The mode of action of homocysteine on mouse brain glutamic decarboxylase and γ-aminobutyrate aminotransferase

1977 ◽  
Vol 55 (9) ◽  
pp. 1013-1018 ◽  
Author(s):  
G. Tunnicliff ◽  
T. T. Ngo
Keyword(s):  
Amino Acid ◽  
Mouse Brain ◽  
Mode Of Action ◽  
Acid Metabolism ◽  
Competitive Inhibition ◽  
The Other ◽  
Aminobutyric Acid ◽  
Aminobutyrate Aminotransferase ◽  
Dual Action

In the belief that homocysteine-induced convulsions might be related to alterations in brain γ-aminobutyric acid metabolism, we have studied the action of this amino acid on the activity of glutamic decarboxylase (GAD, EC 4.1.1.15) and γ-aminobutyrate aminotransferase (EC 2.6.1.19)of mouse brain in vitro. DL-homocysteine competitively inhibited GAD with respect to both L-glutamate and pyridoxal 5′-phosphate. The respective Ki's were 3.8 mM and 0.3 mM, The activity of GABA-T also was altered in the presence of DL-homocysteine. A competitive inhibition (Ki = 6 mM) was observed with γ-aminobutyric acid, and an uncompetitive inhibition with respect to pyridoxal 5′-phosphate and α-ketoglutarate. These results are explained in terms of a dual action of homocysteine on each of the enzymes: one involving a competition for substrate binding site and the other involving the formation of an inactive inhibitor – cofactor complex. The significance of the inhibition of these enzymes of γ-aminobutyric acid metabolism is discussed in relation to the convulsant action of homocysteine.

The effect of polyamines on the enzymes of the 4-aminobutyric acid metabolism in mouse brain in vitro

FEBS Letters ◽  
1980 ◽  
Vol 112 (2) ◽  
pp. 289-292 ◽  
Author(s):  
S.P. Lapinjoki ◽  
A.E.I. Pajunen ◽  
O.A. Hietala ◽  
R.S. Piha
Keyword(s):  
Mouse Brain ◽  
Acid Metabolism ◽  
Aminobutyric Acid

Oxytocin analogues with non-coded amino acid residues in position 8: [8-Neopentylglycine]oxytocin and [8-cycloleucine]oxytocin

1987 ◽  
Vol 52 (9) ◽  
pp. 2317-2325 ◽  
Author(s):  
Jan Hlaváček ◽  
Jan Pospíšek ◽  
Jiřina Slaninová ◽  
Walter Y. Chan ◽  
Victor J. Hruby
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
The Other ◽  
Amino Acid Residues ◽  
Phase Synthesis ◽  
Other Hand ◽  
Fragment Condensation

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

scholarly journals Uptake and Metabolism of Tritiated 17ß-Oestradiol and Oestrone by Rabbit Uterine Tissue in vitro

1974 ◽  
Vol 27 (2) ◽  
pp. 137 ◽  
Author(s):  
RG Gabb ◽  
GM Stone
Keyword(s):  
Nuclear Receptor ◽  
Mode Of Action ◽  
Nuclear Extract ◽  
Lower Proportion ◽  
The Other ◽  
Uterine Tissue ◽  
Uptake And Metabolism

To determine whether the established capability of rabbit uterine tissue to interconvert 17 p-oestradiol and oestrone might have some effect on the mode of action of the oestrogens in this organ, the in vitro interconversion of [3H]-17p-oestradiol and [3H]oestrone by rabbit endometrial and myometrial tissue was investigated and the identity of radiometabolites in 'soluble, 'mitochondrial-microsomal' a'nd 'nuclear' preparations was studied. Both endometrial and myometrial tissue were found to be capable of oxidoreduction of the oestrogens, the equilibrium of the reaction favouring the reduction of oestrone. Irrespective of the tissue--steroid combination studied, the greater part of the radioactivity in all fractions was associated with 17p-oestradiol. The relative proportions of [3Hl-17p-oestradiol and [3H]oestrone varied between fractions, the nuclear preparation consistently showing a lower proportion of oestrone than the other fractions. Sephade<c fractionation of a 0'4M KCl 'nuclear extract' revealed that proportionately less oestrone than 17p-oestradiol was bound to the nuclear 'receptor'. These findings provide further evidence for 17p-oestradiol being the ovarian oestrogen which is active in the uterus, and suggest a role for uterine oxidoreduction of oestrogens in the control exercised over this organ by these steroids.

