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PubMedDate not supplied

Catalase mediated conversion of cyanamide to an inhibitor of aldehyde dehydrogenase.

A minor pathway for cyanamide metabolism catalyzed by catalase is responsible for the conversion of cyanamide to an inhibitor of aldehyde dehydrogenase. Catalase itself is also inhibited by cyanamide. Both the activation of cyanamide by catalase and the inhibition of catalase by cyanamide were blocked in vivo by ethanol pretreatment, suggesting that these two processes are closely linked. Like other catalase oxidation reactions, the catalase mediated activation of cyanamide was inhibited by 3-amino-1,2,4-triazole in vivo and sodium azide in vitro. The relative formation of the active cyanamide metabolite was assessed in vitro by following the loss of yeast aldehyde dehydrogenase activity with time. Inhibition of the yeast enzyme by activated cyanamide was dependent on NAD+ or NADP+, a requirement not fulfilled by NADH or NADPH. Although H2O2 inhibited yeast aldehyde dehydrogenase in vitro and cyanamide inhibited hepatic catalase in vivo, the possible in hepatic H2O2 concentration following cyanamide administration does not account for the effects of cyanamide on ethanol metabolism. While the cyanamide activating enzyme has been identified as catalase, the reaction products of this reaction and, in particular, the structure of the active metabolite involved in the inhibition of aldehyde dehydrogenase remain unknown.

Aldehyde Dehydrogenase↗

PubMed1983

Metabolic activation of cyanamide to an inhibitor of aldehyde dehydrogenase in vitro.

The inhibition of aldehyde dehydrogenase (AIDH) by cyanamide is dependent on the conversion of the latter to an active metabolite. This accounts for the in vivo activity of cyanamide in raising ethanol-derived blood acetaldehyde levels to the mM range in the rat (ED50 for cyanamide = 0.11 mmole/kg) and its lack of inhibitory activity in vitro with purified AIDH enzymes. Liver mitochondria were shown to catalyze this activation. The Low Km mitochondrial AIDH isozyme was strongly inhibited by cyanamide when measured in intact rat liver mitochondria (I50 = 2.0 microM). Cyanamide also inhibited yeast AIDH when incubated in the presence, but not in the absence, of rat liver mitochondria (I50 = 7.8 microM). Using yeast AIDH activity as a measure of cyanamide activation, the subcellular distribution of the cyanamide-activating system was assessed. Microsomes plus an NADPH generating system were equally active as mitochondria in activating cyanamide. In the absence of NADPH, microsomal activity was about half that of mitochondria. Little or no activity was found in the cytosolic fraction. A series of cyanamide analogs and derivatives were screened for their ability to inhibit the low Km AIDH isozyme measured in intact mitochondria. Only monoalkylcyanamides exemplified by n-butylcyanamide showed significant inhibition. Other cyanamide analogs and derivatives including N-acetylcyanamide, the major urinary metabolite of cyanamide, were inactive in this system.

Acetaldehyde↗

PubMed1985

Enzymatic requirement for cyanamide inactivation of rat liver aldehyde dehydrogenase.

The in vitro inactivation of aldehyde dehydrogenase (ALDH) by cyanamide in rat liver slices, in intact mitochondria, and at various stages of purity was characterized. Low-Km ALDH was more susceptible to cyanamide inactivation than was the high-Km form. In addition, the presence of NAD or NADH was necessary for cyanamide inhibition of the ALDH activity. Cyanamide at low concentrations required enzymatic conversion to a reactive derivative that could inhibit ALDH. The data in this study are consistent with the suggestion of DeMaster et al. [Biochem. biophys. Res. Commun., 122, 358 (1984)] that catalase is the cyanamide-converting enzyme. An inhibitor of catalase activity, malonate, decreased the rate of cyanamide inactivation of ALDH in intact mitochondria. Furthermore, affinity chromatography-purified ALDH, free of catalase activity, was not susceptible to cyanamide inactivation. This affinity-purified ALDH was only inactivated by high concentrations of cyanamide. Thus, an alternative pathway for ALDH inactivation may exist in which enzymatic modification of cyanamide is not necessary. It is more likely, however, that a contaminating enzyme in the ALDH preparation is capable of activating cyanamide.

Aldehyde Dehydrogenase↗

PubMed1991

Urinary excretion of acetylcyanamide in rat and human after oral and dermal application of hydrogen cyanamide (H2NCN).

