Mandelic acid metabolite

Fig. 11.12. Metabolic scheme for reaction of benzyl cyanide (11.80) to mandelonitrile (11.81) as a crossroads to benzoic acid (11.83) via oxidative denitrilation, and to mandelic acid (11.82) as a minor metabolite produced by hydrolysis of the CN group [118][122]...

To elucidate the metabolic pathway of phenylmalonic acid, the incubation broth of A. bronchisepticus on phenylmalonic acid was examined at the early stage of cultivation. After a one-day incubation period, phenylmalonic acid was recovered in 80% yield. It is worthy of note that the supposed intermediate, mandelic acid, was obtained in 1.4% yield, as shown in Eq. (8). The absolute configuration of this oxidation product was revealed to be S. After 2 days, no metabolite was recovered from the broth. It is highly probable that the intermediary mandelic acid is further oxidized via benzoylformic acid. As the isolated mandelic acid is optically active, the enzyme responsible for the oxidation of the acid is assumed to be S-specific. If this assumption is correct, the enzyme should leave the intact l -enantiomer behind when a racemic mixture of mandelic acid is subjected to the reaction. This expectation was nicely realized by adding the racemate of mandelic acid to a suspension of A. bronchisepticus after a 4-day incubation [4]. 

When the resulting mixture of benzoylformic acid and (i )-mandelic acid was treated with a cell free extract of Streptomyces faecalis IFO 12964 in the presence of NADH,the keto acid can be effectively reduced to (i )-mandelic acid (Fig. 1). Fortunately the presence of A. bronchisepticus and its metabolite had no influence on the reduction of the keto acid. The regeneration of NADH was nicely achieved by coupling the reaction with reduction by formic acid with the aid of formate dehydrogenase. As a whole, the total conversion of racemic mandelic acid to the i -enantiomer proceeded with very high chemical and optical yields. The method is very simple and can be performed in a one-pot procedure [6]. 

Valko et al. (22) studied the separation of mandelic acid enantiomers with y-CD and calculated very low binding constants 2.8 and 2.4 M x for the d- and L-enantiomers, respectively. The weak binding of mandelic acid to y-CD was explained by the large size of the y-CD torus for such a small molecule as mandelic acid. Unlike the enantiomers of leucovorin and its active metabolite, for which weak binding was associated with low enantio-selective (19), fairly high enantioselectivity was found for weakly bonded enantiomers of mandelic acid with y-CD (KD/KL = 1.17). 

Other metabolites that may be formed from aryl solvent precursors include mandelic acid and phenylgloxylic acid. 

Indoleacetic acid is a metabolite of serotonin. Homo vanillic acid is a metabolite of dopamine and vanillin mandelic acid of epinephrine and norepinephrine. 

This stimulant has been reported frequently in man and occasionally in horses. Although moderate concentrations of pemoline may be detected using Screen B (p. 91), for greater sensitivity the concentration of the metabolite, mandelic acid, should be determined using gas chromatography-mass spec-trometry confirmatory tests for pemoline should also be carried out since mandelic acid is a metabolite of several compounds. 

Disposition in the Body. Readily absorbed after oral administration. Metabolised by A-dealkylation, reduction, deamination, and A-hydroxylation primarily to active metabolites keto-reduction is stereoselective resulting in the formation of threo-hydroxylated metabolites glucuronide formation also occurs along with the formation of hippuric and mandelic acids. About 80 to 90% of a dose is excreted in the urine the amount excreted in the urine is reduced when the urine is alkaline of the urinary excreted material, A-ethylaminopropiophenone, norephedrine (phenylpropanolamine), and hippuric acid are the main metabolites together with small amounts of unchanged drug, amino-propiophenone, A-diethylnorephedrine, and A-ethylnor-ephedrine. 

Disposition in the Body. Rapidly distributed after intravenous injection. It is metabolised in the liver by hydrolysis and N-dealkylation to inactive metabolites. About 90% of a dose is excreted in the urine as the carboxylic acid derivative, together with mandelic acid and benzoic acid less than 5% is excreted as unchanged drug. 

Disposition in the Body. Mandelic acid is a urinary metabolite of several drugs and toxic chemicals and is also found endogenously in normal urine at concentrations of up to 5 pg/ml. 

Disposition in the Body. Slowly absorbed after oral administration. About 50% of a dose is excreted in the urine as unchanged drug in 48 hours and about 4% as 5-phenyloxazolidine-2,4-dione the remainder is excreted in the urine as conjugated pemoline and unidentified polar metabolites mandelic acid is also a metabolite of pemoline. Less than 1% of a dose is eliminated in the faeces. 

Ethyl benzene distributes to the adipose tissues. It is metabolized to mandelic acid (64%) and phenyl-glyoxylic acid (25%). The percentage of metabolites may vary according to the route of exposure with mandelic acid formation being favored with inhalation. The primary route of excretion is via the urine. Experimental evidence indicates that the percutaneous absorption rate of ethyl benzene is 37 pgcm... 

