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P H Yu

Publications and source records attributed to P H Yu.

At least 145 records · Page 8Linked to original sources
PubMed1987

Irreversible inhibition of monoamine oxidase by some components of cigarette smoke.

Inhibitory activity towards monoamine oxidase has been found in a solution of cigarette smoke. The inhibition was irreversible. When tissue slices of rat lung were incubated in the cigarette smoke solution or alternatively, exposed directly to cigarette smoke, monoamine oxidase activities were reduced drastically. Similarly, human saliva after cigarette smoking also exhibits considerable MAO inhibitory activity. When the amine substrates p-tyramine, serotonin and beta-phenylethylamine were incubated with the cigarette smoke solution, lipophilic adducts were formed non-enzymatically. The irreversible inhibition of MAO by cigarette smoke may well be related to the low platelet MAO associated with cigarette smokers as previously reported. The implication of such cigarette smoke-caused reduction of MAO activity in relation to Parkinsonism is discussed.

Animals↗
PubMed1987

A behavioural and neurochemical analysis of chronic and selective monoamine oxidase inhibition.

The effects of clorgyline were compared with the effects of (-)-deprenyl using measures of rewarding hypothalamic self-stimulation, regional monoamine metabolism and monoamine oxidase activity. Male Wistar rats trained to self-stimulate at half-maximal rates with unilateral bipolar lateral hypothalamic electrodes on a continuous reinforcement schedule were implanted subcutaneously with osmotic minipumps which delivered 1 mg X kg-1 drug per day or vehicle for 13 days. A response rate/stimulation frequency (reward summation) function was determined the day before minipump implantation and on days 5 and 13 of drug administration. Only clorgyline induced a shift to the left in the reward summation function at 5 and 13 days, indicating enhancement of reinforcement. Clonidine (50 micrograms X kg-1 IP) probe tests were run on days 2 and 10 to determine the sensitivity of alpha 2-noradrenaline receptors. Clorgyline induced an attenuation of the clonidine response on day 10 relative to day 2. The other groups exhibited no change in response to clonidine. Clorgyline also induced a progressive increase in self-stimulation rates; this effect was not observed with the other groups. The clorgyline effects were accompanied by an increase in regional brain levels of dopamine, noradrenaline and 5-hydroxytryptamine and a reduction of their acid metabolites. Clorgyline selectively inhibited type A monoamine oxidase, whereas (-)-deprenyl selectively inhibited type B monoamine oxidase.

Animals↗
PubMed1987

Some aspects on L-dopa decarboxylase and p-tyrosine decarboxylase in the central nervous and peripheral tissues of the American cockroach Periplaneta americana.

1. Aromatic amino acid decarboxylase activities toward L-DOPA (L-3,4-dihydroxyphenylalanine), 5-HTP (5-hydroxytryptophan) and p-tyrosine in different tissues of the sclerotized and newly ecdysed cockroach were analyzed. 2. The ratios of enzyme activity with regard to L-DOPA and p-tyrosine varied considerably in the tissues and between the two different growth stages. 3. A DOPA decarboxylase and a p-tyrosine decarboxylase were separated by gel filtration and ion exchange chromatography. 4. The optimal pH requirement for both enzymes was 7.5 with the exception of the one decarboxylating 5-HTP. 5. The molecular weights of the cockroach brain DOPA decarboxylase and tyrosine decarboxylase were estimated to be 120,000 and 100,000, respectively. 6. Unlike the mammalian aromatic amino acid decarboxylase, the cockroach DOPA decarboxylase cannot be activated by a small amount of benzene. 7. An increase of over 50-fold of DOPA decarboxylase activity and a 50% reduction of tyrosine decarboxylase activity in the epidermal tissue of the newly ecdysed animals was observed. 8. In the fully sclerotized cockroach, a reversible endogenous inhibitor(s) of DOPA decarboxylase in the integument was observed, suggesting that the DOPA decarboxylase is suppressed in the epidermal tissues when ecdysis does not occur.

Animals↗
PubMed1987

Deuterium isotope effect in gamma-aminobutyric acid transamination: determination of rate-limiting step.

