Accumulation Of Formaldehyde Research Articles

The scheme of methanol oxidation at a platinum electrode in an acid solution

The scheme of methanol oxidation at a platinum electrode in a sulphuric acid solution was investigated by potential step and product-analysis methods. The potential step method revealed that dissolved formaldehyde accumulated in the vicinity of the electrode surface during methanol oxidation at potentials of about 0.6–0.8 V. Its accumulation occurred also at low methanol concentrations at which the bulk concentration of the formaldehyde was small. The rates of formaldehyde oxidation obtained and its accumulation showed that carbon dioxide was formed predominantly via dissolved formaldehyde at about 0.75–0.80 V, while at lower potentials its formation did not occur via dissolved formaldehyde. High methanol concentrations favoured the accumulation of formaldehyde in the bulk solutions.

Glutathione conjugation and cytochrome P-450 metabolism of methyl chloride in vitro

Possible carcinogenic properties of methyl chloride (CH 3Cl) have been under discussion since an increase of renal tumours was observed in male B6C3F 1 mice after a 2-yr inhalation exposure to the substance. This was, however, only observed following exposure of male mice to the highest concentration level and not after exposure of females or F344 rats of both sexes. Accumulation of formaldehyde in the kidneys was thought to be responsible for tumour production. In the experiments presented here, cytosolic enzymes from the liver and kidneys of different mouse strains and F344 rats were incubated in head-space vials with methyl chloride or methyl bromide. Following equilibration, the decrease in the concentration of the gases was monitored by gas chromatography as a parameter for metabolic elimination. The metabolic turnover of the methyl halides was found to be significantly higher in female animals than in the males. In parallel experiments, the glutathione content of the liver and kidneys of mice exposed by inhalation to 1000 ppm methyl chloride was determined. In both organs, the glutathione content diminished rapidly after exposure to the methyl halide. The glutathione depletion was slightly greater in females than in males. Finally, the content of cytochromes P-450, P-420 and b5 was determined in liver and kidneys of different mouse strains by difference spectroscopy. Female mice were found to have a lower content of P-450 and b5 than males in the kidneys; there was no such sex difference in liver tissue. The results show that a sex difference in metabolism is unlikely to be responsible for the unique kidney tumour production in male B6C3F 1 mice. Other possible explanations are discussed.

Isolation and characterization of mutants of the facultative methylotroph Arthrobacter P1 blocked in one-carbon metabolism

Among methylamine and/or ethylamine minus mutants of Arthrobacter P1 four different classes were identified, which were blocked either in the methylamine transport system, amine oxidase, hexulose phosphate synthase or acetaldehyde dehydrogenase. The results indicated that a common primary amine oxidase is involved in the metabolism of methylamine and ethylamine. Growth on ethylamine, however, was not dependent on the presence of the methylamine transport system. In mutants lacking amine oxidase, methylamine was unable to induce the synthesis of hexulose phosphate synthase, thus confirming the view that the actual inducer for the latter enzyme is not methylamine, but its oxidation product formaldehyde. Contrary to expectation, when the formaldehyde fixing enzyme hexulose phosphate synthase was deleted (mutant Art 11), accumulation of formaldehyde during growth on choline or on glucose plus methylamine as a nitrogen source did not occur. Evidence was obtained to indicate that under these conditions formaldehyde may be oxidized to carbon dioxide via formate, a sequence in which peroxidative reactions mediated by catalase are involved. In addition, a specific NAD-dependent formaldehyde dehydrogenase was detected in choline-grown cells of wild type Arthrobacter P1 and strain Art 11. This enzyme, however, does not play a role in methylamine or formaldehyde metabolism, apparently because these compounds do not induce its synthesis.

Inhibition of CO 2 production from aminopyrine or methanol by cyanamide or crotonaldehyde and the role of mitochondrial aldehyde dehydrogenase in formaldehyde oxidation

Previous results have shown that cyanamide or crotonaldehyde are effective inhibitors of the oxidation of formaldehyde by the low- K m mitochondrial aldehyde dehydrogenase, but do not affect the activity of the glutathione-dependent formaldehyde dehydrogenase. These compounds were used to evaluate the enzyme pathways responsible for the oxidation of formaldehyde generated during the metabolism of aminopyrine or methanol by isolated hepatocytes. Both cyanamide and crotonaldehyde inhibited the production of 14CO 2 from 14C-labeled aminopyrine by 30–40%. These agents caused an accumulation of formaldehyde which was identical to the loss in CO 2 production, indicating that the inhbition of CO 2 production reflected an inhibition of formaldehyde oxidation. The oxidation of methanol was stimulated by the addition of glyoxylic acid, which increases the rate of H 2O 2 generation. Crotonaldehyde inhibited CO 2 production from methanol, but caused a corresponding increase in formaldehyde accumulation. The partial sensitivity of CO 2 production to inhibition by cyanamide or crotonaldehyde suggests that both the mitochondrial aldehyde dehydrogenase and formaldehyde dehydrogenase contribute towards the metabolism of formaldehyde which is generated from mixed-function oxidase activity or from methanol, just as both enzyme systems contribute towards the metabolism of exogenously added formaldehyde.

