Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GLYCINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes.

1. Glycine responses were studied under voltage clamp in Xenopus oocytes injected with cDNA encoding mammalian glycine receptor subunits and in rat medullary neurones. Bath application of glycine gave strychnine-sensitive currents which reversed close to the expected equilibrium potentials for chloride ions. The peak currents for the receptors expressed in oocytes fitted a Hill equation with EC50 = 215 +/- 5 microM and Hill coefficient nH = 1.70 +/- 0.05 (means +/- s.e. means). The peak currents from the receptors in medullary neurones fitted a Hill equation with EC50 = 30 +/- 1 microM and Hill coefficient nH = 1.76 +/- 0.08. The current-voltage relationship for the receptors expressed in oocytes showed strong outward rectification (with Vrev = -21 +/- 2 mV), while that for the glycine responses from the medullary neurones in symmetrical Cl- was linear (with Vrev = 3.2 +/- 0.6 mV). 2. Inhalational general anaesthetics, at concentrations close to their human minimum alveolar concentrations (MACs), potentiated responses to low concentrations of glycine. The potentiation observed with the recombinant receptors (between 60-22%) was approximately twice that found with the medullary neurones (between 40-80%). For both the recombinant receptors and the receptors in medullary neurones, the degree of potentiation increased in the order of methoxyflurane approximately sevoflurane < halothane approximately isoflurane approximately enflurane. There was no significant difference between the potentiations observed for the two optical isomers of isoflurane. 3. For both the recombinant and native receptors, isoflurane potentiated the currents in a dose-dependent manner at low concentrations of glycine, although at high glycine concentrations the anaesthetic had no significant effect on the glycine-activated responses. The major effect of isoflurane was to cause a parallel leftward shift in the glycine concentration-response curves. The glycine EC50 concentration for the recombinant receptors decreased from a control value of 215 +/- 5 microM to 84 +/- 7 microM glycine at 610 microM isoflurane, while that for the medullary neurones decreased from a control value of 30 +/- 1 microM to 18 +/- 2 microM glycine at the same concentration of isoflurane. The potentiation was independent of membrane potential. 4. Isoflurane also potentiated responses to taurine, a partial agonist at the glycine receptor. This was observed for receptors expressed in oocytes at both low and saturating concentrations of taurine. The EC50 concentration decreased from a control value of 1.6 +/- 0.2 to 0.9 +/- 0.1 mM taurine in the presence of 305 microM isoflurane, while the maximum response to taurine increased from 47 +/- 2 to 59 +/- 2% of the maximum response to glycine. 5. Glycine receptors, like other members of the fast ligand-gated receptor superfamily, are sensitive to clinically relevant concentrations of inhalational general anaesthetics. Effects at these receptors may, therefore, play some role in the maintenance of the anaesthetic state.

Administration, Inhalation↗
PubMed2002

Effect of glycine on the cell yield and growth rate of Escherichia coli: evidence for cell-density-dependent glycine degradation as determined by (13)C NMR spectroscopy.

Addition of selected amino acids could be a means to improve production of recombinant proteins in industrial processes. We found that glycine increased the maximum specific growth rate of Escherichia coli from 0.67 to 0.78 h(-1), and the cell yield from 0.57 to 0.98 g dry weight per g substrate, when supplemented to batch cultures in a glucose-mineral medium. Maximum effect occurred at pH 6.8, at a glycine concentration of 6-12 mmol l(-1), and at cell densities below 1.15 g dry weight l(-1) (0D(610).3). When glycine was added to a culture at a cell density of 1.15 g l(-1) or above, no growth promoting effect of glycine was seen. The 'glycine effect' was not due to CO(2) produced by the glycine cleavage system (GCV), and the lack of effect at higher cell densities was not masked by acetate accumulation, but coincided with increased acetate production. The metabolism of glycine was further investigated in cultures supplied with [2-(13)C] labelled glycine, and the redistribution of label in the [1-(13)C], [2-(13)C], and [1,2-(13)C] isotopomeres of excreted acetate was analysed by 13C NMR. The NMR data revealed that very little degradation of glycine occurred at cell densities below 1.15 g l(-1). Simultaneously the biosynthesis of serine and glycine was repressed as judged by the absence of [2-(13)C] acetate, implying that added glycine was used as a source of glycine, serine, one-carbon units, and threonine. At cell densities above 1.15 g l(-1), 53% of the consumed glycine carbon was excreted as acetate. Degradation of glycine was associated with an increased uptake rate, cleavage by GCV, and degradation of both glycine-derived serine, and glucose-derived serine to pyruvate. This switch in metabolism appears to be regulated by quorum sensing.