The main urinary metabolite of hydrogen cyanamide (syn.: cyanamide) in rat and man is acetylcyanamide (syn.: N-acetylcyanamide). An analytical method was developed to determine acetylcyanamide in the urine with a limit of quantification of less than 10 micrograms/l (mean recovery 96.1% using spikes of 20 micrograms/l; relative standard deviation less than 4%). This methodology is based upon ion chromatography using column-switch techniques and UV detection. It could be demonstrated that in rats an average of 45.6% of oral applied cyanamide (10 mg/kg) was excreted in the urine as acetylcyanamide. In male human volunteers a mean of 40% of oral administered cyanamide (mean dose 0.25 mg/kg body weight) was excreted via the urine as acetylcyanamide. The same group of volunteers participated in a skin absorption study with dermal application of the above cyanamide dose onto a skin surface area of 32 cm2. Within an application period of 6 h an average cyanamide quantity of 2.3 mg was available for skin absorption. A mean portion of 7.7% of this quantity was found as acetylcyanamide in the urine of the participants. Findings from literature state that cyanamide is metabolized in vitro to cyanide. According to examinations performed in vivo, however, such a metabolic pathway seems to be irrelevant for man. In comparison with the control values there was no significant increase of both the cyanide concentrations in the blood and the thiocyanate concentrations in the urine of the above volunteers after the described oral cyanamide administration.

Administration, Oral↗

PubMed1984

Effect of acetaldehyde and cyanamide on the metabolism of formaldehyde by hepatocytes, mitochondria, and soluble supernatant from rat liver.

Formaldehyde can be metabolized primarily by two different pathways, one involving oxidation by the low-Km mitochondrial aldehyde dehydrogenase, the other involving a specific, glutathione-dependent, formaldehyde dehydrogenase. To estimate the roles played by each enzyme in formaldehyde metabolism by rat hepatocytes, experiments with acetaldehyde and cyanamide, a potent inhibitor of the low-Km aldehyde dehydrogenase were carried out. The glutathione-dependent oxidation of formaldehyde by 100,000g rat liver supernatant fractions was not affected by either acetaldehyde or by cyanamide. By contrast, the uptake of formaldehyde by intact mitochondria was inhibited 75 to 90% by cyanamide. Acetaldehyde inhibited the uptake of formaldehyde by mitochondria in a competitive fashion. Formaldehyde was a weak inhibitor of the oxidation of acetaldehyde by mitochondria, suggesting that, relative to formaldehyde, acetaldehyde was a preferred substrate. In isolated hepatocytes, cyanamide, which inhibited the oxidation of acetaldehyde by 75 to 90%, produced only 30 to 50% inhibition of formaldehyde uptake by cells as well as of the production of 14CO2 and of formate from [14C]formaldehyde. The extent of inhibition by cyanamide was the same as that produced by acetaldehyde (30-40%). In the presence of cyanamide, acetaldehyde was no longer inhibitory, suggesting that acetaldehyde and cyanamide may act at the same site(s) and inhibit the same formaldehyde-oxidizing enzyme system. These results suggest that, in rat hepatocytes, formaldehyde is oxidized by cyanamide- and acetaldehyde-sensitive (low-Km aldehyde dehydrogenase) and insensitive (formaldehyde dehydrogenase) reactions, and that both enzymes appear to contribute about equally toward the overall metabolism of formaldehyde.

Acetaldehyde↗

PubMed1989

Inactivation of low-Km rat liver mitochondrial aldehyde dehydrogenase by cyanamide in vitro. A catalase-mediated reaction.

The inactivation of the affinity chromatography purified low-Km rat liver mitochondrial aldehyde dehydrogenase (ALDH)--free of catalase activity--by the alcohol sensitizing agent cyanamide was studied in vitro. This ALDH-purified preparation was not susceptible to cyanamide inactivation at concentrations up to 2.5 mM. On the other hand, ALDH activity appears to be irreversibly inhibited when the incubation mixture contained ALDH, catalase, NAD+ and cyanamide. Influence of catalase, NAD+ and cyanamide concentrations in the incubation mixtures on the ALDH activity were also established. The time course of the concentration of cyanamide in an incubation mixture when ALDH activity was inhibited by cyanamide in the presence of catalase and NAD+, was evaluated by HPLC. No disappearance of cyanamide was observed for a period of time up to 24 hr. This result suggests that no metabolic conversion of cyanamide to an active inhibitory form takes place, as has been suggested recently.