In vivo 13C NMR Investigations of Methanol Oxidation by the Obligate Methanotroph Methylosinus trichosporium OB3b

In vivo 13C NMR has been used to observe metabolism of exogenously supplied methanol by suspensions of Methylosinus trichosporium OB3b grown under a variety of conditions. Formaldehyde, formate and bicarbonate ions were the only metabolites of methanol to be detected. Accumulation of formaldehyde was observed only with suspensions grown under conditions which yield particulate, membrane-bound, methane mono-oxygenase (MMO). Ethyne abolished MMO activity, partially inhibited methanol oxidation in whole organisms, and prevented growth of the organism on methanol (1%, v/v) in batch culture. Oxidation of ethanol, a substrate of methanol dehydrogenase, was not affected by ethyne. Ethyne caused accumulation of formaldehyde in all suspensions of the organism incubated with methanol, although oxidation of exogenously added formaldehyde was not affected. These observations are consistent with the proposal that in M. trichosporium OB3b both MMO and methanol dehydrogenase oxidize exogenously supplied methanol and suggest that the further oxidation of formaldehyde is stimulated by the consumption of reducing equivalents by MMO.

Trimethylamine N-oxide demethylase: Its occurrence, properties, and rôle in technological changes in frozen fish

Trimethylamine N-oxide (TMAO) is a natural, characteristic component of muscle tissues and visceral organs of sea fish and invertebrates. In about thirty species of fish and eight species of invertebrates TMAO is broken down post mortem to dimethylamine (DMA) and formaldehyde (FA). The enzyme catalysing this reaction is present in the muscles, skin and visceral organs. The available published information indicates that the enzymes differ in molecular weight and requirements of cofactors, depending upon the source of isolation. However, glutathione, ferrous chloride, ascorbic acid, methylene blue and flavonucleotide activate the demethylase from various sources. The optimum pH for TMAO demethylation is from 5·0 to 7·5. Freezing and frozen storage do not destroy the activity of TMAO demethylase. The rate of enzymatic cleavage of TMAO to FA and DMA depends on the substrate and FA. In numerous observations it was found that during frozen storage of fish belonging to the Gadoid family a progressive accumulation of DMA and FA takes place and is accompanied by a decrease in protein extractability and deterioration of the textural properties of the flesh.

ASSESSMENT OF ENVIRONMENTAL POLLUTION BY FORMALDEHYDE IN RENAL DIALYSIS UNITS

An assessment of the environmental pollution from the use of formaldehyde solutions in dialysis units indicated that spillages from manual washout systems and fluids exposed during semi-automated washouts were the greatest source of contamination. Inadequate air exchange also allowed accumulation of atmospheric formaldehyde to rise above the threshold limit values (TLV) ceiling of 2 ppm and to reach 25 ppm. Improvements in the air extraction systems, the introduction of closed drainage and staff guidance resulted in safe working conditions. Additionally a planned monitoring programme and an ongoing staff training scheme are recommended wherever formaldehyde is used in appreciable quantities.

Methane metabolism of the obligate methane-utilizing bacterium, Methylomonas flagellata, in methane-limited and oxygen-limited chemostat culture.

The effect of a limited supply of methane and oxygen on growth of Methylomonas flagellata was analyzed in chemostat culture. A significant decrease in YCH4 was observed under oxygen-limitation. Accumulation of formaldehyde is supposed to cause a decrease of YCH4. A low level of formaldehyde oxidizing activity in cells grown under oxygen-limited steady-states suggests that formaldehyde dehydrogenase is repressed under oxygen deficiency. In spite of the suppression of respiration, methane oxidation progressed independently under oxygen-limitation. These facts support the idea that methanol oxidation couples with methane oxidation (a mono-oxygenase system) in this microorganism.

Methanol poisoning VI: role of folic acid in the production of methanol poisoning in the rat.

