Plasma Amine Oxidase Activity Research Articles

A Case of Isoniazid-Induced Delirium

A Case of Isoniazid-Induced Delirium

Determination of Semicarbazide-Sensitive Amine Oxidase Activity in Blood Plasma by a Light Scattering Technique

A novel method for the determination of semicarbazide-sensitive amine oxidase (SSAO) activity in blood plasma has been developed. The method was based on the change of light scattering (LS) intensity resulting from the derivative product of the interaction of 2,4-dinitrophenylhydrazine (DNPH) with benzaldehyde produced by catalyzing of SSAO to benzylamine. In Britton-Robinson (B-R) buffer solution, the intensity of system's LS at 514.6 nm was significantly enhanced and was directly proportional to the concentration of benzaldehyde. In this method, SSAO enzyme activity is defined as the concentration of benzaldehyde (nmol) formed per mL plasma per hour. The range of determination of SSAO enzyme activity was 6.40 × 10−3 −0.340 nmol mL−1 h−1 with a detection limit of 1.92 × 10−3 nmol mL−1 h−1. The relative standard deviation was 2.8–4.1% and the average recovery was 67.9% (n = 6).

The origin of mammalian plasma amine oxidases

Mammalian blood plasma contains considerable activity of soluble copper-containing amine oxidase (AOC) referred to as plasma or serum amine oxidase (SAO). The identity and origin of SAO was investigated based on the recent characterization of four porcine AOC genes with AOC1 encoding diamine oxidase (DAO), AOC2 retina-specific amine oxidase (RAO), AOC3 vascular adhesion protein-1 (VAP-1), and AOC4 a VAP-1 homologue that is expressed mainly in the liver and has a signal peptide sequence instead of a transmembrane domain at its N-terminus. Purification and characterization of the major amine oxidase activity from porcine serum showed that it is the product of the AOC4 gene. Intriguingly, all mammals possessing a functional AOC4 gene exhibit high plasma amine oxidase activity. Humans and rodents lack a functional AOC4 gene and have comparably low plasma amine oxidase activity that is probably derived from partial proteolytic release of the membrane-associated AOC3 gene product VAP-1.

Semicarbazide-sensitive amine oxidase in transgenic mice with diabetes

Semicarbazide-sensitive amine oxidase (SSAO) activity in plasma is increased in diabetes, and in particular, in diabetic patients with vascular complications. It has been speculated that SSAO is involved in the development of such complications due to the production of cytotoxic compounds. In this work, we have induced diabetes in a previously described mouse-model, overexpressing SSAO in smooth muscle cells. SSAO activity was estimated as well as expression of the endogenous mouse gene and human transgene using real-time PCR. Diabetes induced an increase in SSAO activity in serum, kidney, and adipose tissue of transgenic animals. An inverse correlation between SSAO activity and mouse SSAO mRNA levels was observed in transgenic animals with diabetes. These results further support the suggestion of a negative feedback control of the SSAO gene expression. The increased SSAO activity in diabetes is most likely dependent on post-transcriptional modifications or activation of existing inactive enzyme molecules.

Acrolein produced from polyamines as one of the uraemic toxins.

It is well known that the addition of spermine or spermidine to culture medium containing ruminant serum inhibits cellular proliferation. This effect is caused by the products of oxidation of polyamines that are generated by serum amine oxidase. Among the products, we found that acrolein is a major toxic compound produced from spermine and spermidine by amine oxidase. We then analysed the level of polyamines (putrescine, spermidine and spermine) and amine oxidase activity in plasma of patients with chronic renal failure. It was found that the levels of putrescine and the amine oxidase activity were increased, whereas spermidine and spermine were decreased in plasma of patients with chronic renal failure. The levels of free and protein-conjugated acrolein were also increased in plasma of patients with chronic renal failure. An increase in putrescine, amine oxidase and acrolein in plasma was observed in all cases such as diabetic nephropathy, chronic glomerulonephritis and nephrosclerosis. These results suggest that acrolein is produced during the early stage of nephritis through kidney damage and also during uraemia through accumulation of polyamines in blood due to the decrease in their excretion into urine.

Alterations in plasma amine oxidase activities in a compartment syndrome model.

Alterations in plasma amine oxidase activities in a compartment syndrome model.

Michaelis-Menten analysis of bovine plasma amine oxidase by capillary electrophoresis using electrophoretically mediated microanalysis in a partially filled capillary.

A method for determining bovine plasma amine oxidase (PAO; EC 1.4.3.6) activity with benzylamine (Bz) as substrate is described. Electrophoretically mediated microanalysis (EMMA) combined with micellar electrokinetic capillary chromatography (MEKC) was used to perform an on-capillary enzymatic reaction and to separate the generated benzaldehyde from the other reaction products. The capillary was only partially filled with the separation solution, since the enzyme was unstable in the presence of the applied surfactant. The initial reaction velocity of the enzyme-catalyzed reaction was estimated from the peak area of the enzyme product, benzaldehyde. An amplification step was introduced by means of an on-capillary incubation of 15 min, in order to accumulate enough reaction product to detect spectrophotometrically at 254 nm. This set-up resulted in a fully automated assay, which can be carried out in less then 35 min. Using the Lineweaver-Burk equation, an average Michaelis constant (K(M)) for PAO was calculated to be 0.74 mM +/- 0.05 mM, which is consistent with previously reported values.