scholarly journals Metabolic profile of in vitro derived human embryos is not affected by the mode of fertilization

2020 ◽  
Vol 26 (4) ◽  
pp. 277-287
Author(s):  
Christine Leary ◽  
Roger G Sturmey
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Metabolic Profile ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Human Embryos ◽  
Embryo Morphology ◽  
Male Factor ◽  
Triglyceride Content

Abstract The pattern of metabolism by early embryos in vitro has been linked to a range of phenotypes, including viability. However, the extent to which metabolic function of embryos is modified by specific methods used during ART has yet to be fully described. This study has sought to determine if the mode of fertilization used to create embryos affects subsequent embryo metabolism of substrates. A metabolic profile, including consumption of key substrates and the endogenous triglyceride content of individual IVF and ICSI supernumerary embryos, was assessed and compared. Embryo development and quality was also recorded. All embryos were donated at a single clinical IVF center, on Day 5, from 36 patients aged 18–38 years, The data revealed that consumption of glucose and pyruvate, and production of lactate, did not differ between embryos created by IVF or ICSI. Similarly, the mode of insemination did not impact on the triglyceride content of embryos. However, ICSI-derived embryos displayed a more active turnover of amino acids (P = 0.023), compared to IVF embryos. The specific amino acids produced in higher quantities from ICSI compared to IVF embryos were aspartate (P = 0.016), asparagine (P = 0.04), histidine (P = 0.021) and threonine (P = 0.009) while leucine consumption was significantly lower (P = 0.04). However, importantly neither individual nor collective differences in amino acid metabolism were apparent for sibling oocytes subjected to either mode of fertilization. Embryo morphology (the number of top grade embryos) and development (proportion reaching the blastocyst stage) were comparable in patients undergoing IVF and ICSI. In conclusion, the microinjection of spermatozoa into oocytes does not appear to have an impact on subsequent metabolism and viability. Observed differences in amino acid metabolism may be attributed to male factor infertility of the patients rather than the ICSI procedure per se.

Amino acid metabolism of bovine blastocysts derived from parthenogenetically activated or in vitro fertilized oocytes

1998 ◽  
Vol 10 (3) ◽  
pp. 279 ◽  
Author(s):  
Y. G. Jung ◽  
T. Sakata ◽  
E. S. Lee ◽  
Y. Fukui
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Culture Medium ◽  
Acid Metabolism ◽  
Essential Amino Acids ◽  
Fluid Medium ◽  
Vitro Fertilization ◽  
Oviduct Fluid

The uptake and synthesis of 19 amino acids by fresh or frozen–thawed bovine blastocysts produced by parthenogenesis (PT) or in vitro fertilization (IVF) were compared in the present study. Fresh blastocysts, 180 h after IVF or PT activation, and frozen–thawed blastocysts, 168 h old and cultured for 12 h post-thawing, were cultured in synthetic oviduct fluid medium (SOFM) containing polyvinyl alcohol (PVA) with both essential and non-essential amino acids (EAA and NEAA, respectively) (Medium 1: M1) or SOFM containing PVA with only EAA (Medium 2: M2). In Experiment 1, when fresh or frozen–thawed PT blastocysts were cultured in M1, the uptake of glutamate (in fresh only), aspartate and arginine, and the synthesis of glutamine and alanine were significantly enhanced. In the culture with M2, serine, asparagine, glutamate, glutamine, glycine, arginine and alanine were significantly taken up. It was found that the glutamine concentrations was significantly higher (P < 0.001) in the culture medium drops containing embryos than in the drops without embryos. In Experiment 2, when PT blastocysts were cultured in M1, the uptake of aspartate and synthesis of alanine were greater (P < 0.01) than those by IVF blastocysts. When M2 was used, a significant (P < 0.01) production of serine, asparagine, glutamate, glutamine and alanine, and the uptake of arginine by PT blastocysts were observed. In Experiment 3, when IVF blastocysts were cultured in M1, fresh blastocysts depleted more aspartate and glutamate, and produced more glutamine and alanine than frozen–thawed blastocysts. When cultured in M2, frozen–thawed blastocysts depleted more threonine (P < 0.01) than fresh blastocysts. These results indicate that the uptake and synthesis of amino acids were different in fresh or frozen–thawed bovine blastocysts derived from PT or IVF. These differences in amino acid metabolism may be related to the viability of the blastocysts.

