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1.
Kanzelmeyer N Tsikas D Chobanyan-Jürgens K Beckmann B Vaske B Illsinger S Das AM Lücke T 《Amino acids》2012,42(5):1765-1772
Plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis from l-arginine and a cardiovascular risk factor, was found to be elevated in plasma of homocysteinemic adults. Enhanced cardiovascular
risk due to homocystinuria and impaired renal function has been found in patients with phenylketonuria (PKU) on protein-restricted
diet. However, it is still unknown whether ADMA synthesis is also elevated in children with homocystinuria due to cystathionine
beta-synthase deficiency (classical homocystinuria), and whether ADMA may play a role in phenylketonuria in childhood. In
the present study, we investigated the status of the l-arginine/NO pathway in six young patients with homocystinuria, in 52 young phenylketonuria patients on natural protein-restricted
diet, and in age- and gender-matched healthy children serving as controls. ADMA in plasma and urine was determined by GC–MS/MS.
The NO metabolites nitrate and nitrite in plasma and urine, and urinary dimethylamine (DMA), the dimethylarginine dimethylaminohydrolase
(DDAH) metabolite of ADMA, were measured by GC–MS. Unlike urine ADMA excretion, plasma ADMA concentration in patients with
homocystinuria was significantly higher than in controls (660 ± 158 vs. 475 ± 77 nM, P = 0.035). DMA excretion rate was considerably higher in children with homocystinuria as compared to controls (62.2 ± 24.5
vs. 6.5 ± 2.9 μmol/mmol creatinine, P = 0.068), indicating enhanced DDAH activity in this disease. In contrast and unexpectedly, phenylketonuria patients had significantly
lower ADMA plasma concentrations compared to controls (512 ± 136 vs. 585 ± 125 nM, P = 0.009). Phenylketonuria patients and controls had similar l-arginine/ADMA molar ratios in plasma. Urinary nitrite excretion was significantly higher in phenylketonuria as compared to
healthy controls (1.7 ± 1.7 vs. 0.7 ± 1.2 μmol/mmol creatinine, P = 0.003). Our study shows that the l-arginine/NO pathway is differently altered in children with phenylketonuria and homocystinuria. Analogous to hyperhomocysteinemic
adults, elevated ADMA plasma concentrations could be a cardiovascular risk factor in children with homocystinuria. In phenylketonuria,
the l-arginine/NO pathway seems not be altered. Delineation of the role of ADMA in childhood phenylketonuria and homocystinuria
demands further investigation. 相似文献
2.
Takashi Suzuki Masahiko Morita Toshio Hayashi 《Bioscience, biotechnology, and biochemistry》2017,81(2):372-375
We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined. 相似文献
3.
Summary. We studied the effects of l-lysine on wrap-restraint stress-induced changes in ureagenesis. An exposure to wrap-restraint stress did not affect the plasma
concentration of l-lysine, but did decrease plasma urea and arginine. Oral l-lysine (1 g/kg) blocked the effect of stress on ureagenesis, and enhanced the effect of stress on l-arginine. No influence of l-lysine were found in controls. The results imply a stress-specific, ureagenesis-stimulating effect of l-lysine, and suggest an increased requirement for l-arginine during the above conditions.
Received December 9, 2002 Accepted January 21, 2003 Published online April 3, 2003
Acknowledgement Authors thank Dr. M. Miura (Ajinomoto Co.) for his help with amino acid analysis and Dr. T. Kimura (Ajinomoto Co.) for discussions
on amino acid metabolism.
Authors' address: Dr. M. Smriga, Ajinomoto Co. Inc., Institute of Life Sciences, 1-1 Suzuki-cho, 210-8681 Kawasaki, Japan, Fax +81-44-210-5893,
E-mail: miroslav_smriga@ajinomoto.com
Abbreviations: Arg, l-arginine; Orn, l-ornithine; Lys, l-lysine; p.o., oral; WRS, wrap-restraint stress 相似文献
4.
