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1.
Summary. Since peptide quinones possess great clinical potential in targeted chemotherapy, several series of novel N-quinonyl amino
acids have been synthesized and their first products of reduction were studied by EPR spectroscopy. EPR spectra of the corresponding
radical adducts were identified by computer simulation. The dependence between the splitting constants and the chemical structure
of the N-quinonyl amino acids anion radicals was examined.
Received January 4, 2000; Accepted March 14, 2000 相似文献
2.
Protein-bound advanced glycation endproducts (AGEs) as bioactive amino acid derivatives in foods 总被引:2,自引:0,他引:2
Henle T 《Amino acids》2005,29(4):313-322
Summary. The Maillard reaction or nonenzymatic browning is of outstanding importance for the formation of flavour and colour of heated
foods. Corresponding reactions, also referred to as “glycation”, are known from biological systems, where the formation of
advanced glycation endproducts (AGEs) shall play an important pathophysiological role in diabetes and uremia. In this review,
pathways leading to the formation of individual protein-bound lysine and arginine derivatives in foods are described and nutritional
consequences resulting from this posttranslational modifications of food proteins are discussed. 相似文献
3.
Summary. Hepatocytes were cultured for 3 days as spheroids (aggregates) or as monolayers in basal medium and in sulfur amino acid-supplemented
media. Cultured hepatocytes had low levels of cysteine dioxygenase (CDO) activity and normal levels of γ-glutamylcysteine
synthetase (GCS) and cysteinesulfinate decarboxylase (CSDC) activities compared to freshly isolated cells. CDO activity increased
and GCS activity decreased in a dose-response manner in cells cultured in either methionine- or cysteine-supplemented media.
CSDC activity was not significantly affected by methionine supplementation. Changes in CDO and GCS were associated with changes
in cysteine catabolism to taurine plus sulfate and in synthesis of glutathione, respectively. These responses are similar
to those observed in liver of intact rats fed diets supplemented with sulfur amino acids. A near-maximal response of CDO or
GCS activity was observed when the medium contained 1.0 mmol/L of methionine plus cyst(e)ine. Changes in CDO and GCS activities
did not appear to be mediated by changes in the intracellular glutathione concentration. Cultured hepatocytes offer a useful
model for further studies of cysteine metabolism and its regulation in response to sulfur amino acid availability.
Received June 2, 1999/Accepted September 16, 1999 相似文献
4.
Summary. Due to the obvious advantages of long-acting peptide and protein drugs, strategies to prolong plasma half life time of such
compounds are highly on demand. Short plasma half life times are commonly due to fast renal clearance as well as to enzymatic
degradation occurring during systemic circulation. Modifications of the peptide/protein can lead to prolonged plasma half
life times. By shortening the overall amino acid amount of somatostatin and replacing l-analogue amino acids with d-amino acids, plasma half life time of the derivate octreotide was 1.5 hours in comparison to only few minutes of somatostatin.
A PEG2,40 K conjugate of INF-α-2b exhibited a 330-fold prolonged plasma half life time compared to the native protein. It was the aim
of this review to provide an overview of possible strategies to prolong plasma half life time such as modification of N- and
C-terminus or PEGylation as well as methods to evaluate the effectiveness of drug modifications. Furthermore, fundamental
data about most important proteolytic enzymes of human blood, liver and kidney as well as their cleavage specificity and inhibitors
for them are provided in order to predict enzymatic cleavage of peptide and protein drugs during systemic circulation. 相似文献
5.
Summary. The influence of nitric oxide synthase (NOS) activity on the KCl-evoked amino acid concentrations was investigated by in vivo microdialysis in the striatum in a rat model of excitotoxic lesion. Basal microdialysate levels of amino acids decreased
during the quinolinic acid-induced neurodegeneration process, except for glutamine that increased initially and returned to
control values 30 days after quinolinic acid exposure. KCl-evoked increase of extracellular amino acid concentration was reduced
due to NOS activity in the striatum of both controls and lesioned animals, except for 120 days after quinolinic acid injection.