Two distinct inhibitory responses of cultured, mammalian spinal neurones to ibotenic acid

1980 ◽  
Vol 58 (9) ◽  
pp. 1135-1137 ◽  
Author(s):  
John Ferguson MacDonald ◽  
Jeffery L. Barker
Keyword(s):  
Amino Acid ◽  
Input Resistance ◽  
Ibotenic Acid ◽  
The Other ◽  
Aminobutyric Acid ◽  
Ionic Mechanism ◽  
Structural Analogue ◽  
Membrane Hyperpolarization ◽  
Excitatory Response ◽  
Spinal Neurones

Ibotenic acid, a structural analogue of glutamic acid, was applied to mouse spinal neurones grown in dissociated cultures. This amino acid evoked two inhibitory responses in addition to an excitatory response. Both inhibitory responses were manifested by membrane hyperpolarization and decreased input resistance. However, one was long-lasting (in excess of periods of 1 h) in comparison with the other. The latter response was likely a consequence of an increased chloride conductance and was sensitive to the γ-aminobutyric acid antagonists bicuculline and picrotoxin whereas the former response was insensitive to these drugs. The ionic mechanism of this long-lasting response has yet to be elucidated.

scholarly journals Termination-altering mutations in the second-largest subunit of yeast RNA polymerase III.

1995 ◽  
Vol 15 (3) ◽  
pp. 1467-1478 ◽  
Author(s):  
S A Shaaban ◽  
B M Krupp ◽  
B D Hall
Keyword(s):  
Amino Acid ◽  
Rna Polymerase ◽  
Transcription Initiation ◽  
Transcription Termination ◽  
Rna Polymerase Iii ◽  
In Vitro Transcription ◽  
The Other ◽  
Polymerase Iii

In order to identify catalytically important amino acid changes within the second-largest subunit of yeast RNA polymerase III, we mutagenized selected regions of its gene (RET1) and devised in vivo assays for both increased and decreased transcription termination by this enzyme. Using as the reporter gene a mutant SUP4-o tRNA gene that in one case terminates prematurely and in the other case fails to terminate, we screened mutagenized RET1 libraries for reduced and increased transcription termination, respectively. The gain in suppression phenotype was in both cases scored as a reduction in the accumulation of red pigment in yeast strains harboring the ade2-1 ochre mutation. Termination-altering mutations were obtained in regions of the RET1 gene encoding amino acids 300 to 325, 455 to 486, 487 to 521, and 1061 to 1082 of the protein. In degree of amino acid sequence conservation, these range from highly variable in the first to highly conserved in the last two regions. Residues 300 to 325 yielded mainly reduced-termination mutants, while in region 1061 to 1082, increased-termination mutants were obtained exclusively. All mutants recovered, while causing gain of suppression with one SUP4 allele, brought about a reduction in suppression with the other allele, thus confirming that the phenotype is due to altered termination rather than an elevated level of transcription initiation. In vitro transcription reactions performed with extracts from several strong mutants demonstrated that the mutant polymerases respond to RNA terminator sequences in a manner that matches their in vivo termination phenotypes.

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