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1.
Abstract: 4-Hydroxy-3-methoxyphenylglycol (HMPG) labelled with three deuterium atoms was used to study the disposition of peripherally administered HMPG. Five healthy men were given an intravenous pulse dose of 4.3 μmol of labelled HMPG and subsequent plasma and urine levels of endogenous and labelled HMPG as well as those of 4-hydroxy-3-methoxymandelic acid (HMMA, VMA) were determined by gas chromatography-mass spectrometry, using selected ion detection. Approximately 40% of the injected amount of deuterium-labelled HMPG was recovered in the urine as HMMA and another 40% was eliminated as HMPG conjugates. Thus, the HMPG formed from norepinephrine either in the central or peripheral nervous system undergoes both conjugation and extensive oxidation.  相似文献   

2.
Abstract: 4-Hydroxy-3-methoxymandelic acid (HMMA; VMA) labeled with three deuterium atoms was used to study the turnover and fate of HMMA following intravenous injection. Five healthy men were given a pulse dose of 5.0 μmol of labeled HMMA. Plasma and urinary levels of both endogenous and labeled HMMA were subsequently followed by gas chromatography-mass spectrometry using selected ion detection. The kinetic parameters were determined both with and without compensation for the pool expansion caused by the injection of labeled HMMA. The urinary recovery of labeled HMMA was 85 × 10% (mean ± SD). No conversion of HMMA t o 4-hydroxy-3-methoxyphenyl glycol (HMPG) occurred. The biological half-life of HMMA was 0.54 ± 0.22 h. The apparent volume of distribution was 0.36 ± 0.11 L/kg. The production rate or body turnover was 1.27 ± 0.51 μmol HMM/h and urinary excretion rate was 0.82 ± 0.22 μmol/h. These results show that HMMA is turning over rapidly in a relatively small volume of distribution and that, unlike HMPG, it is an end metabolite of norepinephrine in man.  相似文献   

3.
Abstract: D, L(±)-4-Hydroxy-3-methoxyphenylglycol (HMPG) labelled with three deuterium atoms was used to study turnover of plasma free HMPG following an intravenous injection. Ten healthy men were given a pulse dose of either 4.3 μmol or 2.2 μmol of labelled HMPG ([2H3]HMPG piperazine salt). Plasma and urine levels of both endogenous and labelled HMPG were subsequently followed by gas chromatography-mass spectrometry with selected ion detection. Kinetic calculations based upon a single-compartment model were consistent with a monoexponential elimination of plasma free HMPG. The half-life of HMPG was 0.46 and 0.78 h (mean values in the two dose groups). The HMPG production rate was 2.01 and 2.35 μmol/hour, and the urinary excretion rate of HMPG (free and conjugated) was 0.48 and 0.47 μmol/h. The endogenous plasma level of free HMPG was 25 and 33 nmol/L. The results show that HMPG turns over rapidly and that HMPG is further metabolized extensively. About one-fourth of the HMPG produced is excreted in urine as free and conjugated HMPG.  相似文献   

4.
Abstract: 4-Hydroxy-3-methoxyphenylglycol (HMPG) labelled with 14C was used to study the metabolic fate of HMPG in six healthy volunteers. Besides conjugation and oxidation to 4-hydroxy-3-methoxymandelic acid (HMMA, VMA) a minor portion, 8.4 ± 1.1% (mean ± SEM) was excreted as 14C-labelled vantllic acid (VA). To study if VA was formed from HMPG or HMMA (VMA), deuterium-labelled HMPG ([2H3]HMPG) and HMMA ([2H6]HMMA) were simultaneously injected intravenously to seven healthy volunteers. The recovery of [2H3]VA from [2H3]HMPG was 8.3 ± 2.1% and the recovery of [2H6]VA from [2H6]HMMA was 9.0 ± 2.1%. The 2H-labelled VAs were probably formed by a decar boxylation reaction, in the case of HMPG after previous oxidation to HMMA.  相似文献   

5.
The in vivo oxidation of the norepinephrine metabolite 4-hydroxy-3-methoxyphenylglycol (HMPG) to 4-hydroxy-3-methoxymandelic acid was studied in man with two different doses of deuterium-labeled HMPG and a tracer dose of [14C]HMPG. HMPG oxidation appeared to be dose-dependent with an oxidation of 62-70% for doses below or equal to 2.2 mumol. With the use of a capillary column coated with an optically active phase (Chirasil-Val) and gas chromatography mass-spectrometry the human urinary excretions of the two stereoisomers of deuterium-labelled HMPG (free + conjugates) were found to be equal.  相似文献   