Aldehyde Dehydrogenase↗

PubMed1981

The effect of cyanamide on acetaldehyde oxidation by isolated rat liver mitochondria and on the inhibition of pyruvate oxidation by acetaldehyde.

Compared to other substrates, the oxidation of pyruvate by isolated mitochondria is especially sensitive to inhibition by acetaldehyde. It is not known whether this inhibition represents a direct effect of acetaldehyde or requires the metabolism of acetaldehyde. Experiments were therefore carried out in the presence of cyanamide, an inhibitor of aldehyde dehydrogenase. After a brief incubation period, cyanamide inhibited the state 4 and state 3 rate of acetaldehyde (0.1-1.0 mM) oxidation by isolated rat liver mitochondria. Little inhibition was found in the absence of the incubation period. Maximum inhibition was found at cyanamide concentrations of 0.01 to 0.033 mM. Cyanamide also inhibited the activity of aldehyde dehydrogenase assayed in disrupted mitochondrial fractions. The inhibition by cyanamide was specific since cyanamide did not affect mitochondrial oxidation of succinate, glutamate, or pyruvate. Acetaldehyde inhibited the state 3 rate of pyruvate oxidation by liver mitochondria. Despite preventing acetaldehyde oxidation, cyanamide did not prevent the inhibition of pyruvate oxidation by acetaldehyde. These results indicate that (a) cyanamide can be used as an effective in vitro inhibitor of acetaldehyde oxidation and (b) the unique sensitivity of pyruvate oxidation to acetaldehyde represents a direct effect of acetaldehyde on pyruvate dehydrogenase.

Acetaldehyde↗

PubMed1989

Effect of cyanamide on transaminases and other serum proteins in the rat.

The changes of the serum biochemical features induced by cyanamide, a drug used in the pharmacological treatment of alcoholism, were studied in Wistar rats. Sixty five Wistar rats were divided into 6 groups, 4 experimental and 2 control. Two experimental groups received cyanamide intraperitoneally, at a dose of 1 and 16 mg per kg of body weight, for 8 weeks. One experimental group received CCl4 and the other one CCl4 and cyanamide for 13 weeks. In addition to a delay in the increase of body weight as compared with the control group, the rats receiving cyanamide underwent a marked dispersion of the transaminase and LDH values. This could be explained by the double effect of cyanamide: its capacity to depress the cellular activity (lowered synthesis of proteins, transaminase and LDH among them) and cellular damage. Therefore, some animals showed a marked depression of protein synthesis, causing low enzyme values while cytolysis prevailed in the rest as seen in higher enzyme values. When cyanamide and CCl4 were employed simultaneously, the cyanamide tended to diminish the higher enzyme values caused by CCl4 when used alone. These findings can explain why patients on cyanamide may develop severe liver damage without serious alterations in tests for liver function.

Alanine Transaminase↗

PubMed1984

The metabolic activation of cyanamide to an inhibitor of aldehyde dehydrogenase is catalyzed by catalase.

The inhibition of aldehyde dehydrogenase by cyanamide is dependent on an enzyme catalyzed conversion of the latter to an active metabolite. The following results suggest that catalase is the enzyme responsible for this bioactivation. The elevation of blood acetaldehyde elicited by cyanamide after ethanol administration to rats was attenuated more than 90 percent by pretreatment with the catalase inhibitor, 3-amino-1,2,4-triazole. This attenuation was dose dependent and was accompanied by a reduction in total hepatic catalase activity. Although hepatic catalase was also inhibited by cyanamide, a positive correlation between blood acetaldehyde and hepatic catalase activity was observed. In vitro, the activation inhibitor, 3-amino-1,2,4-triazole. This attenuation was dose dependent and was accompanied by a reduction in total hepatic catalase activity. Although hepatic catalase was also inhibited by cyanamide, a positive correlation between blood acetaldehyde and hepatic catalase activity was observed. In vitro, the activation of cyanamide was catalyzed by a) the rat liver mitochondrial subcellular fraction, b) the 50-65% ammonium sulfate mitochondrial fraction and c) purified bovine liver catalase. Cyanamide activation was inhibited by sodium azide. Since much of the hepatic catalase is localized in the peroxisomes and since peroxisomes and mitochondria cosediment, the cyanamide activating enzyme, catalase, is likely of peroxisomal and mitochondrial origin.

