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91.
J. Garforth J. H. McKie R. Jaouhari T. J. Benson A. H. Fairlamb K. T. Douglas 《Amino acids》1994,6(3):295-299
Summary The rational design of ligands for the substrate-binding site of a homology-modelled trypanothione reductase (TR) was performed. Peptides were designed to be selective for TR over human glutathione reductase (GR). The design process capitalized on the proposed differences between the activesites of TR and human GR, subsequently confirmed by the TR crystal structure. Enzyme kinetics confirmed that forT. cruzi TR benzoyl-Leu-Arg-Arg-ß-naphthylamide was an inhibitor (Ki 13.8µM) linearly competitive with the native substrate, trypanothione disulphide, and did not inhibit glutathione reductase. 相似文献
92.
Summary The kinetics of putrescine and spermidine uptake and the influence of calcium on the kinetic parameters of the transport process were investigated in protoplasts isolated from carrot phloem parenchyma. Spermidine uptake dependence on external concentration was biphasic, both in the absence and in the presence of 1 mM CaCl2. In the first case, saturation was reached at 0.1 to 0.25 mM and the Km value was 43µM. When calcium was added, the Km and Vmax increased. A similar pattern was found with regard to putrescine uptake. Moreover, in order to clarify the mode of action of calcium on polyamine uptake, lanthanides (lanthanum and gadolinium) were utilised as Ca+2-channel antagonists. When protoplasts were preincubated with these lanthanides, the stimulatory effect exerted by Ca+2 on polyamine uptake was almost totally abolished. On the other hand, if lanthanum was supplied instead of calcium, it gave rise to a small enhancement of polyamine transport. These results induce us to suggest that calcium acts on polyamine uptake both by binding to external sites on the plasmalemma and by penetrating into the cell. 相似文献
93.
Summary Although the regulatory activity of steroid hormones on amino acid metabolism has been described, no information is published on the effect of ovariectomy. We studied the influence of ovariectomy in Wistar rats determining the amino acids phenylalanine and tyrosine in liver, kidney, plasma and urine. 32 animals were used in the study, 12 animals were sham operated, 9 animals were ovariectomized and 11 rats were ovariectomized and supplemented with estradiol. No quantitative changes were detected comparing liver and kidney phenylalanine and tyrosine between the groups (sham operated rats liver phenylalanine 2,53nM/mg ± 1,07; liver tyrosine 1.95nM/mg ± 0.92; kidney phenylalanine 2.16nM/mg ± 0.53; kidney tyrosine 1.80nM/mg ± 0.39. Ovariectomized rats showed liver phenylalanine 3.07nM/mg ± 1.14; liver tyrosine 2.63nM/mg ± 1.01; kidney phenylalanine 2.30 nM/mg ± 0.74; kidney tyrosine 1.93nM/mg ± 0.63. Ovariectomized and estradiol supplemented rats presented with liver phenylalanine 2.84nM/mg ± 1.40; liver tyrosine 2.35nM/mg ± 1.28; kidney phenylalanine 1.91nM/mg ± 0.26, kidney tyrosine 1.67nM/mg ± 0.23.). When, however, the phenylalanine/tyrosine ratio in the liver was evaluated, ovariectomized rats showed a significant decrease of the quotient (p = 0.001). The phenylalanine/tyrosine ratio was restored by estradiol replacement. Our findings show that phenylalanine and tyrosine metabolism is under estradiol control. The effect on the metabolic changes could be mediated by enzyme systems as phenylalanine hydroxylase, tyrosine hydroxylase and tyrosine aminotransferase. Our results would be compatible with previous reports on the stimulatory effect of estradiol on these enzymes. The kidney phenylalanine/tyrosine ratio was unaffected by ovariectomy and/or estradiol replacement which can be easily explained by different pools, enzyme activities, filtration/reabsorption effects, etc.The urinary P/T ratio was decreased by ovariectomy and restored by estradiol replacement indicating endocrine control of renal reabsorption and secretion mechanisms. 相似文献
94.