The rate of transamination of gamma-aminobutryic acid (GABA) catalyzed by hog brain gamma-aminobutyrate aminotransferase was substantially reduced when the hydrogen at the gamma-carbon position was replaced by deuterium. The deuterium isotope effect of this reaction has been substantiated by fluorometric, radiometric, and mass spectrometric procedures and assessed kinetically. The ratios of Vmax of the nonlabeled substrate/Vmax of the deuterated substrate obtained under different conditions ranged from 6 to 7. This indicates that the cleavage of the hydrogen from the gamma-carbon is the rate-determining step in GABA transamination. Similar isotope effects have also been shown to occur in the peripheral system in vivo.

4-Aminobutyrate Transaminase↗
PubMed1986

New sensitive high-performance liquid chromatographic method for p-tyrosine aminotransferase assay.

A rapid, sensitive and specific procedure has been developed for the determination of p-tyrosine aminotransaminase activity. The assay is based on high-performance liquid chromatography (HPLC) separation and electrochemical detection of the pyruvate product, which has been derivatized with hydroxylamine to form a stable oxime. Using this method the product at the low pmol level can be measured. A comparison of the kinetic parameters of the rat liver tyrosine aminotransferase and rat brain non-specific aspartate aminotransferase towards p-tyrosine has been made.

Animals↗
PubMed1986

Stereospecific deuterium substitution at the alpha-carbon position of dopamine and its effect on oxidative deamination catalyzed by MAO-A and MAO-B from different tissues.

Stereospecific replacement of deuterium in the alpha-carbon side chain position of dopamine (DA) was achieved by decarboxylation of L-3,4-dihydroxyphenylalanine (L-dopa) using hog kidney aromatic aminoacid decarboxylase. The S[alpha-2H1]DA enantiomer was obtained by decarboxylation of L-[alpha-2H1]dopa in H2O, while the R[alpha-2H1]DA enantiomer was obtained by decarboxylation of unsubstituted L-dopa in 2H2O. An inverse solvent isotope effect of L-dopa decarboxylation was observed in 2H2O. The deaminated aldehyde products of the four DA analogues, i.e. undeuterated DA, [alpha, alpha-2H2] DA, R[alpha-2H1]DA and S[alpha-2H1]DA, have been analyzed by the gas chromatography-mass spectrometry (GC-MS) method. It is evident that monoamine oxidase (MAO) catalyzes the stereochemical removal of only R-deuterium and that S-deuterium was maintained at the alpha-carbon atom of 3,4-dihydroxyphenylacetaldehyde. The steady-state kinetics of the oxidative deamination of undeuterated, [alpha, alpha-2H2], R[alpha-2H1], and S[alpha-2H1] dopamine were assessed by determination of the aldehyde products directly by high performance liquid chromatography (HPLC) using electrochemical detection (ECD). MAO-A from rat liver mitochondria (deprenyl-treated) and from human placenta, as well as MAO-B from rat liver (clorgyline-treated) and from human platelet were used in this study. The apparent isotope effects, i.e. (V/K)H/(V/K)D ratios of [alpha, alpha-2H2]DA and R[alpha-2H1]DA, were quite similar (2.34 and 3.13) with respect to both MAO-A and MAO-B. S[alpha-2H1]DA exhibited a slight secondary isotope effect. Formula: see text.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

High-performance liquid chromatography of aldehydes and acids formed in monoamine oxidase-catalyzed reactions.

A rapid, sensitive, and specific method for the determination of monoamine oxidase (MAO) activities toward different substrates is described. The assay is based on high-performance liquid chromatographic (HPLC) separation and electrochemical detection of the aldehyde or acid products. The aldehyde metabolic intermediates were observed to be quite stable in 0.1 N perchloric acid containing antioxidant and EDTA, and therefore can be used to measure the MAO activity of washed mitochondrial membrane and partially purified or purified MAO. Incomplete conversion of aldehyde to acid was observed when the amine substrates were incubated with the crude enzyme preparations. These aldehydes can be converted to corresponding acids by addition of yeast aldehyde dehydrogenase and beta-NAD and the acid can also be measured by HPLC-electrochemical detection. A deuterium isotope effect in the oxidation of p-[alpha,alpha-2H2]tyramine and [alpha,alpha-2H2]serotonin has been demonstrated by this method.