Impaired glucose tolerance (IGT) is not associated with disturbed homocysteine metabolism 总被引:1,自引:0,他引:1
Summary. Elevated plasma total homocysteine (tHcy) has been suggested to be an additional risk factor for cardiovascular disease in
subjects with impaired glucose tolerance (IGT) and Type 2 diabetes (T2D). In order to investigate whether an insulin resistant/chronic
hyperinsulinemic situation in male diabetic and prediabetic subjects directly influences the tHcy metabolism, fasting tHcy
and post-methionine load tHcy plasma levels (PML-tHcy) were determined in 15 men with IGT, 13 men with newly dia-gnosed T2D,
and 16 normoglycemic controls (NGT). Fasting tHcy (IGT, 13.1 ± 4.6; T2D, 12.8 ± 4.0; NGT, 10.7 ± 4.4 μmol/L) and PML-tHcy (IGT, 46.5 ± 17.39; T2D, 41.1 ± 6.8; NGT, 38.0 ± 9.7 μmol/L) showed no differences between the groups. Fasting tHcy and PML-tHcy correlated with fasting proinsulin (r = 0.395,
p < 0.05; r = 0.386, p< 0.05) and creatinine (r = 0.489, p < 0.01; r = 0.339, p < 0.05), resp. Multiple regression analysis
showed only a relationship between fasting tHcy and creatinine. No relationships have been found between fasting tHcy and
PML-tHcy, resp., and indicators of an insulin resistant state, e.g., insulin and proinsulin, as well as serum cobalamin and
folate concentrations. In conclusion, our data suggest that the degree of glucose intolerance has no direct impact on the
metabolism of homocysteine. However, tHcy levels tend to be elevated with the development of nephropathy, indicating an association
between tHcy and renal function in these subjects.
Received May 11, 1999 相似文献
5.
Evidence for NO-dependent vasodilation in the trout (Oncorhynchus mykiss ) coronary system 总被引:1,自引:0,他引:1
T. Mustafa C. Agnisola J. K. Hansen 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1997,167(2):98-104
The effects of l-arginine, and its analogues N
ω-nitro-l-arginine methyl ester and N
ω-nitro-l-arginine on vascular resistance were investigated in the intact coronary system of an isolated non-working trout heart preparation.
l-Arginine, at 10–8 mol · l–1induced a slight vasodilatory effect (max 10%). N
ω-nitro-l-arginine methyl ester and N
ω-Nitro-l-arginine in the range 10–8–10–4 mol · l–1 caused dose-dependent increases in coronary resistance. The vasodilatory action of l-arginine was abolished when the preparation was pretreated with 10–4 mol · l–1
N
ω-nitro-l-arginine or N
ω-nitro-l-arginine methyl ester. Nitroprusside alone at 1 mmol · l–1 induced a maximum vasodilation (30%) of the coronary system. Methylene blue a known inhibitor of guanylate cyclase, induced
a strong vasoconstriction (already significant at 10–5 mol · l–1) and was able to overcome the vasodilative effect of nitroprusside. The endothelial nitric oxide agonists acetylcholine and
serotonin, established in mammalian vessels, also mediate vasodilation in trout coronary system. In 50% of preparations, acetylcholine
induced a biphasic response with vasodilation at low concentration (max 15% at 10–8 mol · l–1). Serotonin displayed a dose-response vasodilation in the range 10–8–10–4 mol · l–1 (max 20%). These vasodilative effects were reduced or abolished by 10–4 mol · l–1
l-NA. These data support the existence of NO-mediated vasodilation mechanisms in the trout coronary system.
Accepted: 1 July 1996 相似文献
6.
Taste cells are specialized epithelial cells that respond to stimulation with release of neurotransmitters onto afferent nerves
that innervate taste buds. In analogy to neurotransmitter release in other cells, it is expected that neurotransmitter release
in taste cells is dependent on an increase in intracellular Ca2+ ([Ca2+]
i
). We have studied changes in [Ca2+]
i
elicited by the taste stimuli l- and d-arginine in isolated taste cells from the channel catfish (Ictalurus punctatus). In a sample of 119 cells, we found 15 cells responding to l-arginine, and 12 cells responding to d-arginine with an increase in [Ca2+]
i
. The response to l-arginine was inhibited by equimolar d-arginine in cells where d-arginine alone did not cause a change in [Ca2+]
i
, which is consistent with mediation of this response by a previously characterized l-arginine-gated nonspecific cation channel antagonized by d-arginine [31]. However, we also found that these taste stimuli elicited decreases in [Ca2+]
i
in substantial number of cells (6 for l-Arg, and 2 for d-Arg, n= 119). These observations suggest that stimulation of taste cells with sapid stimuli may result in simultaneous excitation
and inhibition of different taste cells within the taste bud, which could be involved in local processing of the taste signal.
Received: 25 May 1995/Revised: 29 September 1995 相似文献
7.