Acetic Acid↗
PubMed1991

Glycine transport by human red blood cells and ghosts: evidence for glycine anion and proton cotransport by band 3.

Stilbene-sensitive glycine transport was investigated in human red blood cells and ghosts. We have found that this component of glycine transport was inhibited by the stilbene derivatives 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS); the apparent constant for inhibition by DNDS was 4 microM in the presence of 150 mM chloride. DNDS-sensitive glycine influx was modulated by pH such that as pH was increased from 5.9 to 9.2, transport increased from 2.5 to 140 mumol.kg Hb-1.h-1 at 37 degrees C and 100 microM glycine. The increased transport was correlated with an increase in the amount of glycine present as the anion over this pH range (0.03-40 microM glycine anion), but, in addition, pH had a direct effect on transport. Glycine influx was studied as a function of glycine anion concentration with anion varied by changing pH at a constant total glycine concentration and by changing total glycine at a constant pH. A comparison of these data demonstrated that the stilbene-sensitive glycine anion flux is stimulated by protons with half-maximal stimulation below pH 6.5 and suggests that the glycine anion and a proton are cotransported. Inorganic anions transported by band 3, including Cl, NO3, and SO4, inhibited glycine transport. Glycine flux into resealed ghosts was inhibited by Cl with an inhibition constant of 25 mM. The similarities between the kinetic constants for transport inhibition by Cl and DNDS and the kinetic constants for Cl and DNDS binding to band 3 suggest that the DNDS-sensitive glycine anion and proton cotransport is via band 3.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Glycine and glycine receptor immunoreactivity in brain and spinal cord.

To study the distribution of glycine immunoreactive neurons in the spinal cord and brain, antisera were raised against glycine conjugated to protein carriers. High-titer rabbit glycine antiserum was purified by affinity chromatography. Testing against other amino acids and peptides with immuno dot blots and ELISA assays showed little apparent cross-reaction with glutamate, aspartate, glutamine, taurine, and 17 other amino acids and related compounds. Similarly, the antiserum showed little apparent recognition of glycine when glycine was incorporated into peptides. A slight cross-reactivity with GABA, beta-alanine, and cysteine was found. Immunocytochemical labeling of tissue sections could be blocked with glycine conjugated to a heterologous carrier protein but not by other amino acids conjugated to that protein. Immunocytochemistry at the light microscope level with immunofluorescence and silver-intensified colloidal gold revealed a wide distribution of glycine-like immunoreactivity throughout all laminae of the rat spinal cord and in all segments studied from the cervical, thoracic, lumbar, and sacral cord. Immunoreactive boutons were found terminating on both cell bodies and on dendrites. Ultrastructural analysis with postembedding colloidal gold immunocytochemistry demonstrated large numbers of immunoreactive boutons making symmetrical type synapses with neuronal perikarya, including motor neurons, and with proximal and distal dendrites. Presynaptic glycine immunoreactive boutons were found in both ventral and dorsal horn. Immunoreactivity was concentrated over regions rich in vesicles, and over mitochondria in immunoreactive boutons, but not over mitochondria in postsynaptic dendrites. Glycine-immunoreactive perikarya were identified both in the dorsal horn and in the ventral horn. Myelinated and unmyelinated glycine-immunoreactive axons were noted both in the gray and white matter of the cord. The density of immunoreactive axons varied in the white matter, with the greatest number of immunoreactive axons found in the white matter adjacent to the gray matter in lateral and ventral white. Significantly fewer immunoreactive axons were found in the white matter of the dorsal columns. Myelin sheaths around axons were unlabeled. The distribution of glycine-immunoreactive boutons correlated well with the distribution of glycine receptor immunoreactivity on postsynaptic elements of the spinal cord, tested with different monoclonal antisera against strychnine-purified glycine receptor. Glycine receptor immunoreactivity was found throughout the gray matter of both rat and primate.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Enrichment of glycine pool in plasma and tissues by glycine, di-, tri-, and tetraglycine.