These changes of amino acid concentrations in microdialysates correlated with the known biochemistry of the consecutive domineered
cell types during the lesion process as revealed by histochemistry for NOS, NADPH-diaphorase, GFAP and isolectin B4. The present
data provide direct evidence that NOS activity can modulate extracellular amino acid concentrations in the striatum not only
under physiological conditions, but also during a pharmacologically induced lesion process and, thus, suggests that nitric
oxide affects neurodegeneration via this pathway.
Received October 20, 1999; Accepted February 25, 2000 相似文献
6.
Garcia RF Gazola VA Barrena HC Hartmann EM Berti J Toyama MH Boschero AC Carneiro EM Manso FC Bazotte RB 《Amino acids》2007,33(1):151-155
Summary. Our purpose was to determine the blood amino acid concentration during insulin induced hypoglycemia (IIH) and examine if the
administration of alanine or glutamine could help glycemia recovery in fasted rats. IIH was obtained by an intraperitoneal
injection of regular insulin (1.0 U/kg). The blood levels of the majority of amino acids, including alanine and glutamine
were decreased (P < 0.05) during IIH and this change correlates well with the duration than the intensity of hypoglycemia. On the other hand,
the oral and intraperitoneal administration of alanine (100 mg/kg) or glutamine (100 mg/kg) accelerates glucose recovery.
This effect was partly at least consequence of the increased capacity of the livers from IIH group to produce glucose from
alanine and glutamine. It was concluded that the blood amino acids availability during IIH, particularly alanine and glutamine,
play a pivotal role in recovery from hypoglycemia. 相似文献
7.
Summary. The proton coupled amino acid transporter PAT1 expressed in intestine, brain, and other organs accepts L- and D-proline, glycine,
and L-alanine but also pharmaceutically active amino acid derivatives such as 3-amino-1-propanesulfonic acid, L-azetidine-2-carboxylic
acid, and cis-4-hydroxy-D-proline as substrates. We systematically analyzed the structural requirements for PAT1 substrates
by testing 87 amino acids, proline homologs, indoles, and derivatives. Affinity data and effects on membrane potential were
determined using Caco-2 cells. For aliphatic amino acids, a blocked carboxyl group, the distance between amino and carboxyl
group, and the position of the hydroxyl group are affinity limiting factors. Methylation of the amino group enhances substrate
affinity. Hetero atoms in the proline template are well tolerated. Aromatic α-amino acids display low affinity. PAT1 interacts
strongly with heterocyclic aromatic acids containing an indole scaffold. The structural requirements of PAT1 substrates elucidated
in this study will be useful for the development of prodrugs. 相似文献
8.
Summary. The stability of felinine, an amino acid present in feline urine, was investigated. Synthetic felinine was unstable in the
urine of a selection of mammals. Felinine was found to stable in feline urine in which urea had been degraded. Synthetic felinine
was found to react specifically with urea and did not react with urea analogues such as biuret or thiourea or other nucleophilic
compounds such as ammonia which is more nucleophilic or acetamide and water which are less nucleophilic than urea. The reaction
of urea and felinine was independent of pH over the range of 3–10. Urea did not react with N-acetyl-felinine suggesting a felinine N-terminal interaction with urea. Mass spectral analysis of the reaction products showed
the presence of carbamylated felinine and fragmentation ions derived from carbamyl-felinine. The physiological relevance of
felinine carbamylation is yet to be determined. 相似文献
9.
Summary. In this study, we found that two amino acids reacted with 2,5-hexanedione to form new reaction products in vitro, respectively.