Marie-Louise Svensson Kristoffer Valeria Sten Gatenbeck 《Archives of microbiology》1981,129(3):210-212
It was found that hydroxyurea, l-arginine and l-citrulline respectively significantly stimulated the formation of d-cycloserine in Streptomyces garyphalus. The formation of [14C]-hydroxyurea by washed cells was demonstrated after incubation with l-[guanido-14C]-arginine and l-[ureido-14C]-citrulline. The 15N of H2NCO15NHOH was incorporated to 40% in d-cycloserine. The mass spectrum as well as the 15N NMR spectrum of labelled N,2-dicarbobenzyloxy-d-cycloserine derived from [15N]-hydroxyurea showed that hydroxyurea was the source of the heterocyclic nitrogen in the biosynthesis of d-cycloserine. 相似文献
8.
The uptake ofl-[3H]arginine into synaptosomes prepared from rat cerebellum and cortex occurred by a high-affinity carrier-mediated process.
The uptake of arginine appeared to be potentiated by removal of extracellular Na+, inhibited by high levels of extracellular K+, but not by depolarization with veratridine or 4-amino pyridine. The effect of Na+ removal or K+ elevation did not seem to be due to changes in intracellular Ca2+ or pH. In both brain regions, uptake was significantly inhibited byl-arginine,l-lysine,l-ornithine, andl-homoarginine, but not byd-arginine norl-citrulline. Uptake was also inhibited by NG-monomethyl-l-arginine acetate, but not by NG-nitro-l-arginine methyl ester nor NG-nitro-l-arginine except in the cortex at a concentration of 1 mM. The results indicate that the carrier system operating in synaptosomes
showed many of the characteristics of the ubiquitous y+ system seen in many other tissues, although its apparent sensitivity to variations in extracellular Na+ was unusual. 相似文献
9.
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
10.
Sosnowski P Krauss H Bogdanski P Suliburska J Jablecka A Cieslewicz A Pupek-Musialik D Jastak R 《Journal of physiology and biochemistry》2012,68(1):1-9
Due to the complex mechanisms of l-arginine activity, it is difficult to determine the clinical significance of supplementation with this amino acid. The objective
of this study was to determine the influence of short-term supplementation with l-arginine in stress conditions, induced by ischemia–reperfusion syndrome, by assessing the damage to muscular and hepatic
cells on the basis of creatine kinase (CK), alanine aminotransferase (ALAT) and aspartic aminotransferase (AspAT) activity
in blood and the level of oxygen free radicals in analyzed tissues of rats. We observed that induced ischemia of hind limb
caused an increase in CK, ALAT and AspAT activity and an increase in the level of free radicals in liver, but not in skeletal
muscle. Supplementation with l-arginine led to a reduction in serum activity of CK and AspAT and reduction of the level of free radicals in analysed tissues.
Simultaneous supplementation with l-arginine AND l-NAME resulted in a reversal of changes induced by l-arginine supplementation in the case of AspAT and free radicals in skeletal muscle. The results indicate that under conditions
of ischemia–reperfusion, short-term administration of l-arginine has a protective effect on skeletal muscle manifesting itself by reduction of CK in the serum and reduction of free
radicals level in THIS tissue. 相似文献
11.
The effect of l-arginine on transepithelial ion transport was examined in cultured M-1 mouse renal cortical collecting duct (CCD) cells using
continuous short circuit current (I
SC
) measurements in HCO3
−/CO2 buffered solution. Steady state I
SC
averaged 73.8 ± 3.2 μA/cm2 (n= 126) and was reduced by 94 ± 0.6% (n= 16) by the apical addition of 100 μm amiloride. This confirms that the predominant electrogenic ion transport in M-1 cells is Na+ absorption via the epithelial sodium channel (ENaC). Experiments using the cationic amino acid l-lysine (radiolabeled) as a stable arginine analogue show that the combined activity of an apical system y+ and a basal amino acid transport system y+L are responsible for most cationic amino acid transport across M-1 cells. Together they generate net absorptive cationic
amino acid flux. Application of l-arginine (10 mm) either apically or basolaterally induced a transient peak increase in I
SC
averaging 36.6 ± 5.4 μA/cm2 (n= 19) and 32.0 ± 7.2 μA/cm2 (n= 8), respectively. The response was preserved in the absence of bath Cl− (n= 4), but was abolished either in the absence of apical Na+ (n= 4) or by apical addition of 100 μm amiloride (n= 6). l-lysine, which cannot serve as a precursor of NO, caused a response similar to that of l-arginine (n= 4); neither L-NMMA (100 μm; n= 3) nor L-NAME (1 mm; n= 4) (both NO-synthase inhibitors) affected the I
SC
response to l-arginine. The effects of arginine or lysine were replicated by alkalinization that mimicked the transient alkalinization
of the bath solution upon addition of these amino acids. We conclude that in M-1 cells l-arginine stimulates Na+ absorption via a pH-dependent, but NO-independent mechanism. The observed net cationic amino acid absorption will counteract
passive cationic amino acid leak into the CCD in the presence of electrogenic Na+ transport, consistent with reports of stimulated expression of Na+ and cationic amino acid transporters by aldosterone.