Summary Total D-amino acids were measured in plasma for 20 non-dialysed patients (creatinine clearance < 12 ml/minute), 20 on CAPD, 20 on haemodialysis and 20 normals. Plasma D-tyrosine and D-phenylalanine were measured in 8 of each group by HPLC. Total D-amino acids, D-tyrosine and D-phenylalanine were significantly greater for patients than normals. D-amino acids and D-tyrosine correlated with creatinine and were decreased during HD. During dialysis, the mean losses for D-tyrosine and D-phenylalanine were similar, about 0.2 mg/CAPD exchange and 3 mg/4 hour haemodialysis (i.e. 2% of the total amino acid, as in plasma). Clearance was unaffected by stereochemical configuration. Urinary losses/24 hour in the non-dialysed patients were 0.35 mg D-tyrosine and 0.25 mg D-phenylalanine. Clearance for D-phenylalanine was greater than for the L-enantiomer. Increases in D-amino acids in renal failure are probably due to depletion of D-amino acid oxidase, but may be enhanced by a D-amino acid rich diet, peptide antibiotics and D-amino acid oxidase inhibiting drugs and metabolites. Possible toxic effects need further investigation. 相似文献
95.
Summary The structure-activity data of 6 years on 395 analogs of the luteinizing hormone releasing hormone (LHRH) have been studied to determine effective substituents for the ten positions for maximal antiovulatory activity and minimal histamine release. The numbers of substituents studied in the ten positions are as follows: (41)1-(12)2-(12)3-(5)4-(47)5-(52)6-(16)7-(18)8-(4)9-(8)10. In position 1, DNal and DQal were effective with the former being more frequently the better substituent. DpClPhe was uniquely effective in position 2. Positions 3 and 4 are very sensitive to change. D3Pal in position 3 and Ser in position 4 of LHRH were in the best antagonists. PicLys and cPzACAla were the most successful residues in position 5 with cPzACAla being the better substituent. Position 6 was the most flexible and many substituents were effective; particularly DPicLys. Leu7 was most often present in the best antagonists. In position 8, Arg was effective for both antiovulatory activity and histamine release; ILys was effective for potency and lesser histamine release. Pro9 of LHRH was retained. DAlaNH2
10 was in the best antagonists.Abbreviations AABLys
N
-(4-acetylaminobenzoyl)lysine
- AALys
N
-anisinoyl-lysine
- AAPhe
3-(4-acetylaminophenyl)lysine
- Abu
2-aminobutyric acid
- ACLys
N
-(6-aminocaproyl)lysine
- ACyh
1-aminocyclohexanecarboxylic acid
- ACyp
1-aminocyclopentanecarboxylic acid
- Aile
alloisoleucine
- AnGlu
4-(4-methoxy-phenylcarbamoyl)-2-aminobutyric acid
- 2ANic
2-aminonicotinic acid
- 6ANic
6-aminonicotinic acid
- APic
6-aminopicolinic acid
- APh
4-aminobenzoic acid
- APhe
4-aminophynylalanine
- APz
3-amino-2-pyrazinecarboxylic acid
- Aze
azetidine-2-carboxylic acid
- Bim
5-benzimidazolecarboxylic acid
- BzLys
N
-benzoyllysine
- Cit
citrulline
- Cl2Phe
3-(3,4-dichlorphenyl)alanine
- cPzACAla
cis-3-(4-pyrazinylcarbonylaminocyclohexyl)alnine
- cPmACAla
cis-3-[4-(4-pyrimidylcarbonyl)aminocyclohexyl]alanine
- Dbf
3-(2-dibenzofuranyl)alanine
- DMGLys
N
-(N,N-dimethylglycyl)lysine
- Dpo
N
-(4,6-dimethyl-2-pyrimidyl)-ornithine
- F2Ala
3,3-difluoroalanine
- hNal
4-(2-naphthyl)-2-aminobutyric acid
