Oxalic acid metabolite

Bromophenol blue (3.0...4.6) aliphatic carboxylic acids [225 — 228] malonic and lactic acids [229] palmitic and lactic acids [230] malonic, glycolic, malic, citric, tartaric, ketoglutaric, galacturonic and oxalic acids [196] dicarboxylic acids, succinic acid [231] indoleacetic acid, trichloroacetic acid [232] palmitic acid, palmityl- and stearyllactic acid [223] benzoic, sorbic and salicylic acid [234] metabolites of ascorbic acid [235] chloropropionic acid [236] oligogalacturonic acids [237] amino acids, hydrocarbons, mono-, di- and triglycerides [238] xylobiose, xylose, glucose and derivatives [239] sugar alcohols [91] toxaphene [240]... 

A. niger normally produces many useful secondary metabolites citric and oxalic acids are stated as the dominant products. Limitation of phosphate and certain metals such as copper, iron and manganese results in a predominant yield of citric acid. The additional iron may act as a cofactor for an enzyme that uses citric acid as a substrate in the TCA cycle as a result, intermediates of the TCA cycle are formed. 

ADH also has clinical significance in the metabolism of methanol and ethylene glycol, two drugs with toxic metabolites. Methanol is oxidized by ADH to formaldehyde, which damages the retina and can cause blindness. Ethylene glycol is metabohzed by ADH to oxalic acid, which has renal tox-... 

Plant. Picloram degraded very slowly in cotton plants releasing carbon dioxide (Meikle et al., 1966). Metabolites identified in spring wheat were 4-amino-2,3,5-trichloropyridine, oxalic acid, and 4-amino-3,5-dichloro-6-hydroxypicolinic acid (Redemann et al., 1968 Plimmer, 1970). In soil, 4-amino-3,5-dichloro-6-hydroxypicolinic acid was the only compound positively identified (Redemann et al., 1968). 

Ethylene glycol is rapidly metabolised to glyco-laldehyde, then glycolic acid, glyoxylic acid and finally to oxalic acid. The metabolites are toxic to kidneys, brain and heart. 

Three stages of ethylene glycol overdose occur. Within the first few hours after ingestion, there is transient excitation followed by CNS depression. After a delay of 4-12 hours, severe metabolic acidosis develops from accumulation of acid metabolites and lactate. Finally, delayed renal insufficiency follows deposition of oxalate in renal tubules. The key to the diagnosis of ethylene glycol poisoning is recognition of anion gap acidosis, osmolar gap, and oxalate crystals in the urine in a patient without visual symptoms. 

The mechanism of toxicity of ethylene glycol involves metabolism, but unlike previous examples, this does not involve metabolic activation to a reactive metabolite. Thus, ethylene glycol is metabolized by several oxidation steps eventually to yield oxalic acid (Fig. 7.84). The first step is catalyzed by the enzyme alcohol dehydrogenase, and herein lies the key to treatment of poisoning. The result of each of the metabolic steps is the production of NADH. The imbalance in the level of this in the body is adjusted by oxidation to NAD coupled to the production of lactate. There is thus an increase in the level of lactate, and lactic acidosis may result. Also, the intermediate metabolites of ethylene glycol have metabolic effects such as the inhibition of oxidative phosphorylation, glucose metabolism, Krebs cycle, protein synthesis, RNA synthesis, and DNA replication. 

Trichloroethane is rapidly absorbed after inhalation, oral administration and application to the skin in rodents. 1,1,2-Trichloroethane is extensively metabolized in mice given 100-200 mg/kg bw by intraperitoneal injection, 73-87 % of the dose being eliminated in the urine and 16-22% in expired air. Several urinary metabolites have been identified chloroacetic acid, S-carboxymethyl-i,-cysteine, thiodiacetic acid, 2,2-dichloroethanol and oxalic acid (lARC, 1991). 

An HPLC assay was described as a routine method for the determination of FLU and its hydroxylated metabolite 7-OH FLU in pig kidney tissues (188). The sample was extracted with ethyl acetate after evaporation, the residue was dissolved in MeCN-oxalic acid (1 1). Analytical separation was performed using fluorimetric detection under gradient elution. The authors recommended an Ultrabase C-18 column, which allowed the work to be carried out at extreme pH values, ranging from 2 to 8. The assay was specific and reproducible within the range 50-2500 yug/kg recovery was 94.8%. 