Received: 11 September 2000/Revised: 6 December 2000 相似文献
12.
Summary. Hydrogensquarates of dipeptide l-threonyl-l-serine (H-Thr-Ser-OH) and l-serine (HSq × Ser) have been synthesized, isolated and spectroscopic characterized by solid-state linear-polarized IR-spectroscopy, 1H- and 13C-NMR, ESI-MS and HPLC with tandem masspectrometry (MS-MS) methods. The structures of the salts and neutral dipeptide have
been predicted theoretically by ab initio calculations. In the case of H-Thr-Ser-OH the theoretical data are supported by IR-LD ones. The hydrogensquarates consist in positive charged dipeptide or amino acid
moiety and negative hydrogensquarate anion (HSq) stabilizing by strong intermolecular hydrogen bonds. The data about the l-serine hydrogensquarate are compared with known crystallographic data thus indicating a good correlation between the theoretical
predicted structures and experimentally obtained by single crystal X-ray diffraction. 相似文献
13.
M. Torras-Llort R. Ferrer J.F. Soriano-García M. Moretó 《The Journal of membrane biology》1996,152(3):183-193
The properties of l-lysine transport in chicken jejunum have been studied in brush border membrane vesicles isolated from 6-wk-old birds. l-lysine uptake was found to occur within an osmotically active space with significant binding to the membrane. The vesicles
can accumulate l-lysine against a concentration gradient, by a membrane potential-sensitive mechanism. The kinetics of l-lysine transport were described by two saturable processes: first, a high affinity-transport system (K
mA= 2.4 ± 0.7 μmol/L) which recognizes cationic and also neutral amino acids with similar affinity in the presence or absence
of Na+ (l-methionine inhibition constant KiA, NaSCN = 21.0 ± 8.7 μmol/L and KSCN = 55.0 ± 8.4 μmol/L); second, a low-affinity transport mechanism (KmB= 164.0 ± 13.0 μmol/L) which also recognizes neutral amino acids. This latter system shows a higher affinity in the presence
of Na+ (KiB for l-methionine, NaSCN = 1.7 ± 0.3 and KSCN = 3.4 ± 0.9 mmol/L). l-lysine influx was significantly reduced with N-ethylmaleimide (0.5 mmol/L) treatment. Accelerative exchange of extravesicular labeled l-lysine was demonstrated in vesicles preloaded with 1 mmol/L l-lysine, l-arginine or l-methionine. Results support the view that l-lysine is transported in the chicken jejunum by two transport systems, A and B, with properties similar to those described
for systems b
0,+ and y+, respectively.
Received: 14 August 1995/Revised: 2 April 1996 相似文献
14.
Effects of high salt diets and taurine on the development of hypertension in the stroke-prone spontaneously hypertensive rat 总被引:3,自引:0,他引:3
Summary. Taurine is present in high concentrations in mammalian tissues and has been implicated in cardiovascular control mechanisms.
The aim of the present study was to evaluate the ability of taurine to attenuate salt-induced elevations in blood pressure
and markers of damage to the kidney and cardiovascular system in stroke prone spontaneously hypertensive rats (SPSHR). Male
SPSHR (6 weeks old) were placed on high salt diets that contained 1% (w/w) NaCl added to their normal chow for 84 days and
then were switched to 3% added NaCl for the remaining 63 days of the study. SPSHR was given 1.5% taurine in the drinking water
(n = 8), a taurine free diet (n = 8) or normal chow (n = 8). A final control group (n = 6) was not given high salt diets.