Determination of semicarbazide-sensitive amine oxidase activity in human plasma by high-performance liquid chromatography with fluorimetric detection.

We report here a simple and sensitive method for the measurement of semicarbazide-sensitive amine oxidase (SSAO) activity in human plasma. Benzaldehyde, generated during a 1-h incubation of plasma with benzylamine, is derivatized with the specific aldehyde reagent dimedone after prior deproteinization. Quantitation of the derivatization product is done by automated injection onto an isocratic high-performance liquid chromatographic system with fluorimetric detection. The assay shows good linearity and reproducibility (intra-assay C.V. 7%). Detection limit is 25 mU/l (= pmol/ml/min). In 51 healthy controls (age 49 +/- 13 yr, 20 males) the measured SSAO activity was 352 +/- 102 mU/l (mean +/- S.D.). A large number of samples (70-80) can easily be processed in one day by one technician.

Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase

Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal. To investigate other deaminating systems besides MAO-A and MAO-B that might produce these metabolites of dopamine and 5-HT, we examined plasma amine oxidase (AO) activity in these two patients and two additional patients with the same X-chromosomal deletion. Normal plasma AO activity was found in all four Norrie disease-deletion patients, in four patients with classic Norrie disease without a chromosomal deletion, and in family members of patients from both groups. Marked plasma amine metabolite abnormalities and essentially absent platelet MAO-B activity were found in all four Norrie disease-deletion patients, but in none of the other subjects in the two comparison groups. These results indicate that plasma AO is encoded by gene(s) independent of those for MAO-A and MAO-B, and raise the possibility that plasma AO, and perhaps the closely related tissue AO, benzylamine oxidase, as well as other atypical AOs or MAOs encoded independently from MAO-A and MAO-B may contribute to the oxidative deamination of dopamine and 5-HT in humans.

Plasma amine oxidase and clinical features of schizophrenia.

Among 76 chronic schizophrenic patients, plasma amine oxidase activity was unrelated to paranoid/nonparanoid subtype, narrow/broad diagnostic criteria, prognosis, or age at onset. These clinical indices do not identify biological subtypes of schizophrenia with deviant plasma amine oxidase activity.

Genetic analysis of plasma amine oxidase activity in schizophrenia

Plasma amine oxidase (PAO) activity has been implicated in the biology of schizophrenia. PAO activity is, in part, under genetic control, but its mode of inheritance has not been determined. To assess the genetic pattern of PAO activity and its relation to the transmission of schizophrenia, we studied 73 chronic schizophrenia probands and 217 first-degree relatives (siblings and parents). Single-major-locus hypotheses were tested by pedigree analysis methods for quantitative traits. The distribution of PAO activity indicated significant admixture. When the transmission probability model was used, the familiar pattern of PAO activity was consistent with mendelian transmission; the environmental hypothesis was rejected. PAO activity was lower in schizophrenic patients than in unaffected relatives, but the mean reduction in enzyme activity was small (10.7%) and the two groups of subjects overlapped greatly in their PAO values. The difference between ill and well relatives was not statistically significant. However, schizophrenia spectrum disorders segregated with low PAO activity in families of low-activity probands, and a greater proportion of ill than well subjects clustered in the low PAO activity mode. The results are interpreted as follows: (1) The transmission of PAO activity may be determined in part by a single major autosomal gene. (2) Low PAO activity does not qualify as a major risk factor in the schizophrenic population at large; however, a relationship may exist between low PAO activity and the transmission of schizophrenia in families of patients with extremely low enzyme activity.

Enzyme activity in Tourette's syndrome.

Activity levels of platelet monoamine oxidase (MAO), plasma amine oxidase (PAO), erythrocyte catechol-o-methyltransferase, and dopamine-beta-hydroxylase were measured in 24 drug-free patients with Tourette's syndrome (TS) and in 24 normal control subjects matched for age and sex. Only MAO and PAO activity levels were significantly higher in patients than in controls. Activity of the four enzymes was uncorrelated with age, sex, age of onset of illness, severity of illness, family history of tics and Ts, and ethnic-religious background. The hypothesis that probands with heavily loaded pedigrees or with Ashkenazi ethnic-religious background would be more biochemically deviant was not supported.

The effect of feed restriction on certain haematological indices, enzymes and metabolites in Nubian goats

1. 1. Some effects of restricting feed intake for 96 or 168 hr were determined in male Nubian goats. 2. 2. Goats restricted for 96 hr lost 11.6% of their body weight, and goats restricted for 168 hr lost 19.8%. 3. 3. Feed restriction for up to 168 hr did not produce significant effects on the heart rate, respiratory rate or rectal temperature. 4. 4. Haemoglobin concentration, packed cell volume and erythrocyte number were all decreased by feed restriction. There was also a tendency towards eosinopenia and lymphopenia. 5. 5. Feed restriction for 96 or 168 hr raised the plasma activity of aspartate transaminase, and did not affect significantly cholinesterase activity. Plasma amine oxidase activity was significantly reduced in goats restricted for 168 hr. 6. 6. Feed restriction produced significant increases in the blood or plasma concentrations of lactate. pyruvate, non-esterified fatty acids, cholesterol, ketone bodies and bilirubin. 7. 7. Significant decreases were found in the concentrations of total protein and calcium. 8. 8. No significant changes were observed in the plasma concentrations of glucose, sodium or potassium.