Disposition in the Body. Less than 5% of ingested oxalic acid is absorbed in healthy adults. About 8 to 40 mg of oxalic acid is normally excreted in the urine daily this is derived mainly from the metabolism of dietary ascorbic acid and glycine with small amounts from dietary oxalic acid and other minor metabolic sources. Calcium oxalate is a major constituent of kidney stones and is frequently found as crystals in freshly-voided urine. In normal subjects concentrations of oxalic acid in blood range from about 1 to 3 pg/ml. Small amounts of oxalate are produced as a metabolite of ethylene glycol. 

As a result of GC-MS analyses, 103 metabolites were determined, of which 66 were successfully identified and 18 were used to create a diagnostic model. Of these 18 metabolites, 5 (suberic acid, glycine, L-tyrosine, L-threonine, and succinic acid) had significantly higher levels in patients with HCC than in healthy volunteers (p < 0.05). Other metabolites (oxalic acid, xylitol, urea, phosphates, propanoic acid, threonine, pimelic acid, butyric acid, trihydroxypentanoic acid, hypoxanthine, arabinofuranose, dipeptide of hydroxyproline, and tetrahydroxypentanoic acid) showed higher levels in healthy volunteers (p < 0.05). In addition, Wu et al. determined the levels of AFP using an ELISA test in serum from the same patients and healthy volunteers as in the metabolomic study of urine samples. An AFP concentration above 20 ng/mL suggests a positive result and the presence of... 

At the dawn of the twentieth century, only a few simple fermentation products such as oxalic acid and citric acid had been isolated from the lower fungi. Soon after World War I, Harold Raistrick initiated the first systematic studies of the chemistry of mould metabolites and in the course of the following four decades made a seminal contribution to the recognition of fiingi as a major source of natural products. ... 

Ascorbic acid is readily absorbed by an active process. Large doses can saturate this system, limiting the amounts absorbed. Once absorbed, it is distributed to all tissue. The vitamin is metabolized to oxalic acid before excretion. Ascorbic acid-2-sulfatc is also a metabolite found in the urine. Large doses result in the excretion of substantial amounts of unchanged ascorbic acid. The resultant acidification of the urine is the basis for most of the vitamin s adverse effects. 

Ethylene glycol and glycoaldehyde have an intoxicating effect on the central nervous system that can lead to ataxia, sedation, coma, and respiratory arrest. The metabolic acidosis reported in toxicity is due to the acidic metabolites, especially glycolic acid. Ethylene glycol itself may result in a large osmolar gap. Oxalic acid may combine with calcium to form calcium oxylate crystals. The precipitation of these crystals in tissue may result in renal failure and hypocalcemia. 

When introduced via the oral or inhalation routes, tetrachloroethane is metabolized primarily to tri-chloroethanol, trichloroacetic acids that are subsequently broken down to glyoxylic acid, oxalic acid and carbon dioxide and are excreted chiefly as metabolites in the breath and urine. A small amount is expired in the breath as carbon dioxide and as the parent compound. 

Metabolism is saturable and relatively slow with only a small percentage of the administered dose excreted as metabolites, the major one being trichloroacetic acid. Following exposure to PERC, trichloroacetic acid, and trichloroethanol have been found in the urine of humans and animals. Additionally, oxalic acid, dichloroacetic acid, and ethylene glycol have been reported in the urine of exposed animals. Other reported biotransformation products include inorganic chlorine and ra s-l,2-dichloro-ethylene in expired air. 

Ethylene glycol, present in antifreeze products, may be ingested accidentally or for the purpose of inebriation or suicide. Ethylene glycol itself is relatively nontoxic, and its initial CNS effects resemble those of ethanol. However, metabolism of ethylene glycol by ADH results in the formation of a number of acid metabolites, including oxalic acid and glycolic acid (Figure 34-16). 

Ingested ethylene glycol is metabolized to glycolic and oxalic acids and other acidic metabolites. Its metabolism leads to an acidosis with high anion and osmolal gaps. Accumulation of toxic metabohtes may contribute to lactic acid production that further contributes to the acidosis. Precipitation of calcium oxalate and hippurate crystals in the urinary tract... 

The mechanism of toxicity of ethylene glycol involves metabolism, but unlike previous examples this does not involve metabolic activation to a reactive metabolite. Thus, ethylene glycol is metabolized by several oxidation steps eventually to yield oxalic acid (figure 7,56). The first step is catalysed by the... 

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