In the reaction of beta-alanine and 2,5-hexanedione, a reaction product was obtained and analyses of obtained results showed
it was 3-(2,5-dimethyl-1H-pyrrol-1-yl)propanoic acid; in the reaction of glycine and 2,5-hexanedione, a reaction product was also obtained and analyses
showed it was (2,5-dimethyl-1H-pyrrol-1-yl)acetic acid. Two reaction products were found to be oxidized easily; in addition, the latter was more easily
to be oxidized than the former in the air. Our discoveries demonstrated that reactions between amino acids and 2,5-hexanedione
could exist possibly in vitro. At present, it is clear that 2,5-hexanedione causes either axon atrophy or swelling, but the
underlying molecular mechanism is still unclear. Since both beta-alanine and glycine are considered as neurotransmitter in
the central nervous system, the reaction products remain to be identified in vivo. 相似文献
10.
Summary. Amino acids analysis in single wheat embryonic protoplast was performed using capillary electrophoresis equipped with laser-induced
fluorescence (CE-LIF), combination with tissue culture technique. Reagent fluorescein isothiocyanate (FITC) was introduced
into living protoplasts by electroporation for intracellular derivatization. A special osmotic buffer (0.6 mol/L mannitol,
5 mmol/L CaCl2) was used to keep the osmotic balance of embryonic protoplasts during the protoplasts derivatization. After completion of
the derivatization reaction in the protoplasts, a single protoplast was drawn into the capillary tip by electroosmotic flow.
Then a 0.1 M NaOH lysing solution was injected by diffusion. The derivatized amino acids were separated by capillary electrophoresis
and detected by laser-induced fluorescence detection after the protoplast was lysed Nine amino acids were quantitatively and
qualitatively determined and compared in lysate and single protoplast of wheat embryonic cells respectively, with mean concentrations
of amino acids ranging from 2.68×10−5 mol/L to 18.18×10−5 mol/L in single protoplast. 相似文献
11.
Summary. A technique is described for the enantiomeric determination of L- and D-amino acids. It works on the principle that the separation
efficiency of high-performance liquid chromatography is coupled with the specificity of enzymes and the sensitivity of electrochemical
detection. After separation on a lithium cation-exchange column the amino acids are converted into keto acids and hydrogen
peroxide under catalyzation of L- or D-amino acid oxidase. Hydrogen peroxide is detected amperometrically. The method has
been tested by the analysis of beer, port, sherry, wine and fruit juice.
A main emphasis was put onto the determination of D-alanine which can serve as an indicator for bacterial contamination. It
is shown that a coupling of HPLC with enzyme reactors is a suitable technique for the rapid detection of this marker.
Received April 14, 1999, Accepted September 15, 1999 相似文献
12.
Summary. The concentrations of free amino acids in plasma change coordinately and their profiles show distinctive features in various
physiological conditions; however, their behavior can not always be explained by the conventional flow-based metabolic pathway
network. In this study, we have revealed the interrelatedness of the plasma amino acids and inferred their network structure
with threshold-test analysis and multilevel-digraph analysis methods using the plasma samples of rats which are fed diet deficient
in single essential amino acid.
In the inferred network, we could draw some interesting interrelations between plasma amino acids as follows: 1) Lysine is
located at the top control level and has effects on almost all of the other plasma amino acids. 2) Threonine plays a role
in a hub in the network, which has direct links to the most number of other amino acids. 3) Threonine and methionine are interrelated
to each other and form a loop structure. 相似文献
13.
Summary. Despite the wide interest in using modified amino acids as putative biomarkers of oxidative stress, many issues remain as
to their overall reliability for early detection and diagnosis of diseases. In contrast to conventional single biomarker studies,
comprehensive analysis of biomarkers offers an unbiased strategy for global assessment of modified amino acid metabolism due
to reactive oxygen and nitrogen species. This review examines recent analytical techniques amenable for analysis of modified
amino acids in biological samples reported during 2003–2007. Particular attention is devoted to the need for validated methods
applicable to high-throughput analysis of multiple amino acid biomarkers, as well as consideration of sample pretreatment
protocols on artifact formation for improved clinical relevance. 相似文献
14.