- HOBLys
N
-(4-hydroxybenzoyl)lysine
- hpClPhe
4-(4-chlorophenyl)-2-amino-butyric acid
- Hse
homoserine, 2-amino-4-hydroxybutanoic acid
- ICapLys
N
-(6-isopropylaminocaproyl)lysine
- ILys
N
-isopropyllysine
- Ind
indoline-2-carboxylic acid
- INicLys
N
-isonicotinoyllysine
- IOrn
N
-isopropylornithine
- Me3Arg
NG,NG,NG-trimethylarginine
- Me2Lys
N
,N
-dimethyllysine
- MNal
3-[(6-methyl)-2-naphtyl]alanine
- MNicLys
N
-(6-methylpicolinoyl)lysine
- MPicLys
N
-(6-methylpicolinoyl)lysine
- MOB
4-methoxybenzoyl
- MpClPhe
N-methyl-3-(4-chlorphenyl)lysine
- MPZGlu
glutamic acid,-4-methylpiperazine
- Nal
3-(2-naphthyl)alanine
- Nap
2-naphthoic acid
- NicLys
N
-nicotinoyllysine
- NO2B
4-nitrobenzoyl
- NO2Phe
3-(4-nitrophenyl)alanine
- oClPhe
3-(2-chlorphenyl)alanine
- Opt
O-phenyl-tyrosine
- Pal
3-(3-pyridyl)alanine
- 2Pal
3-(2-pyridyl)alanine
- 2PALys
N
-(3-pyridylacetyl)lysine
- pCapLys
N
-(6-picolinoylaminocaproyl)lysine
- pClPhe
3-(4-chlorophenyl)alanine
- pFPhe
3-(4-fluorophenyl)-alanine
- Pic
picolinic acid
- PicLys
N
-picolinoyllysine
- Pip
piperidine-2-car-boxylic acid
- PmcLys
N
-(4-pyrimidylcarbonyl)lysine
- Ptf
3-(4-trifluromethyl phenyl)alanine
- Pz
pyrazinecarboxylic acid
- PzAla
3-pyrazinylalanine
- PzAPhe
3-(4-pyrazinylcarbonylaminophenyl)alanine
- Qal
3-(3-quinolyl)alanine
- Qnd-Lys
N
-quinaldoyllysine
- Qui
3-quinolinecarboxylic acid
- Qux
2-quinoxalinecarboxylic acid
- Tic
1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
- TinGly
2-thienylglycine
- tNACAla
trans-3-(4-nicotinoylaminocyclohexyl)-alanine
- tPACAla
trans-3-(4-picolinoylaminocyclohexyl)alanine 相似文献
96.
Summary The chirospecific conversions of D-glucosamine hydrochloride and D-mannosamine hydrochloride to the configurationally stable L and D isomers of N-t-butyloxycarbonylserinal were carried out byt-butylcarbonylation followed by sodium borohydride reduction and sodium meta-periodate oxidation. Reaction of the L and D aldehydes with the Wittig reagent prepared from 4-chlorobenzyltriphenylphosphonium chloride and butyl lithium followed by catalytic hydrogenation, Jones oxidation and salt formation with dicyclohexylamine gave the DCHA salts of the D and L isomers ofp-chlorohomophenylalanine N-t-Boc in high enatiomeric excess. The optical purity of the title compounds was established by hydrolysis to the respective free amino acids, followed by chiral derivatization and HPLC analysis.This was presented at the Fifth International Kyoto Conference on new Aspects of Organic Chemistry, Kyoto, Japan, November 11–15, 1991. Abstract #GO-13. 相似文献
97.
Summary The lipophilicity (or hydrophobicity) of amino acids is an important property relevant for protein folding and therefore of great interest in protein engineering. For peptides or peptidomimetics of potential therapeutic interest, lipophilicity is related to absorption and distribution, and thus indirectly relates to their bioactivity. A rationalization of peptide lipophilicity requires basic knowledge of the lipophilicity of the constituting amino acids. In the present contribution we will review methods to measure or calculate the lipophilicities of amino acids, including unusual amino acids, and we will make a comparison between various lipophilicity scales. 相似文献
98.