Acids↗
PubMed1986

Inhibition of monoamine oxidase activity by phenylpropanolamine, an anorectic agent.

Phenylpropanolamine (PPA) can cause hypertensive crisis in the event of abusive overdosage. It would be interesting to know if this is related to inhibition of monoamine oxidase (MAO) activity. PPA was found to inhibit both human brain and rat liver mitochondrial MAO activities in vitro, i.e. Ki's were 150 microM and 800 microM with respect to serotonin (Type A substrate) and beta-phenylethylamine (Type B substrate). The inhibition is competitive and reversible. PPA can also inhibit MAO-A activity in vivo at relatively high dose (50 mg/kg, i.p.), which was determined from an observation that PPA can protect MAO from the irreversible MAO inhibitor clorgyline. p-Tyramine levels were found to be increased in the urine after i.p. administration of PPA. Chronic administration of PPA does not induce any accumulative inhibitory effect on rat brain and liver MAO activities.

Animals↗
PubMed1985

Deuterium isotope effect in the transamination of p-tyrosine by rat liver tyrosine transaminase.

The rate of transamination of p-tyrosine catalyzed by rat liver soluble tyrosine aminotransferase (E.C. 2.6.1.5.) was significantly reduced when the hydrogen at the alpha-carbon position is replaced by deuterium or when the reactions were conducted in 2H2O. The cleavage of carbon-hydrogen bond at alpha-carbon position is at least partly involved in the rate-limiting step of tyrosine transamination. In 2H2O solvent the reduction of the overall rates of transamination of both p-tyrosine and alpha-2H1-p-tyrosine occurred uncompetitively which suggests that the deuterium solvent effect is involved in the tautomerization of the external Schiff's base.

Animals↗
PubMed1985

Effects of benzene and other organic solvents on the decarboxylation of some brain aromatic-L-amino acids.

The intraperitoneal administration of benzene produced marked increases in mouse striatal concentrations of beta-phenylethylamine, p-tyramine and, to a lesser extent, m-tyramine. Similar increases were observed in rat striatal p- and m-tyramine. The subcutaneous administration of benzene dissolved in sesame oil increased mouse striatal p-tyramine but did not change m-tyramine. Benzene administration to mice pretreated with p-tyrosine produced marked increases in mouse striatal p-tyramine as well as in m-tyramine. The statistical analysis of the results indicated that the treatment produced an interaction that led to an increase in the concentration of both the p- and m-isomers of tyramine. The administration of benzene to m-tyrosine-pretreated mice increased striatal m-tyramine but p-tyramine was not increased. The treatment produced no potentiation in the formation of p- or m-tyramine. Of the other organic solvents given, pyridine produced the most marked effects. Its administration increased the concentration of both p- and m-tyramine in the mouse striatum. Treatment with toluene, chloroform, carbon tetrachloride or isoamylalcohol produced moderate increases in mouse striatal p-tyramine while toluene, dichloromethane or isobutylalcohol also increased m-tyramine. These increases in brain beta-phenylethylamine, p-tyramine and m-tyramine may play a contributory role in the human toxicity of benzene and some of these organic solvents; these toxic effects could be exacerbated after ingestion of foodstuffs containing the aminoacids phenylalanine or p-tyrosine or for those under treatment with a monoamine oxidase inhibitor.

Animals↗
PubMed1985

Occurrence of phenolsulfotransferase in primary glial culture cells of rat.