6.
Administration of insulin (2 IU/kg, i.p.) produced a significant decrease (18%) in forebrain norepinephrine and a significant increase in the major metabolite of norepinephrine, 3-methoxy-4-hydroxyphenylglycol-sulfate (MOPEG-SO4, +19%) in rats. Streptozotocin-induced diabetes produced the opposite effects, resulting in an increase in forebrain norepinephrine (+17%) and a decrease in MOPEG-SO4 (-26%). In addition, insulin increased (+143%) and diabetes decreased (-41%) the turnover rate of norepinephrine, as measured by the rate of decrease of norepinephrine following inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine. All of these effects in diabetic rats were reversed by insulin replacement therapy. These data are discussed within the context of mood disorders characteristic of diabetic patients.  相似文献   

7.
Methylxanthines can produce behavior resembling opiate withdrawal in rats. Since previous studies have demonstrated the involvement of central noradrenergic systems during naloxone-precipitated withdrawal, the effects of 3-isobutyl-1-methylxanthine (IBMX) on norepinephrine metabolism in rat brain were studied. It was found that administration of IBMX elevated levels of the major norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in areas innervated by the locus coeruleus. The increases in MHPG was noted 1 h after administration and was maximal (270% of control) after 3 h. Levels of another norepinephrine metabolite, 3,4-dihydroxyphenylglycol, followed a similar pattern and time course. Coadministration of naloxone with IBMX did not affect the IBMX-induced elevation in MHPG. Administration of the alpha-agonist clonidine, however, antagonized the effects of IBMX on MHPG levels. The effects of IBMX and clonidine were dose dependent; the lowest dose of IBMX needed to elevate MHPG was 30 mumol/kg (i.p.), and clonidine (180 nmol/kg) reduced the effect of IBMX (100 mumol/kg) by 50%. The data, discussed in terms of a methylxanthine-noradrenergic interaction, suggest that withdrawal behaviors in general may be subserved by hyperactive noradrenergic neurons.  相似文献   

8.
Abstract: A gas chromatographic-mass spectrometric assay, which allowed simultaneous measurement of 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG), was used to show that the concentration of MHPG in primate CNS far exceeded that of DHPG and that both metabolites were mainly in the unconjugated form. In rat brain, DHPG concentration was generally higher than that of MHPG, and both existed predominantly as conjugates. Rat and primate plasma contained more MHPG than DHPG. In plasma of primates but not of rats, higher proportions of the metabolites were conjugated, compared to those in brain. Significant correlations existed between MHPG and DHPG in rat brain, monkey brain, human plasma, and both monkey CSF and plasma. In monkeys, a significant CSF-plasma correlation was found for MHPG, but not for DHPG. Acute administration of piperoxane raised rat brain MHPG and DHPG concentration; desipramine prevented this rise in DHPG, but not in MHPG. Desipramine alone decreased DHPG, but not MHPG, concentration. Piperoxane increased monkey brain MHPG, but not DHPG, concentration. These data suggest that DHPG is a valuable metabolite to measure when assessing norepinephrine metabolism in the rat. Under certain conditions, measurement of rat brain MHPG and DHPG may provide information concerning the site of norepinephrine metabolism. However, in primates the importance of monitoring DHPG, in addition to MHPG, is uncertain.  相似文献   

9.
Gas chromatography-mass spectrometry evidence is presented for the presence of both phenylacetic acid (PAA) and 3-indoleacetic acid (IAA) in vegetative and fertile tissues of the sporophyte of the ostrich fern [ Matteucia struthiopteris (L.) Todaro]. 3-Indolepropionic acid, tryptamine and 3-indoleacetonitrile were not found in tissue extracts, although small amounts of 3-indolebutyric acid and tryptophol may have been present. PAA was present in amounts higher than those found in flowering plants, while LAA levels fall within the angiosperm range. The levels of both auxins were higher in the younger vegetative tissues than in mature vegetative or fertile pinnae. Recent evidence for the occurrence of angiosperm growth hormones in ferns is discussed.  相似文献   

10.
Abstract: Homovanillie acid (HVA) labeled with either two or five deuterium atoms (d2-HVA or d5-HVA) was used to label the peripheral body pool of endogenous HVA (d0-HVA) in control humans and in neurological patients. Either d2- or d5-HVA was rapidly injected intravenously and concentrations of d2- or d5- and d0-HVA in sequential samples of blood plasma were determined by gas chromatography-mass spectrometry (GC-MS). Parameters describing the distribution and elimination of HVA, as well as its pool size, turnover, and synthesis rate were then calculated. Results indicate that the decline of plasma d2- or d5-HVA with time was multiexponential in five out of six subjects. Basal levels of endogenous HVA averaged 14.4 ± 1.3 ng/ml in the control patients and 8.69 ± 2.4 ng/ml in the neurological patients. The biological half-life averaged 71.3 ± 8.0 min in the control subjects and 91.3 ± 15 min in the neurological patients. The apparent volume of distribution of HVA in the body was 31–100 liters. Plasma clearance was 243–679 ml/min. The size of the peripheral body pool, calculated from plasma kinetic parameters, was 392–673 μg. The HVA rate of production, calculated for the whole body, was 166–323 μg/h. This technique can be used to determine accurately the rate of HVA production by the whole body over short time intervals. Since sample size was very limited ( n = 3 per group) and effects of variables such as age and sex on these data have not been excluded, more thorough investigations are needed to document any differences between normal controls and neurological patients.  相似文献   