Very little information is available on metabolism of oligopeptides in vivo. The present studies were performed to investigate the metabolic fate of diglycine, triglycine, and tetraglycine when injected into a central vein in rats. These peptides disappeared rapidly from plasma without any significant loss in urine. Plasma and tissue concentrations of glycine were measured when the same amount of glycine was injected in free or peptide form. Two minutes after the injection of glycine (1.l0 mumol/g body wt), there was over a tenfold increase in plasma glycine concentration. This increase was diminished when diglycine instead of glycine was injected. Each increase in the number of glycine residues resulted in further reduction in the initial rise in plasma glycine concentration was increased by each injection. This was more pronounced in the kidney than in the liver. Injection of triglycine and tetraglycine resulted in greater glycine concentration in the kidney than injection of either glycine or diglycine. Furthermore, unlike liver and muscle, each increase in the number of glycine residues resulted in greater recovery of glycine peptides from the kidney. These results suggest that with each increase in the number of glycine residues a greater amount of injected glycine peptide is taken up by the kidney for hydrolysis to glycine.

Animals↗
PubMed1977

Studies of the glycine cleavage enzyme system in brain from infants with glycine encephalopathy.

Glycine content and enzyme activity of the glycine cleavage system were compared in autopsied brain from five infants dying with glycine encephalopathy and four control infants, including two with other types of hyperglycinemia. Glycine content was elevated 2- to 8-fold and glycine cleavage enzyme activity was undetectable in the brains of the glycine encephalopathy patients. Glycine content and enzyme activity were normal in the brains of the control patients, including one with ketotic hyperglycinemia secondary to methylmalonic acidemia. Prolonged dialysis failed to restore glycine cleavage enzyme activity in brain homogenates of glycine encephalopathy patients, and these homogenates failed to inhibit enzyme activity when added to homogenates of control brain. Radioactive bicarbonate was converted to radioactive glycine by control brain, but not by glycine encephalopathy brain. This finding, together with the results of recombination experiments between solubilized human brain enzymes and purified protein components of the bacterial glycine cleavage system of Arthrobacter globiformis, indicates that the enzyme defect in glycine encephalopathy involves at least the second or H protein of the 4-protein glycine cleavage enzyme system.

Amino Acid Metabolism, Inborn Errors↗
PubMed2001

Pharmacological assessment of the role of the glycine transporter GlyT-1 in mediating high-affinity glycine uptake by rat cerebral cortex and cerebellum synaptosomes.

Two distinct types of glycine transporter, GlyT-1 and GlyT-2, have been characterised. GlyT-1 and GlyT-2 are known to be differentially expressed amongst CNS areas, but direct functional evidence for their relative contributions to high-affinity glycine uptake by brain tissues is lacking. In the present study, we have used the selective GlyT-1 inhibitor N[3-(4"-fluorophenyl)-3-(4"-phenylphenoxy)propyl]sarcosine (NFPS) to investigate the role of GlyT-1 in mediating glycine uptake. HEK293 cells expressing human GlyT-1c or GlyT-2 showed high levels of Na(+)-dependent glycine uptake, with K(m) values of 117+/-13 and 200+/-22 microM, respectively. NFPS potently inhibited uptake in GlyT-1c cells (IC(50) value 0.22+/-0.03 microM), being around 500-fold more potent than glycine or sarcosine, but had no effect on uptake in GlyT-2 cells (IC(50) >10 microM). Efflux of pre-loaded [3H]-glycine from GlyT-1c cells was increased by glycine or sarcosine, whereas NFPS had no effect on its own but blocked the effects of glycine or sarcosine. These results confirm that NFPS is a potent, selective and non-transportable GlyT-1 inhibitor. Rat cortex and cerebellum synaptosomes also showed a high-affinity Na(+)-dependent component of glycine uptake, with affinities similar to those observed for uptake in GlyT-1c or GlyT-2 cells. In cortex synaptosomes, NFPS and sarcosine produced the same maximal inhibition of uptake as glycine itself. However, in cerebellum synaptosomes, the maximal inhibition produced by NFPS and sarcosine was only half that produced by glycine. In both tissues NFPS was around 1000-fold more potent than glycine or sarcosine. Overall, our findings indicate that high-affinity glycine uptake in cerebral cortex occurs predominantly via GlyT-1. However, in cerebellum, only a part of the high-affinity uptake is mediated by GlyT-1, with the remaining NFPS-insensitive component most likely mediated by GlyT-2.