Phenolsulfotransferase (PST) activity towards phenol and monoamines was determined in rat brain and in primary cultures of rat astrocytes. The pH requirement, Km values and the proportion of PST activity with respect to phenol and dopamine as substrates were similar between PST from the glial cells and the rat cortex. The enzyme activity increased with age in the brain of older animals, and also with increasing incubation time in the primary culture of astroglia. The specific PST activity of the astroglia appeared to be higher than that of the brain enzyme. In glial cultures treated with 0.25 mM dibutyryl cyclic AMP in the same culture conditions, PST activity is suppressed to about 25% of its untreated counterpart, even though dibutyryl cyclic AMP at concentrations of ImM only slightly inhibited PST activity in vitro.

Age Factors↗
PubMed1985

Sulfate conjugation of monoamines in human brain: purification and some properties of an arylamine sulfotransferase from cerebral cortex.

An arylamine sulfotransferase (PST-M) from human brain cortex that is involved in the formation of O-sulfate esters of monoamines has been purified 272-fold by ammonium sulfate fractionation, gel filtration, DEAE-cellulose ion-exchange chromatography, chromatofocussing, and hydroxyapatite chromatography. A molecular weight of 62,000, pK of pH 5.8, and an optimum pH for the reaction at 7.8-8.0 with respect to tyramines have been determined. This enzyme possesses an extremely high affinity for dopamine and m-tyramine based on the low Km values and is moderately active toward noradrenaline and p-tyramine. Serotonin is a poor substrate. In contrast, another sulfotransferase, PST-P, which has been separated from PST-M and partially purified, exhibited a very high affinity for phenol and nitrophenols but was inactive toward the amine sulfate acceptors. In the human brain the specific activity toward dopamine as well as the ratio of activity toward dopamine/phenol was considerably higher than those for rat, hog, and bovine brains.

Aged↗
PubMed1984

Monoamine oxidase in young and adult rat brain capillaries.

Capillaries were isolated from young and adult rat brain and the mitochondrial type A and B monoamine oxidase activities in these endothelial cells were determined. Type A activity was observed to be predominant in both young and adult rats and was increased with maturation while type B activity remained unchanged. The predominance of type A MAO in the rat brain capillaries is consistent with that of the rat aorta and heart tissue.

Age Factors↗
PubMed1984

Photoactivated linkage of catechol O-methyltransferase and S-adenosyl-L-methionine.

The formation of a stably linked complex of tritiated S-adenosyl-L-methionine (AdoMet) and catechol O-methyltransferase (COMT) has been achieved by irradiating the enzyme and ligand in Tris-HCl buffer (pH 7.5) with ultraviolet light at 254 nm. The reaction is specific as shown by a number of criteria. COMT inhibitors such as S-adenosylhomocysteine can block this photoactivated linkage. The [3H]AdoMet-COMT adduct has been shown to be a homogeneous protein by Sephadex gel filtration, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and isoelectric focussing. After extensive proteolysis of the [3H]AdoMet-COMT adduct with pronase P, one major labelled product was released. This fragment could be separated by paper chromatography and was shown to be chromatographically identical to that released from the [3H]AdoMet-phenylethanolamine N-methyltransferase adduct.

Animals↗
PubMed1983

Potentiation of the biochemical effects of beta-phenylethylhydrazine by deuterium substitution.

The concentrations of dopamine (DA), m-tyramine (mTA), p-tyramine (pTA) and serotonin (5-HT) in the striata of rats 18 hr after the administration of three different doses (5, 50, or 100 mg/kg) of beta-phenylethylhydrazine (phenelzine, PEH) were measured. These concentrations were compared to those following the administration of the same doses of 1,1,2,2-tetradeutero-PEH (d4PEH). In general, PEH and d4PEH caused dose-dependent increases in the levels of mTA, pTA and 5-HT. The lowest dose of d4PEH caused greater increases than PEH in the levels of all four monoamines. The concentration of 5-HT was increased more by d4PEH than PEH at all three doses. The inhibition of mitochondrial MAO obtained from rat striatum by PEH or d4PEH in vitro revealed no differences. However, the inhibition of striatal MAO obtained from rats injected with d4PEH was found to be greater than that from rats injected with PEH. It was concluded that deuteration of PEH potentiates its ability to inhibit MAO following its administration to the rat by slowing its degradation in vivo.

Animals↗