino acid metabolism. I. Amino acid metabolism of rats administered large doses of isonicotinic acid hydrazide (INH)].
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Amino acid metabolism may be adversely affected by vitamin B-6 deficiency. The effects of a maternal deficiency of vitamin B-6 on concentrations of amino acids in substantia nigra (SN), caudate nucleus/putamen (C/P) and cortex (CORT) in progeny were studied. Female albino rats were fed diets containing either 0.6 (deficient) or 7.0 (control) mg pyridoxine x HCl (PN x HCl) per kilogram diet ad libitum throughout growth, gestation and lactation. Paralleling a significant decrease in body weight, pups in the deficient groups began to show gross neurological symptoms of the deficiency at approximately 11 days of age. Analysis of brain regions at 15 days of age showed that the deficiency resulted in decreased concentrations of alanine and serine in SN, C/P and CORT. Often these changes were more pronounced in one or two of the regions analyzed. At 1 and 3 hours after an intraperitoneal injection of 100 mg PN x HCl per kilogram body weight into deficient pups, concentrations of cystathionine, leucine, isoleucine, valine, alanine and serine in brain regions remained similar to preinjection values. However, within 3 hours postinjection, glycine concentrations had decreased and were similar to control levels in SN and C/P.
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Tobacco transformants that express an antisense RBCS construct were used to investigate the consequences of a lesion in photosynthetic carbon metabolism for nitrogen metabolism and secondary metabolism. The results show that an inhibition of photosynthesis and decrease in sugar levels leads to a general inhibition of nitrogen metabolism, and dramatic changes in the levels of secondary metabolites. The response was particularly clear in plants that received excess nitrogen. In these conditions, a decrease of Rubisco activity led to an inhibition of nitrate reductase activity, accumulation of nitrate, a decrease of amino acid levels that was larger than the decrease of sugars, and a large decrease of chlorogenic acid and of nicotine, which are the major carbon- and nitrogen-rich secondary metabolites in tobacco leaves, respectively. Similar changes were seen when nitrogen-replete wild-type tobacco was grown in low light. The inhibition of nitrogen metabolism was partly masked when wild-type plants and antisense RBCS transformants were compared in marginal or in limiting nitrogen, because the lower growth rate of the transformants alleviated the nitrogen deficiency, leading to an increase of amino acids. In these conditions, chlorogenic acid always decreased but the decrease of nicotine was ameliorated or reversed. When the changes in internal pools are compared across all the genotypes and growth conditions, two conclusions emerge. First, decreased levels of primary metabolites lead to a dramatic decrease in the levels of secondary metabolites. Second, changes of the amino acid : sugar ratio are accompanied by changes of the nicotine:chlorogenic acid ratio.
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Sulfur amino acid metabolism in Saccharomyces cerevisiae is regulated by the level of intracellular S-adenosylmethionine (AdoMet). Two cis-acting elements have been previously identified within the 5' upstream regions of the structural genes of the sulfur network. The first contains the CACGTG motif and is the target of the transcription activation complex Cbflp-Met4p-Met28p. We report here the identification of two new factors, Met31p and Met32p, that recognize the second cis-acting element. Met31p was isolated through the use of the one-hybrid method, while Met32p was identified during the analysis of the yeast methionine transport system. Met31p and Met32p are highly related zinc finger-containing proteins. Both LexA-Met31p and LexA-Met32p fusion proteins activate the transcription of a LexAop-containing promoter in a Met4p-dependent manner. Northern blot analyses of cells that do not express either Met31p and/or Met32p suggest that the function of the two proteins during the transcriptional regulation of the sulfur network varies from one gene to the other. While the expression of both the MET3 and MET14 genes was shown to strictly depend upon the presence of either Met31p or Met32p, the transcription of the MET25 gene is constitutive in cells lacking both Met31p and Met32p. These results therefore emphasise the diversity of the mechanisms allowing regulation of the expression of the methionine biosynthetic genes.
Fetal amino acid nutrition and metabolism have been studied primarily in pregnant sheep. The umbilical uptake of amino acids changes during gestation, but at both mid- and late gestation the total supply exceeds that required for growth. Weight-specific protein synthetic rate decreases with increasing gestational age, and these changes are proportional to the changes in metabolic rate. The use of multiple tracer methodology coupled with measurement of net tracer fluxes into and out of fetal and placental tissues can be used to delineate amino acid metabolism in considerable detail. Such studies demonstrate that even essential amino acids can be oxidized extensively by the fetus. The oxidation rate of leucine exceeds its rate of accretion in tissue proteins. Glycine metabolism is unique in several ways; there is a large umbilical uptake of glycine without a measurable uterine uptake. In late gestation there is no significant umbilical uptake of serine, although there is a significant uterine uptake, suggesting net uteroplacental utilization. Glycine is oxidized within the fetal liver and used for serum production. The interorgan exchange of amino acids between the fetal liver and placenta is clearly of major importance for serine and glycine metabolism and is likely to be of major importance for most nonessential amino acids.