Acetaldehyde↗

PubMed1983

Potentiation of ethanol toxicity by cyanamide in relation to acetaldehyde accumulation.

The possibility that acetaldehyde accumulation potentiates the acute toxicity of ethanol was studied by pretreating rats with cyanamide, an aldehyde dehydrogenase inhibitor. At 30 min after administration of ethanol (7 to 9 g/kg, po), the levels of acetaldehyde in femoral venous blood of cyanamide-treated rats were increased from 10 to 20 to 600 mumol/liter and at death the concentrations of acetaldehyde in heart blood and cerebrospinal fluid were still 7 to 9 and 4 to 9 times higher, respectively, than in rats given ethanol only. The cyanamide pretreatment (25 mg/kg) significantly increased the mortality of rats given 6.5 to 7.0 g/kg ethanol and decreased the LD50 of ethanol from 7.3 to 5.9 g/kg. Cyanamide increased the late mortality, possibly because of sustained acetaldehyde accumulation. Although administration of the alcohol dehydrogenase inhibitor, 4-methylpyrazole (4-MP, 10 mg/kg), prevented the accumulation of acetaldehyde, it only partly counteracted the effect of cyanamide on mortality. After coadministration of cyanamide and 4-MP, the LD50 of ethanol was 6.5 g/kg, and after 4-MP alone, 6.7 g/kg. 4-MP by itself seemed to increase the early mortality of rats to ethanol poisoning. The results suggest that the potentiating effect of cyanamide on ethanol toxicity can partly be explained by acetaldehyde accumulation and that 4-MP can be used to inhibit this accumulation providing its central depressant effect is taken into account.

Acetaldehyde↗

PubMedDate not supplied

N-acetylcyanamide, the major urinary metabolite of cyanamide in rat, rabbit, dog, and man.

The structure of the major urinary metabolite of cyanamide, the active component of the alcohol deterrent agents Temposil , Dipsan , and Abstem , in rats, rabbits, and dogs has been established as N- acetylcyanamide by its identity with chemically synthesized N- acetylcyanamide , and by conversion of the metabolite and the synthetic product to identical derivatives, viz. to N-benzyl-N- acetylcyanamide and to N-(p-nitrobenzyl)-N- acetylcyanamide . The latter derivatives were analyzed by pulsed positive/negative ion chemical ionization mass spectroscopy. Urine from patients receiving cyanamide as a treatment mode was shown to contain N- acetylcyanamide by chemical ionization mass spectrometric analysis of the isolated p-nitrobenzyl derivative, thereby establishing that N- acetylcyanamide is also a metabolite in man. The major portion (87%) of the first 27-hr urinary radioactivity excreted by the dog after receiving a low dose of [14C]cyanamide (0.04 mmol/kg, po) was N- acetylcyanamide , as determined by inverse isotope dilution and measurement of the specific radioactivity of its N-p-nitrobenzyl derivative. This indicates that at low doses acetylation is also a major route of biotransformation of cyanamide in the dog. Hepatic N-acetyltransferase, isolated from the rabbit and dog, catalyzed the transfer of the acetyl group from acetyl-S-CoA to [14C]cyanamide producing N-acetyl[14C]cyanamide. The enzyme isolated from the liver of a rapid acetylator phenotype rabbit was twice as effective as the dog enzyme in catalyzing this transfer. Thus, the enzyme responsible for this biotransformation of cyanamide is an acetyl-S-CoA-dependent N-acetyltransferase.

Acetylation↗

PubMed1976

[The influence of straw, particularly rice straw, together with calcium-cyanamide on the microbiological activity of two Portuguese soils (author's transl)].