Amino Acid Transport Systems, Neutral↗
PubMed1998

Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses.

Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J. Neurophysiol. 80: 3336-3340, 1998. At central synapses occupation of glycine binding sites of N-methyl--aspartate receptors (NMDA-Rs) is a necessary prerequisite for the excitatory neurotransmitter glutamate to activate these receptors. There is conflicting evidence as to whether glycine binding sites normally are saturated. If they are not, then alterations in local glycine concentration could modulate excitatory synaptic transmission. By using an in vitro brain stem slice preparation we investigated whether the glycine site is saturated for synaptically activated NMDA-Rs in neonatal rat hypoglossal motoneurons. We found that the NMDA-R-mediated component of spontaneous miniature excitatory postsynaptic currents could be potentiated by exogenously applied glycine as well as by -serine. The effects of glycine were observed only at concentrations (100 microM or more) two orders of magnitude above the apparent dissociation constant of glycine from NMDA receptors. In contrast, -serine, a nontransported NMDA-R glycine site agonist, was effective in the low micromolar range, i.e., at concentrations similar to those found to be effective on isolated cells or on outside-out patches. We conclude that at these synapses the glycine concentration around synaptic NMDA-Rs is set below the concentration required to saturate their glycine site and is likely to be stabilized by a powerful glycine transport mechanism.

Animals↗
PubMed1987

Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake.

An antiserum against conjugated glycine was characterized and applied to cerebellar sections of rats and baboons that had been perfusion-fixed with glutaraldehyde. After immunosorbent purification the serum reacted with brain protein-glutaraldehyde-glycine conjugates, but did not stain similar test conjugates prepared from other amino acids, including GABA and beta-alanine. In the rat cerebellum the glycine antiserum selectively labelled a subpopulation of Golgi neurons. Adjacent Vibratome sections treated with an antiserum against conjugated GABA revealed an about equally large subpopulation of immunopositive Golgi cells. A proportion of the Golgi cells that were cleaved by the plane of section contained both immunoreactivities. Additional evidence for a colocalization of glycine and GABA was obtained by postembedding staining of alternate semithin sections with the GABA antiserum and glycine antiserum, respectively. The ability of the antisera to distinguish between fixed glycine and GABA was corroborated by preincubation of the antisera with glutaraldehyde-amino acid fixation complexes: glycine complexes abolished staining with the glycine antiserum but had no effect on the GABA antiserum. The opposite effects were obtained with the GABA complexes. Matching the distributions of the respective immunoreactivities, [3H]glycine uptake was restricted to glomerulus-like structures in the granule cell layer whereas [3H]GABA uptake also occurred in punctate and fibrous profiles in the molecular layer. The baboon showed a distribution of glycine-like immunoreactivity similar to that in the rat, except that a few immunopositive neurons occurred in the molecular layer. The latter neurons were interpreted as outlying Golgi neurons; however, the possibility that they represent a subpopulation of basket cells could not be excluded. The Purkinje cells were negative in both species. Glial cells were weakly stained with the glycine antiserum but were strongly immunopositive after incubation with an antiserum raised against conjugates of the structurally similar amino acid beta-alanine. The present data suggest that glycine and GABA occur in about equally large subpopulations of Golgi neurons. A subpopulation of the Golgi neurons appears to contain both glycine and GABA.

Animals↗
PubMed1976

The effect of feeding various levels of dietary glycine in a pre-experimental diet to one-day old chicks on their subsequent glycine plus serine requirement.