Plasma amine oxidase and genetic vulnerability to schizophrenia.

Plasma amine oxidase (PAO) activity was studied in 52 chronic schizophrenics, 130 first-degree relatives, and 36 normal control subjects. Enzyme activity was shown to be a heritable and stable characteristic. Age and sex effects were not present. Patients had lower PAO activity than did control subjects, although the difference fell short of statistical significance. Within families, reduced PAO activity was associated with schizophrenia spectrum disorders.

Platelet monoamine oxidase and plasma amine oxidase: effect of anticoagulant and centrifugation technique on platelet yield and enzyme activity.

Platelet recovery and activity of platelet monoamine oxidase (MAO) and plasma amine oxidase (PAO) were determined using different centrifugation procedures (125 g for 15 min vs. 600 g for 2.5 min) and anticoagulants. With either centrifugation procedure, the use of ethylenediaminetetraacetate (EDTA) as anticoagulant resulted in higher platelet yields and MAO activity compared to acid-citrate-dextrose (ACD). However, PAO activity was lower with EDTA as anticoagulant than with ACD. There was a trend toward higher platelet yields and higher activity levels of MAO and PAO with the 125 g centrifugation method than with the 600 g technique regardless of the anticoagulant used. The implications for MAO studies in psychiatric research were discussed.

Neuroleptic drug effect on platelet monoamine oxidase and plasma amine oxidase in schizophrenia

Activity levels of platelet monoamine oxidase (MAO) and plasma amine oxidase (PAO) were determined in eight chronic schizophrenic patients who had been treated with neuroleptic drugs for 3 months. The mean reduction in platelet MAO activity was 18.6%;. The extent of decrease was statistically significant. The reduction in enzyme activity was unrelated to serum iron levels. PAO activity was unaltered. The implications for schizophrenia research are discussed.

Kinetic determination of plasma amine oxidase photometric test with aldehyde dehydrogenase

Of three different methods for the determination of plasma amine oxidase activity we found the method with coupled aldehyde dehydrogenase to show the least interferences and to give reliable results with unfractionated samples, e. g. human plasma. From our inhibitor studies we concluded that no flavine containing amine oxidase (MAO) could be detected in human plasma and that all detectable amine oxidase activity in plasma was attributable to Cu-amine oxidases.

Blood tryptophan metabolism in chronic schizophrenics.

Concomitant measures of blood indole metabolism were conducted in 33 chronic schizophrenics who showed significantly elevated mean platelet serotonin (5-HT) values and lower platelet monoamine oxidase (MAO) and plasma amine oxidase activities than normals. When subdivided according to Research Diagnostic Criteria diagnosis, the 20 chronic undifferentiated (CU) schizophrenics showed these same deviations from normal; the 13 chronic paranoid (CP) schizophrenics also had significantly higher mean 5-HT values but significantly lower plasma concentrations of total and bound tryptophan. In CP schizophrenics, platelet MAO activity, but not plasma amine oxidase activity, was significantly lower than in CU schizophrenics and controls. Hyperserotonemia occurred in 11 of the chronic patients (33%); nine were CU schizophrenics. In the latter, total tryptophan concentration was significantly lowered. Hyperserotonemia was not associated with reduced liver tryptophan pyrrolase activity or platelet MAO or plasma amine oxidase activities; rather, it may be a consequence of enhanced tissue tryptophan uptake and utilization.

Cord blood amine oxidase activities relate to arousal and motor functioning in human newborns

To examine relationships between amine oxidase activities and behavior prior to significant postnatal experience, umbilical cord blood samples were collected from 28 normal infants, and the Brazelton Neonatal Behavioral Assessment Scale was administered within 72 hours of birth. Infants with lower platelet monoamine oxidase (MAO) and/or lower plasma amine oxidase activity were more highly aroused, more motorically active and more difficult to console than those with higher MAO activity. These behavioral characteristics are remarkably similar to the more elaborate affective and social features which have previously been associated with MAO activity differences in adult humans and rhesus monkeys.

Elevation of human plasma and platelet amine oxidase activity in response to intravenous dopamine

Healthy male volunteers were infused for three hours with either a dopamine hydrochloride solution at a rate of 4 ug/kg/min or with normal saline. Plasma amine oxidase and platelet MAO activity towards benzylamine both increased in response to intravenous dopamine. There was no increase in enzyme activity when dopamine was added to the platelet and plasma enzymes in vitro. This heretofore unreported increase in the oxidative deaminating capacity of the human organism may represent an adaptive physiologic response to the high circulating levels of dopamine and provides further evidence for a possible functional significance of these enzymes in man.