Methanol poisoning is well known to occur in humans but does not develop in common laboratory animals such as the rat. Rodents display neither metabolic acidosis nor ocular toxicity after methanol treatment, findings that commonly result in humans and that have recently been described in the monkey. Since methanol administration in the monkey leads to marked accumulation of formic acid and metabolic acidosis, experiments were devised to reduce formate metabolism in the rat and thereby study whether methanol administration would lead to the accumulation of formic acid and acidosis in that species. Several methods were employed to induce a state of folate deficiency in the rat, a prerequisite to producing a decrease in formate oxidation to CO2 in that species. Rats placed on a folate‐deficient diet for 10–12 wk showed a marked decrease in formate oxidation and a marked sensitivity to methanol poisoning, as evidenced by high blood formate levels and marked decreases in blood pH. Treatment of rats with methotrexate was relatively ineffective in inducing decreases in formate oxidation, but in rats fed a folate‐deficient diet for 9 days and injected once daily for 9 days with 1 mg/kg methotrexate, a significant elevation of blood formate and decrease in blood pH was observed. In rats that were acidotic following methanol administration no accumulation of formaldehyde was observed. These results indicate that it is possible to sensitize the rat to methanol poisoning by reducing its capacity to oxidize formate. They also show that once the rat is susceptible to methanol poisoning, metabolic acidosis and formate accumulation occur without the accumulation of formaldehyde.

Acid catalysed degradation of polyoxymethylene in aqueous solutions of hexafluoroacetone

A study was made of the kinetics of degradation of polyoxymethylene oligomers and polymers of different molecular weight, with different endgroups, in hydrochloric acid-water-hexafluoroacetone solutions. It is shown that the effective rate of degradation depends on the concentration of hydrochloric acid and water in hexafluoroacetone. An equation describing the accumulation of formaldehyde during the degradation of polyoxymethylene is proposed, and the depolymerization rate constant has been calculated.

The oxidation of neopentane

The gas phase oxidation of neopentane has been studied in a static system at 280 °C. It is shown that the main course of the reaction is best understood as a degenerately branched chain reaction propagated by the hydroxyl radical. Two simultaneous radical chain mechanisms arise from the decomposition of the transient unstable species neopentylperoxy to give on the one hand either isobutyraldehyde and carbon monoxide, or isobutene and acetone, and on the other hand isobutene and formaldehyde possibly via oxetane. Isobutene and isobutyraldehyde do not accumulate as end products of the reaction, but are further oxidized to acetone and carbon monoxide. Pivalaldehyde and isobutene are the first detectable intermediate products, and the former is primarily responsible for the degenerate branching mechanism. It is concluded that the accumulation of formaldehyde in the system can account for an apparent change from homogeneous to heterogeneous chain termination as the reaction proceeds.

Kinetics of the gas-phase oxidation of methanol catalysed by hydrogen bromide

The homogeneous, gas-phase oxidation of methanol, catalysed by small amounts of hydrogen bromide, has been studied in a boric acid coated vessel at 310�. Under these conditions no reaction takes place in the absence of hydrogen bromide. The kinetics of the reaction and the rate of accumulation of formaldehyde in the products are compared with previously published data on the nitric oxide catalysed reaction at 310� and the uncatalysed reaction at 390�, i.e. at comparable rates of oxidation. The kinetics of the reaction were studied by means of pressure-time curves, and these were found to be of a similar shape to those of the uncatalysed reaction at 390�, and the nitric oxide catalysed reaction at 310�. The maximum rate was increased by the addition of "inert" gas. This rate varied as the methanol and hydrogen bromide pressures raised to the powers 0.7 and 1.3 respectively. On the other hand, increase in the oxygen pressure inhibited the maximum rate. The overall activation energy was 27 kcal mole-1. These kinetic data are similar to those of the nitric oxide catalysed reaction but differ markedly from those of the uncatalysed process at 390�. Under similar conditions, 15 mmHg hydrogen bromide were required to give a rate approximately equal to that obtained when using 2 mmHg nitric oxide. The maximum pressure of formaldehyde in the products was only about one-tenth of that obtained under similar conditions in the other two oxidations.

Studies on the effect of other alcohols on the metabolism of methanol in rat liver homogenates.

Abstract.The effect of various lower aliphatic aloohols on the accumulation of formaldehyde in rat liver homogenates incubated with methanol has been studied. The addition of ethanol inhibited very clearly the accumulation of formaldehyde, n‐propanol, isopropanol or n‐butanol had no effect on the accumulation of formaldehyde.

Effect of disulfiram (tetraethylthiuram disulphide) on the metabolism of methanol in rat liver homogenates.

Abstract.The effect of disulfiram on the accumulation of formaldehyde in liver homogenates incubated with methanol has been studied in rats after feeding them high doses of disulfiram (1.0–4.5 g per kg daily for 9 days). The catalase and xanthine oxidase activities of the livers have also been determined. The formation of formaldehyde has been determined photometrically. The accumulation of formaldehyde in the liver homogenates from disulfiram‐treated rats was not increased, but slightly inhibited by almost lethal doses. It was not stimulated by ATP as in normal animals. The liver catalase activity was clearly lowered in the disulfiram‐treated rats. The liver xanthine oxidase activity was also diminished in these rats but not constantly.