Two experiments were conducted to determine the effect of feeding chicks 1=9 days of age various levels of clycine in corn-casein and corn-soybean-corn gluten meal diets upon the subsequent glycine plus serine requirement of chicks during the remaining 10-21 day feeding period. Chicks in Experiment 1 fed corn-casein basal diets with 1.3% additional dietary glycine (2.15% total glycine plus serine) gained significantly (P less than or equal to 0.01) more weight during an initial 9-day feeding period than chicks fed basal diets with 0.3% and 0.9% supplemental glycine. Chicks fed the 2.15% glycine plus serine diets during the first 9 days posthatching and then fed basal diets containing 0.3% supplemental glycine (1.15% total glycine plus serine) for a 10-21 day feeding period gained weight equivalent to chicks fed 2.15% glycine plus serine diets for the entire 21-day period. The corn-casein basal diet contained 21.0% protein and 0.85% glycine plus serine. Chicks in Experiment 2 fed corn-soybean-corn gluten meal diets containing 1.8% glycine plus serine did not respond to glycine supplementation druing the initial 9-day feeding period or the 10-23 day feeding period. The results suggest feeding optimum levels of glycine to chicks during the first nine days after hatching decreases the requirement of glycine and serine during subsequent feeding periods.

Animal Feed↗
PubMed1995

The Escherichia coli glycine transport system and its role in the regulation of the glycine cleavage enzyme system.

An Escherichia coli K12 mutant defective in both serine biosynthesis (serA) and glycine transport (cycA) was found to exhibit a glycine cleavage negative (GCV-) phenotype, i.e. was unable to use glycine as a serine source. While [2-14C]glycine uptake and induction of a lambda gcvT::lacZ fusion were greatly reduced in a cycA mutant compared to the wild-type, both strains exhibited parallel increases in uptake and induction with increasing exogenous glycine concentrations. A plasmid carrying the wild-type cyc region complemented the GCV- phenotype and restored both glycine uptake and glycine-inducible gcvT::lacZ expression. Wild-type and cycA strains grown in the presence of either a glycine-containing tripeptide or threonine, which can be degraded internally into glycine, exhibited similar induction of the gcvT::lacZ fusion. However, when a gcv mutation, which causes glycine to accumulate within the cell, was introduced into the cycA strain, there was increased induction of the gcvT::lacZ fusion, but induction was less than that observed in a gcv cycA+ strain. It is proposed that cyc serves primarily in the regulation of gcv by transporting glycine into the cell, which endogenously induces gcv expression. However, the possibility of some form of exogenous regulation of gcv, mediated by the cyc-encoded glycine transport system, exists.

Amino Acid Oxidoreductases↗
PubMed1983

Effects of glycine on the crayfish neuromuscular junction. II. Release of inhibitory transmitter activated by glycine.

Glycine applied in the bathing medium at concentrations exceeding 0.1 mol/l elicited high rates of spontaneous inhibitory postsynaptic currents (sIPSCs) in crayfish neuromuscular junctions. This effect of glycine was reversible within seconds. In several experiments on application of 0.5 mol/l glycine the rate of sIPSCs immediately increased to about 10 kHz and thereafter declined exponentially with time constants of between 10 and 20 s. This resulted in a release of about 140,000-200,000 inhibitory quanta per trial. When the readily releasable pool of transmitter had been so depleted by glycine, it was necessary to superfuse the preparation with normal solution for 5-10 min in order to be able to again evoke a high rate of sIPSCs. A similar effect of glycine on spontaneous release was also observed in some preparations which had been previously bathed in zero Ca2+ solution for up to 45 min. Addition of 25 mmol/l Mg2+ to the bathing fluid did not block the glycine evoked release of transmitter. However, in sodium-free superfusions the increase in the rate of sIPSCs induced by glycine was reduced. In the presence of 0.5 mol/l glycine no excitatory miniature currents (sEPSCs) were observed, in fact, glycine depressed excitatory synaptic transmission. In addition to the increasing the rate of sIPSCs, high concentrations of glycine evoked 'giant' sIPSCs (gsIPSCs). They were about 10-15 times larger than the normal sIPSCs and occurred at rates lower than 3 Hz, irrespective of whether the bathing medium contained sodium or not. However, in sodium-free superfusions the time constants of the decay of gsIPSCs were prolonged by a factor 2-3. These results suggest that glycine elicited sIPSCs and gsIPSCs by different mechanisms. Possible mechanisms which might explain the effects of glycine on release of inhibitory transmitter are discussed.

Animals↗
PubMed2001

Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel.