Summary. The cDNA encoding D-aspartate oxidase (DASPO) was cloned from mouse kidney RNA by RT–PCR. Sequence analysis showed that it
contained a 1023-bp open reading frame encoding a protein of 341 amino acid residues. The protein was expressed in Escherichia coli with or without an N-terminal His-tag and had functional DASPO activity that was highly specific for D-aspartate and N-methyl-D-aspartate. To investigate the roles of the Arg-216 and Arg-237 residues of the mouse DASPO (mDASPO), we generated
clones with several single amino acid substitutions of these residues in an N-terminally His-tagged mDASPO. These substitutions
significantly reduced the activity of the recombinant enzyme against acidic D-amino acids and did not confer any additional
specificity to other amino acids. These results suggest that the Arg-216 and Arg-237 residues of mDASPO are catalytically
important for full enzyme activity. 相似文献
15.
Summary. Amino acids are widely used in biotechnology applications. Since amino acids are natural compounds, they can be safely used
in pharmaceutical applications, e.g., as a solvent additive for protein purification and as an excipient for protein formulations.
At high concentrations, certain amino acids are found to raise intra-cellular osmotic pressure and adjust to the high salt
concentrations of the surrounding medium. They are called “compatible solutes”, since they do not affect macromolecular function.
Not only are they needed to increase the osmotic pressure, they are known to increase the stability of the proteins. Sucrose,
glycerol and certain amino acids were used to enhance the stability of unstable proteins after isolation from natural environments.
The mechanism of the action of these protein-stabilizing amino acids is relatively well understood. On the contrary, arginine
was accidentally discovered as a useful reagent for assisting in the refolding of recombinant proteins. This effect of arginine
was ascribed to its ability to suppress aggregation of the proteins during refolding, thereby increasing refolding efficiency.
By the same mechanism, arginine now finds much wider applications than previously anticipated in the research and development
of proteins, in particular in pharmaceutical applications. For example, arginine solubilizes proteins from loose inclusion
bodies, resulting in efficient production of active proteins. Arginine suppresses protein–protein interactions in solution
and also non-specific adsorption to gel permeation chromatography columns. Arginine facilitates elution of bound proteins
from various column resins, including Protein-A or dye affinity columns and hydrophobic interaction columns. This review covers
various biotechnology applications of amino acids, in particular arginine. 相似文献
16.
Summary. Glucocorticoid hormones enhance the reabsorptive capacity of filtered amino acids in rat kidney, as it was shown in previous
in vivo clearance experiments. In the present study, the site of glucocorticoid action on neutral amino acid transport in superficial
nephrons of rat kidney was investigated using in vivo micropuncture technique. Adult female Wistar rats were treated with dexamethasone (DEX), and fractional excretion of L-glutamine
(L-Gln) and L-leucine (L-Leu) were determined and related to inulin after microinfusion into different nephron segments. DEX
reduced fractional excretion of both neutral amino acids as a sign of enhanced reabsorptive capacity. The site of main DEX
action on L-Leu reabsorption has been localized in the proximal straight tubule. However, in the case of L-Gln, the inhibition
of γ-glutamyltranspeptidase (γ-GT) by administration of acivicin indicated the importance of this brush border enzyme in reduced L-Gln excretion. DEX enhanced
γ-GT activity by tubular acidification. It can be presumed a DEX-inducible transport system for neutral amino acids mainly
localized in proximal straight tubules of rat kidney.
Received July 8, 1999 相似文献
17.
Summary. Aspartate is the common precursor of the essential amino acids lysine, threonine, methionine and isoleucine in higher plants.
In addition, aspartate may also be converted to asparagine, in a potentially competing reaction. The latest information on
the properties of the enzymes involved in the pathways and the genes that encode them is described. An understanding of the
overall regulatory control of the flux through the pathways is undisputedly of great interest, since the nutritive value of
all cereal and legume crops is reduced due to low concentrations of at least one of the aspartate-derived amino acids. We
have reviewed the recent literature and discussed in this paper possible methods by which the concentrations of the limiting
amino acids may be increased in the seeds. 相似文献
18.