Effect of essential fatty acids on circulating T cell subsets in patients with colorectal cancer 总被引:2,自引:0,他引:2
P. Purasiri J. Ashby S. D. Heys O. Eremin 《Cancer immunology, immunotherapy : CII》1994,39(4):217-222
The effect of essential fatty acids (EFA), given orally as dietary supplements, on the responsiveness in vitro of peripheral blood lymphocytes (PBL), to the mitogen concanavalin A have been studied in 10 patients with localized and 14 patients with advanced colorectal cancer. The degree of lymphocyte activation was assessed by measuring the amount of tritiated [3H]thymidine incorporated into newly synthesised lymphocyte DNA. The results were expressed as stimulation indices. T cell responses to concanavalin A stimulation showed a significant reduction of stimulation indices following EFA supplementation, in both the localized (P=0.026) and advanced (P=0.016) tumour groups, when compared with pretreatment activity in vitro. Mixing experiments, using EFA-supplemented and non-EFA-supplemented lymphocytes with concanavalin A, suggest no enhancement of T suppressor cell activity. Cell surface marker analysis (fluorescence-activated cell sorting for CD phenotyping) revealed a reduction of absolute numbers of CD4+ and CD8+ lymphocytes following EFA supplementation. The stimulation indices returned to presupplementation values 3 months following cessation of EFA intake. There was no significant change of these indices in the control (no EFA supplementation) advanced tumour group tested. This study suggests that EFA supplementation in patients with colorectal cancer selectively reduces circulating PBL. and T cell subset (including suppressor cells) numbers and/or activity. Such effects may have an important outcome in patients with malignant disease.This work was supported by grants from the Grampian Health Broad, the Royal College of Surgeons of Edinburgh, and Scottish Hospital Endownment Research Trust 相似文献
99.
We examined the dose response, time course and reversibility of the effect of methyl 2-tetradecylglycidate (McN-3716, methyl palmoxirate or MEP), an inhibitor of -oxidation of fatty acids, on incorporation of radiolabeled palmitic acid ([U-14C]PA) from plasma into brain lipids of awake rats. MEP (0.1, 1 and 10 mg/kg) or vehicle was administered intravenously from 10 min to 72 hr prior to infusion of [U-14C]PA. Two hr pretreatment with MEP (0.1 to 10 mg/kg) increased brain organic radioactivity 1.2 to 1.8 fold and decreased brain aqueous radioactivity by 1.2 to 3.0 fold when compared to control values. At 10 mg/kg, MEP significantly increased brain organic fraction from 40% in controls to 85%, 30 min to 6 hr pretreatment, and resulted in a redistribution of the radiolabeled fatty acid toward triacylglycerol. MEP changed the lipid/aqueous brain ratio of incorporated [U-14C]PA from 0.67 to 5.7. The incorporation rate coefficient, k*, was significantly increased by MEP (10 mg/kg) at 2 hr (31%), 4 hr (59%) and 6 hr (34%). All effects were reversed by 72 hr, consistent with a half-life of 2 days for carnitine palmitoyl transferase I. These results indicate that intravenous MEP may be used with [1-11C]palmitic acid for studying brain lipid metabolism in vivo by positron emission tomography, as it significantly reduces the large unincorporated aqueous fraction that would result in high background radioactivity. 相似文献
100.
Monosodium glutamate (MSG) is added to many processed foods at significant levels for flavor enhancement. It is also naturally occurring at high levels in some foods. The enantiomeric composition of free glutamate in foods was examined and all foods analyzed were found to contain D -glutamate. The relative percent of D -glutamate in the food products studied depended on the origin of the glutamate. Foods to which MSG was added by the manufacturer had a high total level of MSG but a lower relative percentage of the D -enantiomer (usually less than 0.8%). In comparison, fermented foods tend to have high relative levels of D -glutamate but a lower total amount of the amino acid. The relative percent of D -glutamate in nonfermented foods containing no added MSG was also found to be low compared to fermented products. In some cases the percent D -glutamate could be related to the relative amounts of other food ingredients such as cheese. © 1994 Wiley-Liss, Inc. 相似文献