The influence of calcium-cyanamide upon the microbiological activity was tested in pot experiments under controlled conditions in two Portuguese soils (sandy and loamy) after the addition of rice or wheat straw (rice straw 0.275% N, wheat straw 0.307% N). The amount of straw was equalled to 100 dz/ha, the application of calcium-cyanamide to 25, 50 and 100 kg N/ha. In the containers treated with straw the total amount of microorganisms (Koch-method) was higher in sandy than in loamy soil after 30 days, but after 70 days it was higher in loamy soil. The content of active nitrogen (NH4 + NO3) increased, when calcium-cyanamide was added, but decreased after the application of straw. After 70 days sandy soil again showed an increase of active nitrogen. Straw increased the rates of CO2-production considerably, wheat straw was superior to rice straw. Calcium-cyanamide increased the CO2-production more in sandy than in loamy soil or German loess, which was also used for this experiment. Only in the case of rice straw higher doses of calcium-cyanamide had a positive effect. After 70 days the CO2-production rose only when rice straw was applied. The dehydrogenase-activity was increased in both soils, but a superiority of wheat straw occurred in sandy soil only. The microbiological activity in the pots with straw was higher in sandy than in loamy soil, the addition of calcium-cyanamide accelerated it. Doses of 25-50 kg N/ha are sufficient generally. The period of the formation of insoluble organic N-compounds, usually connected with the application of organic matter with a wide N:C-ratio, seems to be reduced by the addition of calcium-cyanamide.

Actinomycetales↗

PubMed1981

Cyanamide mediated syntheses of peptides containing histidine and hydrophobic amino acids.

Using the model of a primitive earth evaporation pond, the synthesis of three histidyl peptides in yields up to 11% was demonstrated when aqueous solutions of histidine, leucine, ATP, cyanamide, and MgCl2 were evaporated and heated for 24 h at 80 degrees C. In addition, peptides were formed in yields of up to 56%, 35%, and 21%, respectively for phenylalanine, leucine, and alanine when aqueous solutions of the appropriate amino acid were evaporated and heated with cyanamide and one or more of the following components: ATP, AMP, 4-amino-5-imidazole carboxamide, or MgCl2. The greatest peptide yield occurred at pH 3. But peptide formation was demonstrated for a system of Leu, cyanamide, and MgCl2 adjusted to pH 7 with NH4OH. Peptide synthesis was also studied in the presence of CaCl2, ZnCl2, different adenosine nucleotides, and UTP to compare their effects on peptide synthesis. The optimum conditions for cyanamide mediated peptide synthesis were also studied in terms of pH, reaction time, reaction temperature, and cyanamide concentration. The major side product in nearly all reactions studied appears to be an amino acid-cyanamide adduct. Peptides were analyzed and identified by thin layer chromatography, acid hydrolysis, and enzymatic degradation.

Amino Acids↗

PubMed1986

Differential inhibition of rat tissue catalase by cyanamide.

The relative sensitivity of rat tissue catalase to inhibition by intraperitoneally administered cyanamide was liver greater than kidney greater than heart greater than brain, whereas the activity of the erythrocyte enzyme was affected minimally. The measured ED50 values for cyanamide in these tissues were 31, 44, 107 and 680 mumoles/kg body weight for liver, kidney, heart and brain respectively. On a molar basis, cyanamide was approximately twenty times more potent than 3-amino-1,2,4-triazole (3-AT) in inhibiting hepatic catalase in vivo in the rat. Like 3-AT, cyanamide inhibited erythrocyte catalase activity in vitro in the presence of hydrogen peroxide. The apparent similarities between the inhibition of hepatic catalase by cyanamide and 3-AT in vivo suggest that cyanamide belongs to the family of 3-AT-like catalase inhibitors.

Amitrole↗

PubMed1986

Effects of cyanamide on body weight and brain monoamines and metabolites in rats.

Cyanamide, a disulfiram-like drug used in the treatment of alcoholism, decreased in a dose-dependent manner (2-25 mg/kg) the body weight gain curve in rats, which resulted in a marked decrease of body weight (10-35%). Long-term administration of cyanamide also decreased food intake (6-34%) in a dose-dependent manner (2-25 mg/kg). Both effects of cyanamide were reversible. After the acute and long-term administration (1-12 months) of cyanamide (8-35 mg/kg) the brain concentration of 3-methoxy-4-hydroxyphenylethyleneglycol sulphate (MOPEG-SO4) was also significantly increased (26-46%). Cyanamide, however, had no effects on the brain concentration of noradrenaline, dopamine, 5-hydroxytryptamine, tryptophan and 5-hydroxyindolacetic acid. It is suggested that the loss of weight, the decrease in food intake and the increase in brain MOPEG-SO4 induced by cyanamide reflect possible anorectic properties of the drug.

Animals↗

PubMed1986

Acyl, N-protected alpha-aminoacyl, and peptidyl derivatives as prodrug forms of the alcohol deterrent agent cyanamide.