Summary. Secondary amino acid disturbances from circulatory responses during hypoxia may cause problems in interpreting plasma amino
acid profiles of sick babies investigated for possible inherited defects. Systematic studies to characterise them are difficult
in man. We investigated the effects of hypoxia on plasma amino acids by studying 9 late gestation fetal sheep in utero during 11 one hour episodes of moderately severe isocapnic hypoxia. In 6 experiments, maternal plasma amino acids were also
monitored. Fourteen fetal plasma amino acids increased significantly, with the largest proportionate changes in alanine, valine,
leucine, isoleucine, phenylalanine, tyrosine, ornithine and lysine. Maternal amino acids did not increase. Probable explanations
were reflex peripheral vasoconstriction in skeletal muscle beds and decreased hepatic blood flow. The findings extend our
knowledge of the fetal response to hypoxic stress, demonstrate the importance of skeletal muscle in branched-chain amino acid
metabolism, and should help with interpretation of postnatal plasma amino acid disturbances.
Received January 29, 1999, Accepted February 22, 1999 相似文献
19.
Summary. The premise that free amino acid or dipeptide based diets will resolve the nutritional inadequacy of formulated feeds for
larval and juvenile fish and improve utilization of nitrogen in comparison to protein-based diets was tested in stomachless
fish, common carp (Cyprinus carpio L.) larvae. We examined the postprandial whole body free amino acid (FAA) pool in fish that were offered a FAA mixture based
diet for the duration of 2 or 4 weeks. We found that the total amount and all indispensable amino acids concentrations in
the whole body decreased after a meal. We then fed juvenile carp with dietary amino acids provided in the FAA, dipeptide (PP),
or protein (live feed organisms; brine shrimp Artemia salina nauplii, AS) forms. Histidine concentrations in the whole fish body increased in all dietary groups after feeding whereas
all other indispensable amino acids decreased in FAA and PP groups in comparison to the AS group. Taurine appears to be the
major osmotic pressure balancing free amino acid in larval freshwater fish which may indicate a conditional requirement. We
present the first evidence in larval fish that in response to synthetic FAA and PP diets, the whole body indispensable free
AA concentrations decreased after feeding. This study shows that amino acids given entirely as FAA or PP cannot sustain stomachless
larval fish growth, and may result in depletion of body indispensable AA and most of dispensable AA. The understanding of
these responses will determine necessary changes in diet formulations that prevent accelerated excretion of amino acids without
protein synthesis. 相似文献
20.
Two isoforms of chalcone synthase (CHS) were isolated from cDNA libraries derived from UV-A-irradiated anthocyanin-accumulating
(DCb) and non-accumulating (DCs) cell cultures of carrot (Daucus carota L.). The clones designated as DcCHS1, which were present only in the DCb library, had a deduced primary sequence of 389 amino
acids and an expected molecular mass of 42.7 kDa, and seem to be alleles of those cloned by Ozeki et al. (1993). The second
isoform (DcCHS2) was present in both libraries. It had the highest degree of similarity (97.7%) to parsley CHS over all 397
amino acids. The expected molecular mass of the corresponding protein was 43.6 kDa. Results obtained from Southern blot analysis
indicated the existence of at least two CHS genes in carrot. A transient enhancement of the DcCHS1 mRNA level after continuous
irradiation with UV-A light could only be observed in anthocyanin-accumulating cultures, whereas an increase in DcCHS2 mRNA
was seen in both cell lines. The maximum accumulation of CHS mRNA occurred 48 h after the onset of UV-A irradiation. In the
European wild carrot the accumulation of DcCHS1 mRNA was restricted to the red central flowers, whereas the DcCHS2 mRNA was
detectable in all red and white petals, as well as leaves, but was absent in stems and roots. The expression of DcCHS1 was
restricted to anthocyanin-accumulating cells or organs. The heterologous expression of both cDNAs in Escherichia coli resulted in immunostainable bands of different sizes on the Western blot and high levels of catalytic CHS activity.
Received: 2 September 1999 / Accepted: 30 November 1999 相似文献