Peptidoglycan polysaccharide (PG-PS) is a primary structural component of bacterial cell walls and causes rheumatoid-like arthritis in rats. Recently, glycine has been shown to be a potential immunomodulator; therefore, the purpose of this study was to determine if glycine would be protective in a PG-PS model of arthritis in vivo. In rats injected with PG-PS intra-articularly, ankle swelling increased 21% in 24 to 48 h and recovered in about 2 weeks. Three days prior to reactivation with PG-PS given intravenously (i.v.), rats were divided into two groups and fed a glycine-containing or nitrogen-balanced control diet. After i.v. PG-PS treatment joint swelling increased 2.1 +/- 0.3 mm in controls but only 1.0 +/- 0.2 mm in rats fed glycine. Infiltration of inflammatory cells, edema, and synovial hyperplasia in the joint were significantly attenuated by dietary glycine. Tumor necrosis factor alpha (TNF-alpha) mRNA was detected in ankle homogenates from rats fed the control diet but not in ankles from rats fed glycine. Moreover, intracellular calcium was increased significantly in splenic macrophages treated with PG-PS; however, glycine blunted the increase about 50%. The inhibitory effect of glycine was reversed by low concentrations of strychnine or chloride-free buffer, and it increased radiolabeled chloride influx nearly fourfold, an effect also inhibited by strychnine. In isolated splenic macrophages, glycine blunted translocation of the p65 subunit of NF-kappaB into the nucleus, superoxide generation, and TNF-alpha production caused by PG-PS. Further, mRNA for the beta subunit of the glycine receptor was detected in splenic macrophages. This work supports the hypothesis that glycine prevents reactive arthritis by blunting cytokine release from macrophages by increasing chloride influx via a glycine-gated chloride channel.

Animals↗
PubMed1991

Glycine turnover and oxidation and hepatic serine synthesis from glycine in fetal lambs.

[1-13C]- and [1-14C]glycine were infused into chronically catheterized fetal lambs via a brachial vein. At tracer glycine steady state, samples were collected from the fetal abdominal aorta, umbilical vein, and fetal hepatic vein and from the maternal femoral artery and uterine vein. The samples were analyzed for plasma glycine and serine, for glycine and serine 13C atom% excess (APE), and for whole blood 14CO2 and O2 concentrations. Fetal plasma glycine disposal rate (DR) was 12.4 +/- 0.8 mumol.min-1.kg fetus-1.CO2 production from decarboxylation of fetal plasma glycine was 1.63 +/- 0.16 mumol.min-1.kg fetus-1 and represented 12.3 +/- 0.7% of DR. Approximately 50% of infused tracer glycine was taken up by the fetal liver with the release of labeled serine and CO2 in the fetal circulation. There was no detectable efflux of tracer glycine from the placenta into the maternal circulation. The tracer production of serine and CO2 accounted for 23 and 17%, respectively, of the hepatic tracer glycine uptake. The labeled CO2 released by the liver was a large fraction (approximately 70%) of the labeled CO2 produced by the fetus. The serine-to-glycine APE ratio in fetal plasma was approximately 5%. These results indicate that the fetal liver is the major site of fetal plasma glycine decarboxylation and of serine synthesis from plasma glycine.

Animals↗
PubMed1981

Glycine and benzoate conjugation and glycine acyltransferase activity in the developing and adult rat: possible relationships to nonketotic hyperglycinemia.

We report investigations of benzoate and glycine metabolism and glycine acyltransferase activity in rats. These studies provide insights related to the therapy and pathophysiology of human nonketotic hyperglycinemia. Liver acyltransferase activity increased sharply postnatally from low levels at birth, but transferase activity was absent in the brain. The enzyme level was unchanged in either organ after administration of 2,3,7,8-tetrachlordibenzodioxin, phenobarbital, benzoate or a high glycine diet. Brain and liver glycine levels remained unaltered during acute or chronic benzoate-induced reductions in plasma glycine levels. Plasma and brain glycine contents were measured in rats at different ages following a single injection of 3 mg glycine/g body weight; after injection, glycine levels in the brain were comparable in severely symptomatic neonatal rats and older asymptomatic rats, suggesting a similar glycine influx but a selective susceptibility of the newborn brain to toxicity from acute hyperglycinemia. When a 3.4% glycine diet was ingested for up to 30 days ad libitum, levels of plasma glycine rose about 4- to 5-fold from those achieved on a diet containing one tenth as much glycine, but brain and liver glycine concentrations increased only 2-fold or less in the chronically hyperglycinemic animals.