Amino acids are major constituents of biological material. Chemically they are extremely stable and combine a relatively simple molecular structure with a wide range of properties and functions. In general, amino acid metabolism in helminths has been relatively neglected and the information available is often uneven and of uncertain quality. However, the search for new target sites for anthelmintic development has led to a renewed interest in this area. The amino acid composition of helminths is similar to that of other invertebrates and no unique amino acids have been reported. With the possible addition of tyrosine, helminths seem to require the same 10 essential amino acids as mammals and, where studied in detail, the pathways of amino acid synthesis in helminths are similar to those of mammals. Although amino acids are not a significant energy source in parasites, helminths are able to catabolize amino acids by pathways which, again, appear identical to those found in mammals. Helminths have also been shown to carry out a number of oxidative reactions associated with amino acid metabolism, including cysteine dioxygenase, proline hydroxylase and tryptophan hydroxylase. There are, however, differences in detail between the pathways of amino acid metabolism in helminths and mammals, particularly in the metabolism of the sulphur amino acids and arginine and proline. These differences may be exploitable in anthelmintic design and proline analogues and proline biosynthesis inhibitors show some potential as fasciolicides (Sheers et al., 1982). Differences in metabolism between parasites and their hosts may be the result of parasitic adaptation or they may merely reflect general features of the invertebrate phyla as a whole. Thus a comparison of amino acid metabolism in parasitic helminths with that of their free-living relatives may give some insight into the biochemical basis of parasitism.
Although fatigue during prolonged exercise has traditionally been associated with peripheral factors relating to muscle metabolism, such as the depletion of muscle glycogen, more recent research has generated a renewed interest in amino acid metabolism per se and in the role of amino acids as precursors of brain neurotransmitter function. The concept of a 'central fatigue hypothesis' has done much to stimulate scientists to explore the functional role of the brain and CNS in the aetiology of the fatigue process. The concept has also generated a number of testable hypotheses by which it is possible to examine how the 'central' component of fatigue may act. The present review has attempted to bring together the current research in this area. There is good reason to believe that nutritional intervention may play an important role in relation to fatigue residing within the brain and CNS. Although an exciting possibility exists that nutritional manipulation may affect brain neurochemistry and ultimately sports performance, the experimental evidence to support this claim is, as yet, equivocal. A greater understanding of amino acid metabolism and, in particular, amino acid transport, will greatly improve future experimental designs used to test the efficacy of nutritional manipulation of amino acids and their effect on the central component of the fatigue process.
To evaluate changes in the liver ability to metabolize amino acids during intake of different proteins, the content of free amino acids was measured in the blood of the portal and liver veins of rats fed krill protein and casein. After 48 h of fasting the animals were given a suspension of krill protein and casein at a rate of 540 mg protein per 100 g bw. After 0.5, 1, 3 and 6 h the content of free amino acids was measured in the blood of the portal and liver veins by ion exchange chromatography with the use of an automatic amino acid analyzer. Administration of krill protein brought about a high enough (63%) absorption of amino acids by the liver during the 6-hour experiment. The degree of casein absorption was 31%. As compared to casein, intake of krill protein led to an earlier saturation of the body with amino acids having branched chains (P less than 0.05). The enzymatic systems of amino acid metabolism responded to the supply of the proteins under study in the same manner, however the rate of adaptation was different, amounting to 0.5 h for krill protein and to 3 h for casein. It is evident that the enzymatic systems involved in amino acid metabolism respond to the intake of krill protein to a larger extent than enzymes involved in metabolism of casein amino acids.
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The amino acid composition of the plasma and serum of Salyut-6 crewmembers who performed flights of different duration was investigated. The parameter was found to vary depending on the flight time and use of different countermeasures. The 75- and 185-day cosmonauts who did not exercise in a full measure showed a decrease in the amino acid pool typical of emergency situations. The 96-, 140- and 175-day crewmembers who exercised as prescribed exhibited the lack of changes in the total content of amino acids and variations in the content of individual amino acids. The results of the study of the amino acid composition can be applied to the evaluation of inflight countermeasures, e.g. exercises, and to the development of rehabilitation measures postflight.