High salt diets caused an acceleration in the development of hypertension in all groups. Taurine supplementation reduced ventricular
hypertrophy and decreased urinary excretion of protein and creatinine. The taurine free diet did not alter serum or urinary
excretion of taurine, but did result in elevated urinary nitrogen excretion, increased serum cholesterol levels, and impaired
performance in a spatial learning task. Alterations in dietary taurine intake did not alter urinary or serum electrolytes
(Na+, K+), but taurine supplementation did attenuate a rise in serum calcium seen with the high salt diets. Urinary excretion (μg/24
h) of epinephrine and dopamine was significantly reduced in SPSHR given 1% NaCl in the diet, but this effect was not seen
in SPSHR on taurine free or supplemented diets. Taurine supplementation showed cardioprotective and renoprotective effects
in SPSHR given high salt diets.
Received April 12, 1999/Accepted September 13, 1999 相似文献
15.
Onaga T Nagashima C Sakata T 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2000,170(5-6):469-479
The present study evaluated the role of nitric oxide in the regulation of duodenal motility and pancreatic exocrine secretion
in conscious sheep. Intravenous infusions of nitric oxide synthase inhibitors, Nω-nitro-l-arginine-methyl ester (l-NAME) and Nω-nitro-l-arginine, induced clusters of duodenal contractions like phase III of migrating motor complexes and simultaneously inhibited
flow rate, bicarbonate ion and enzyme outputs of pancreatic juice. The effects of l-NAME were inhibited by simultaneous infusion of l-arginine, but not altered by adrenergic blockade using a combined infusion of phentolamine and propranolol. Inhibition of
the pancreatic secretion occurred in coincidence with initiation of the duodenal contractions, while the pancreatic secretion
was not inhibited when the premature duodenal contractions were abolished by the l-arginine infusion. The initiation of the cluster of duodenal contractions by l-NAME was not abolished by background infusion of atropine, whereas the amplitude of contractions was significantly inhibited
by atropine. These results suggest that intrinsic nitric oxide plays a crucial role in the regulation of duodenal tone and
maintenance of continuous secretion by the exocrine pancreas in sheep. These results also implied that inhibition of pancreatic
exocrine secretion by the nitric oxide synthase inhibitor is presumably mediated in part through the contractile effect on
the duodenum.
Accepted: 27 June 2000 相似文献
16.
T. M. Sossong Jr. Sergei V. Khangulov R. C. Cavalli Dianne Robert Soprano G. C. Dismukes D. E. Ash 《Journal of biological inorganic chemistry》1997,2(4):433-443
Rat liver arginase contains a dinuclear Mn2(II,II) center in each subunit having EPR properties similar to those observed in Mn-catalases. The principal physiologic
role of arginase is catalyzing the hydrolytic cleavage of l-arginine to produce l-ornithine and urea. Here we demonstrate that arginase catalyzes the disproportionation of hydrogen peroxide by a redox mechanism
analogous to Mn-catalases, but at rates that are 10–5 to 10–6 of k
cat for the Mn-catalases, and also exhibits peroxidase activity. The dinuclear Mn2(II,II) center is essential for maximal catalase activity, since both the H101N and H126N mutant arginases containing only
one Mn(II)/subunit have catalase activities that are <3% of that for the wild-type enzyme. Like the Mn-catalases, the catalase
activity of arginase is not inhibited by millimolar concentrations of CN–, the most potent inhibitor of heme catalases, or by EDTA, a chelator of free metal ions. The catalase activity of arginase
is not significantly inhibited by Cl– or F–, in contrast to Mn-catalases, while potent inhibitors of the hydrolytic activity are also effective inhibitors of the catalase
activity. These results suggest that lower affinity of hydrogen peroxide to the active site of arginase contributes to the
lower catalase activity. EPR spectroscopy reveals that potent inhibitors of the hydrolytic reaction, including N
ω-hydroxy-l-arginine, l-lysine, and l-valine, decouple the electronic interaction between the Mn2+ ions, most probably by removing a μ-bridging ligand or by increasing the intermanganese separation. The capacity for arginase
to deliver a hydroxide ion to hydrolyze the l-arginine substrate is suggested to arise from a "dinuclear effect", wherein the two metal ions contribute more or less equivalently
in deprotonation of metal-bound water molecule. Structure-reactivity analyses of these reactions will provide insights into
the factors that control redox versus hydrolytic function in dimanganese clusters.
Received: 18 November 1996 / Accepted: 7 April 1997 相似文献
17.
The tryptophan auxotroph mutant trp3-1 of Arabidopsis thaliana (L.) Heynh., despite having reduced levels of l-tryptophan, accumulates the tryptophan-derived glucosinolate, glucobrassicin and, thus, does not appear to be tryptophan-limited.