Acyltransferases↗
PubMed1991

The glycine cleavage system. The coupled expression of the glycine decarboxylase gene and the H-protein gene in the chicken.

Regulation of the transcription of the glycine decarboxylase gene and the H-protein gene was examined in chicken. Northern analysis suggested and run-off transcription confirmed that the glycine decarboxylase gene transcription is exclusively tissue-specific and takes place at different efficiencies in liver, kidney, and brain which are the chicken tissues exhibiting the glycine cleavage activity. No evidence for the glycine decarboxylase gene transcription was obtained in heart, spleen, and skeletal muscle. Basal and tissue-specific transcription of the H-protein gene can be distinguished. The tissue-specific transcription coordinates with transcription of the glycine decarboxylase gene in active tissues, while low abundance H-protein and its mRNA, products of the basal transcription, exist in inactive tissues together with small amounts of T-protein. Apparently, T-protein is synthesized by a process similar to that for H-protein. Glycine decarboxylase mRNA levels show a linear relationship with H-protein mRNA levels and with specific activities of the glycine cleavage reaction in active tissues. Tissue-specific distribution of the glycine cleavage activity is primarily determined by the expression of the glycine decarboxylase gene. The coordinate and tissue-specific transcription of the genes for the constituent proteins plays a key role in determining the magnitude of the glycine cleavage activity in chicken tissues and, thereby, the tissue-specificity of glycine metabolism.

Amino Acid Oxidoreductases↗
PubMed1980

The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria.

Glycine decarboxylase, tentatively called P-protein and considered a constituent of the glycine cleavage system, was purified to apparent homogeneity from chicken liver mitochondria. P-protein is a homodimer having a Mr = approximately 200,000 and consisting of identical subunits with Mr = approximately 100,000. Each subunit appears to contain an equimolar pyridoxal 5'-phosphate which is bound to the protein, possibly through a protonated aldimine linkage. The isoelectric point of P-protein was 7.2. P-protein could bind glycine, showing a Kd of 33 mM for it, and could catalyze glycine decarboxylation even though the rate of decarboxylation catalyzed by P-protein alone was extremely low. The product of glycine decarboxylation was methylamine and the Km for glycine. Methylamine could bind to P-protein, giving a Kd value of 63 mM, and it inhibited the glycine decarboxylation. P-protein alone could also slightly catalyze the exchange of carboxyl carbon of glycine with CO2 and the exchange appeared to obey a ping-pong mechanism. Both glycine decarboxylation and the glycine-CO2 exchange catalyzed by P-protein were stimulated 100-fold or more by the addition of lipoic acid, which is a functional group of H-protein. We may define P-protein as glycine decarboxylase although P-protein alone exhibits only very low catalytic activities.

Amino Acid Oxidoreductases↗
PubMed1979

Inhibition of glycine decarboxylation and serine formation in tobacco by glycine hydroxamate and its effect on photorespiratory carbon flow.

Glycine hydroxamate is a competitive inhibitor of glycine decarboxylation and serine formation (referred to as glycine decarboxylase activity) in particulate preparations obtained from both callus and leaf tissue of tobacco. In preparations from tobacco callus tissues, the K(i) for glycine hydroxamate was 0.24 +/- 0.03 millimolar and the K(m) for glycine was 5.0 +/- 0.5 millimolar. The inhibitor was chemically stable during assays of glycine decarboxylase activity, but reacted strongly when incubated with glyoxylate. Glycine hydroxamate blocked the conversion of glycine to serine and CO(2)in vivo when callus tissue incorporated and metabolized [1-(14)C]glycine, [1-(14)C]glycolate, or [1-(14)C]glyoxylate. The hydroxamate had no effect on glyoxylate aminotransferase activities in vivo, and the nonenzymic reaction between glycine hydroxamate and glyoxylate did not affect the flow of carbon in the glycolate pathway in vivo. Glycine hydroxamate is the first known reversible inhibitor of the photorespiratory conversion of glycine to serine and CO(2).

Journal Article↗