11.
Brain Quinolinic Acid in Huntington''s Disease   总被引:6,自引:4,他引:2  
Concentrations of the endogenous neurotoxic tryptophan metabolite, quinolinic acid (QA), were measured in postmortem brain tissue obtained from patients with Huntington's disease (HD) and matched controls, using a gas chromatography/mass spectrometry method. There was no significant difference in either the putamen or the frontal cortex between the HD and control groups. These results do not support the hypothesis that increased QA is responsible for neuronal degeneration in HD.  相似文献   

12.
3-Hydroxy-3-methylglutaryl-coenzyme A lyase (HL) deficiency is characterized by tissue accumulation of 3-hydroxy-3-methylglutaric (HMG), and 3-methylglutaric (MGA) acids. Affected patients present cardiomyopathy, whose pathomechanisms are not yet established. We investigated the effects of HMG and MGA on energy and redox homeostasis in rat heart using in vivo and in vitro models. In vivo experiments showed that intraperitoneal administration of HMG and MGA decreased the activities of the respiratory chain complex II and creatine kinase (CK), whereas HMG also decreased the activity of complex II–III. Furthermore, HMG and MGA injection increased reactive species production and carbonyl formation, and decreased glutathione concentrations. Regarding the enzymatic antioxidant defenses, HMG and MGA increased glutathione peroxidase (GPx) and glutathione reductase (GR) activities, while only MGA diminished the activities of superoxide dismutase (SOD) and catalase, as well as the protein content of SOD1. Pre-treatment with melatonin (MEL) prevented MGA-induced decrease of CK activity and SOD1 levels. In vitro results demonstrated that HMG and MGA increased reactive species formation, induced lipid peroxidation and decreased glutathione. We also verified that reactive species overproduction and glutathione decrease provoked by HMG and MGA were abrogated by MEL and lipoic acid (LA), while only MEL prevented HMG- and MGA-induced lipoperoxidation. Allopurinol (ALP) also prevented reactive species overproduction caused by both metabolites. Our data provide solid evidence that bioenergetics dysfunction and oxidative stress are induced by HMG and MGA in heart, which may explain the cardiac dysfunction observed in HL deficiency, and also suggest that antioxidant supplementation could be considered as adjuvant therapy for affected patients.  相似文献   

13.
Jarvis AP  Schaaf O  Oldham NJ 《Planta》2000,212(1):119-126
Stable-isotope-labelled (2H6,18O) 3-hydroxy-3-phenylpropanoic acid, a putative intermediate in the biosynthesis of benzoic acid (BA) and salicylic acid (SA) from cinnamic acid, has been synthesized and administered to cucumber (Cucumis sativus L.) and Nicotiana attenuata (Torrey). Analysis of the products by gas chromatography-mass spectrometry revealed incorporation of labelling into BA and SA, but not into benzaldehyde. In a separate experiment, 3-hydroxy- 3-phenylpropanoic acid was found to be a metabolite of phenylalanine, itself the primary metabolic precursor of BA and SA. These data suggest that cinnamic acid chain shortening is probably achieved by β-oxidation, and that the proposed “non-oxidative” pathway of side-chain degradation does not function in the biosynthesis of BA and SA, in cucumber and N. attenuata. Received: 10 February 2000 / Accepted: 18 April 2000  相似文献   

14.
4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated. Excretion studies were conducted with oral applications of 100mg of 4-hydroxyandrostenedione or 200mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry. Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3beta-hydroxy-5alpha-androstane-4,17-dione (2) and 3alpha-hydroxy-5beta-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3xi,4xi-dihydroxy-5xi-androstan-17-one (4, 6-11) except 3alpha,4alpha-dihydroxy-5beta-androstan-17-one (5). Out of the 17beta-hydroxylated analogs 4-hydroxytestosterone (18), 3beta,17beta-dihydroxy-5alpha-androstan-4-one (19), 3alpha,17beta-dihydroxy-5beta-androstan-4-one (20), 5alpha-androstane-3beta,4beta,17beta-triol (21), 5alpha-androstane-3alpha,4beta,17beta-triol (26) and 5alpha-androstane-3alpha,4alpha,17beta-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as oxidation products. Conjugation was diverse and included glucuronidation and sulfatation.  相似文献   