Cyanamide (H2NC identical to N), a potent aldehyde dehydrogenase (AlDH) inhibitor that is used therapeutically as an alcohol deterrent agent, is known to be rapidly metabolized and excreted in the urine as acetylcyanamide (1). On the basis of our observation that 1 is deacetylated to cyanamide in vivo, albeit very slightly, thereby serving as a precursor of prodrug form of the latter, several acyl derivatives of cyanamide were synthesized specifically as prodrugs, including benzoylcyanamide (2), pivaloylcyanamide (3), and 1-adamantoylcyanamide (4), as well as long- and medium-chain fatty acyl derivatives such as palmitoyl- (6), stearoyl- (7), and n-butyrylcyanamide (5). N-Protected alpha-aminoacyl and peptidyl derivatives of cyanamide were also synthesized, and these include N-carbobenzoxyglycyl- (10), hippuryl- (13), N-benzoyl-L-leucyl- (14), N-carbobenzoxyglycyl-L-leucyl- (18), N-carbobenzoxy-L-pyroglutamyl- (22), L-pyroglutamyl-L-leucyl- (19), and L-pyroglutamyl-L-phenylalanylcyanamide (20). All of these prodrugs of cyanamide raised ethanol-derived blood acetaldehyde levels in rats significantly over controls 3 h after ip drug administration, and some of these were still capable of elevating blood acetaldehyde 16 h post drug administration. A selected group of cyanamide prodrugs were also evaluated by the oral route of administration and showed nearly equivalent activity as the ip route in elevating ethanol-derived blood acetaldehyde. These results suggest potential utility of these prodrugs as deterrent agents for the treatment of alcoholism.

Acylation↗

PubMedDate not supplied

Inactivation mechanism of low-KM rat liver mitochondrial aldehyde dehydrogenase by cyanamide in vitro.

The inactivation of low-KM rat liver mitochondrial aldehyde dehydrogenase (ALDH) by the alcohol-sensitizing agent cyanamide (H2NCN) has been studied in vitro. The effect of the concentrations of NAD+ at different concentrations of catalase on the inactivation of ALDH by cyanamide (20 and 200 microM) in vitro point to an ALDH-NAD(+)-catalase complex prior to the binding to cyanamide to form the holoenzyme-inhibitor complex. Cyanamide itself could be responsible for the inactivation of ALDH. The possibility that both irreversibly inactivated ALDH and cyanamide remain free at the end of the inactivation process is discussed. The effects of pH and ionic strength on the inactivation process are also described. The pseudo-first order rate constants for inactivation of low-KM ALDH depends on both effects, suggesting that electrostatic forces are involved in the process and that a group with pK approximately 6.8, presumably a histidine residue, at the active site of ALDH could be involved. A representative equation for the inactivation process of low-KM ALDH by cyanamide in vitro has been fitted to experimental kinetic data, involving both catalase and inhibitor concentrations.

Aldehyde Dehydrogenase↗

PubMed1987

Metabolism of cyanamide to cyanide and an inhibitor of aldehyde dehydrogenase (ALDH) by rat liver microsomes.

Rat liver microsomes, as well as purified catalase, convert the alcohol deterrent agent, cyanamide, to an active inhibitor of AlDH. Whether this enzymatic activation of cyanamide is mediated primarily by catalase present in the microsomes or involves the cytochrome P-450 enzymes is not known. We now report that cyanide is also a product of the microsomal oxidation of cyanamide. Formation of cyanide from cyanamide and rat liver microsomes was time dependent, reaching maximal levels within 5-10 min. Induction of the cytochrome P-450 enzymes by phenobarbital (PB) pretreatment doubled the yield of cyanide, while SKF-525A blocked this PB-induced increase. Administration of 3-aminotriazole (3-AT) to PB-treated rats inhibited the catalatic activity of their microsomes by 98% and substantially reduced cyanide formation. These results suggest that while catalase is responsible in major part for the oxidation of cyanamide to cyanide by uninduced microsomes, the participation of the hepatic cytochrome P-450 enzymes cannot be ruled out in PB-induced microsomes. We propose a metabolic scheme wherein N-hydroxycyanamide is the intermediate product of cyanamide oxidation, which then decomposes to yield the observed product, cyanide. By deduction, the second product of this decomposition is postulated to be nitroxyl (HNO), which may be the active AlDH inhibitor.

Aldehyde Dehydrogenase↗