However, due to the block in tryptophan synthase, the mutant hyperaccumulates the precursor indole-3-glycerophosphate (up
to 10 mg per g FW). Instability of indole-3-glycerophosphate leads to release of indole-3-acetic acid (IAA) from this metabolite
during standard workup of samples for determination of conjugated IAA. The apparent increase in “conjugated IAA” in trp3-1 mutant plants can be traced back entirely to indole-3-glycerophosphate degradation. Thus, the levels of neither free IAA
nor conjugated IAA increase detectably in the trp3-1 mutant compared to wild-type plants. Precursor-feeding experiments to shoots of sterile-grown wild-type plants using [2H]5-l-tryptophan have shown incorporation of label from this precursor into indole-3-acetonitrile and indole-3-acetic acid with
very little isotope dilution. It is concluded that Arabidopsis thaliana shoots synthesize IAA from l-tryptophan and that the non-tryptophan pathway is probably an artifact.
Received: 1 March 2000 / Accepted: 10 April 2000 相似文献
18.
Dušan Sokolovic Gordana Bjelakovic Jelenka Nikolic Boris Djindjic Dusica Pavlovic Gordana Kocic Ivana Stojanovic Voja Pavlovic 《Amino acids》2010,38(1):339-345
Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The
aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic
cholestasis and the effects of l-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with l-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with l-arginine. Increased plasma γ-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin
levels in BDL rats were reduced by administration of l-arginine (P < 0.001). Cholestasis increased the brain’s putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of l-arginine in BDL rats prevents metabolic disorders of polyamines and establishs a neuroprotective role in the brain during
cholestasis. 相似文献
19.
Sitta A Barschak AG Deon M de Mari JF Barden AT Vanzin CS Biancini GB Schwartz IV Wajner M Vargas CR 《Cellular and molecular neurobiology》2009,29(2):211-218
Aims
l-Carnitine exerts an important role by facilitating the mitochondrial transport of fatty acids, but is also a scavenger of
free radicals, protecting cells from oxidative damage. Phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism,
is currently treated with a special diet consisting of severe restriction of protein-enriched foods, therefore potentially
leading to l-carnitine depletion. The aim of this study was to determine l-carnitine levels and oxidative stress parameters in blood of two groups of PKU patients, with good and poor adherence to
treatment. Methods Treatment of patients consisted of a low protein diet supplemented with a synthetic amino acids formula not containing Phe,
l-carnitine, and selenium. l-Carnitine concentrations and the oxidative stress parameters thiobarbituric acid reactive species (TBARS) and total antioxidant
reactivity (TAR) were measured in blood of the two groups of treated PKU patients and controls. Results We verified a significant decrease of serum l-carnitine levels in patients who strictly adhered to the diet, as compared to controls and patients who did not comply with
the diet. Furthermore, TBARS measurement was significantly increased and TAR was significantly reduced in both groups of phenylketonuric
patients relatively to controls. We also found a significant negative correlation between TBARS and l-carnitine levels and a significant positive correlation between TAR and l-carnitine levels in well-treated PKU patients. Conclusions Our results suggest that l-carnitine should be measured in plasma of treated PKU patients, and when a decrease of this endogenous component is detected
in plasma, supplementation should be considered as an adjuvant therapy. 相似文献
20.
Summary. Our aim was to determine changes in free amino acid (FAA) and dipeptide (DP) concentrations in probable Alzheimer’s disease
(pAD) subjects compared with control (CT) subjects using liquid chromatography and electrospray ionization tandem mass spectrometry
(LCMS2). We recruited gender- and age-matched study participants based on neurological and neuropsychological assessments. We measured
FAAs and DPs in cerebrospinal fluid (CSF), plasma and urine using LCMS2 with selected reaction monitoring (SRM). Imidazole-containing FAAs (histidine, methyl-histidine), catecholamines (L-DOPA
and dopamine), citrulline, ornithine, glycine and antioxidant DPs (carnosine and anserine) accounted for the major changes
between CT and pAD. Carnosine levels were significantly lower in pAD (328.4 ± 91.31 nmol/dl) than in CT plasma (654.23 ± 100.61 nmol/dl).
In contrast, L-DOPA levels were higher in pAD (1400.84 ± 253.68) than CT (513.10 ± 121.61 nmol/dl) plasma. These data underscore
the importance of FAA and DP metabolism in the pathogenesis of AD. Since our data show changes in antioxidants, neurotransmitters
and their precursors, or FAA associated with urea metabolism in pAD compared with CT, we propose that manipulation of these
metabolic pathways may be important in preventing AD progression. 相似文献