15.
A facile preparation is described of 3-(indol-3-yl)-2-hydroxy-4-hydroxymethylcyclopent-2-enone and its N-derivatives in 15-40% yields by the degradation of ascorbigen or its N-derivatives in a warm solution of L-ascorbic acid through a sequential domino reaction. The same cyclopentenone derivatives were obtained in 30-40% yields by the condensation of (N-alkylindol-3-yl)glycolic acids with ascorbic acid. 2,6-Dihydroxy-1-(indol-3-yl)hexa-1,4-diene-3-one and 2-hydroxy-4-hydroxymethyl-5-(indol-3-yl)cyclopent-2-enone were identified as intermediates in this reaction.  相似文献   

16.
Abstract Five Clostridium butyricum strains of different origin were grown in trypticase-yeast extract-hemin medium with or without d-glucose (TGYH or TYH medium, respectively) and in a synthetic basal medium with d-glucose (BMG medium). 2-Hydroxy-4-methylpentanoic acid was detected by gas chromatography-mass spectrometry (GC-MS) for the five strains whether grown in TGYH or TYH medium (270 or 170 μM, respectively). In BMG medium supplemented with l-leucine (10 mM), the concentration of this metabolite was strongly increased (2.8 mM versus 10 μM in the control). After culture in TGYH or TYH medium supplemented with l-( methyl -2H3)leucine, 2-hydroxy-4-([2H3]methyl)pentanoic acid was detected by GC-MS. This observation demonstrates that C. butyricum is able to convert l-leucine into the corresponding 2-hydroxy acid and opens a new aspect in the study of C. butyricum metabolism.  相似文献   

17.
Abstract: The mouse brain contains 12.5 and 4.1 ng/g of p- and m -hydroxyphenylacetic acids, respectively. The hydroxyphenylacetic acids were isolated by chromatography on DEAE-Sephadex A-25 and quantitated as their pentafluoropropionyl and hexafluoropropanol esters by use of a gas chromatograph equipped with an electron-capture detector. The highest concentrations of p- or m -hydroxyphenylacetic acids were observed in the caudate nuclei (27.9 and 8.7 ng/g, respectively) and olfactory tubercles (20.2 and 5.3 ng/g, respectively). The identities of the p- and m -hydroxyphenylacetic acids were further confirmed as a consequence of the reductions observed following monoamine oxidase inhibition or the increases observed in the appropriate acid following the parenteral administration of p- or m -tyramine.  相似文献   

18.
4-Chloroindole-3-acetic acid methyl ester was identified unequivocally in Lathyrus latifolius L., Vicia faba L. and Pisum sativum L. by thin layer chromatography, gas chromatography and mass spectrometry. The gas chromatographic system was able to separate underivatized chloroindole-3-acetic acid methyl ester isomers. The quantitative determination of 4-chloroindole-3-acetic acid methyl ester in immature seeds of these three species was performed by gas chromatography – mass spectrometry using deuterium labelled 4-chloro-indole-3-acetic acid methyl ester as an internal standard. P. sativum contained approximately 25 mg kg-1, V. faba 1–2 mg kg-1 and L. latifolius 2 mg kg-1 dry weight.  相似文献   

19.
The concentration of the histamine metabolite 1-methylimidazole-4-acetic acid was determined in brain tissue from rat and mouse with a gas chromatographic-mass spectrometric method. Mouse brain contained 1.7-3.2 nmol/g, depending on the strain. The concentration in cerebrum from Sprague-Dawley rats was 1.2 nmol/g, whereas cerebellum contained 0.24 nmol/g. The concentration of tele-methylhistamine in mouse brain was 1.4-2.2 nmol/g. The concentration of 1-methylimidazole-4-acetic acid in rat brain after death did not change significantly during 2 h at room temperature.  相似文献   

20.
The influence of MX(3-Chloro-4(Dichloromethyl)-5-Hydroxy-2(5H)- Furanone), a stronglymutagenic compound, on the temperature dependence of the dcelectrical conductivity of collagen as a function of time was studied.Collagen was immersed in MX solution, next dried and pressed intotablets. The MX concentration was measured by HPLC analysis.The reduction of MX concentration to 10% of the initial value wasobserved in the presence of collagen in the solution, whereas in thecontrol solution concentration of MX decreased to 70% of the initialvalue. Measurements of electrical conductivity were performed for thetemperature range 295–453K and activation energies for the chargeconduction process were calculated. Within the temperature range295–340K, the presence of MX decreased electrical conductivity ofcollagen. Calculated activation energies were typical for dry proteins.Within the temperature range 295–320K activation energy decreasedwith time, probably due to the stronger interactions in thecollagen-water-MX system. For temperatures between 320–410 and430–450K the activation energy was not time dependent and theapplication of MX did not change the structure of the collagenmacromolecule. The temporary changes occurring at the lowertemperatures being due solely to changes in the collagen-waterinteractions.  相似文献   

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