Tetrachlorvinphos is readily absorbed through the gastrointestinal tract following oral exposure. Major metabolites following oral exposure in rats and dogs include desmethyl tetrachlorvinphos, 2,4,5-trichlor-ophenylethandiol glucuronide, and 2,4,5-trichloro-mandelic acid. Metabolism and excretion of radioactive tetrachlorvinphos in rats is rapid and majority of radioactivity appears between 0 and 24 h of exposure in urine and feces. 

A16. Armstrong, M. D., McMillan, A., and Shaw, K. N. F., 3-Methoxy-4-hydroxy-D-mandelic acid, a urinary metabolite of norepinephrine. Biochim. et Biophus. Acta 26, 422 (1957). 

Benzphetamine is a methamphetamine whose tertiary amine also carries a benzyl group. The likelihood of metabolic N-debenzylation yielding methamphetamine would, of course, explain its effects. Diethylpropion (No. 14) is an interesting compound because of its particularly involved metabolic degradation, which is initiated by stepwise N-deethylation and keto reduction to a P-OH. These active metabolites, presumably with the parent compound, explain both anorexiant and CNS effects, as well as the reduced level of the latter when compared with amphetamine. Subsequent oxidations all the way to benzoic, hydrox-ybenzoic, and mandelic acids all lead to inactivation. 

The oral toxicity in animals was found to be low to very low. An LD50 value of 3500 mg/kg for rats has been documented (NIOSH 1986). No adverse effects were noted in animals subjected to chronic inhalation exposure at below 400 ppm. At higher dosages only the liver was affected (ACGIH 1986). Ethyl benzene is eliminated from the body by metabolic excretion. The urinary metabolites in humans are mainly mandelic acid, C6HsCH(OH)COOH, and benzoyl-formic acid, CeHsCOCOOH. 

Mandelic acid and benzoylformic acid are the major urinary metabolites. However, the excretion of mandelic acid was less when styrene was absorbed through the skin. 

Styrene may be analyzed by GC, nsing a flame ionization detector. Air analysis may be performed by charcoal adsorption, followed by desorption of the analyte with carbon disnl-fide and injection of the elnant into GC-FID (NIOSH Method 1501 see Section 26.2). Styrene intake in the body may be estimated by analyzing mandelic acid in the nrine by liquid chromatography, polarography, or GC. However, the presence of other aromatics may interfere, as these componnds also generate the same urinary metabolite. Styrene in exhaled air may be analyzed by absorption over ethanol or charcoal followed by GC, UV, or IR analysis. 

The metabolites of cyclandelate are mandelic acid, phenylglyoxylic acid and 3,3,5-trimethylcyclohexanol. These are detectable in the urine of rabbits and humans in less than two hours after oral administration (19,20). The ratio of mandelic acid to phenylglyoxylic acid increases with increased dosage (21). Another metabolic study in humans showed that the maximum blood levels of mandelic acid were reached in 0.5 to 1.5 hours after oral dosing (22). 

Traces of styrene can affect the quality of food products above certain migration levels. It has been shown that usually over half of the residual styrene in the food contact packaging material migrates within 24 hours, which is the normal shelf life of many food products. The metabolites of styrene are mandelic acid, a known mutagen, and styrene oxide, a known carcinogen. 

Urinary metabolite(s) Mandelic acid (MA), Phenvlglvoxvlic acid (PA) Trichloroacetic acid (TCA)... 

Catecholamines and their metabolites The catecholamines, adrenaline, noradrenaline, and dopamine are essential components of the central nervous system acting as neurotransmitters both within the brain and at peripheral nerves. All are synthesized in the adrenal medulla from phenylalanine or tyrosine and are metabolized by a mixture of enzymatic side chain oxidation and methylation of the hydroxy groups on the ring. If the metabolism is complete, adrenaline and noradrenaline are degraded to 4-hydroxy-3-methoxy mandelic acid (HMMA, commonly called vanillylmandelic acid - VMA), while dopamine is broken down to homovanillic acid (HVA). Urinary excretion of these metabolites and their conjugates is the major route of elimination of catecholamines from the body, although small amounts are excreted unchanged as the free catecholamines. 

Mandelic acid, a major metabolite of cyclandel-ate [3,3,5-trimethylcyclohexyl)-mandelate], is a very effective hydroxyl radical scavenger (Haenen 1989). 

Catechol-O-methyltransferase from rat liver requires S-adeno-sylmethionine as a methyl donor and can methylate catechol but not monohydroxy derivatives of phenylethylamine. In vivo, O-methylation occurs exclusively in the meta position to the carbon side chain, but with purified preparations of the enzyme in vitro methylation can lead to both meta and para methylation. The ratio of products is susceptible. to both the polarity of the substrate and the pH of the medium . In man 3-methoxy-4-hydroxy-mandelic acid (18) comprises about 40 per cent of the total urinary metabolites produced from the catecholamines whilst in other pecies 3-methoxy-4-hydroxyphenylglycol (19), isolated as a sulphate ester, is the predominant breakdown product . A typical metabolic grid which indicates the possible types of pathway leading from noradrenalin (17) to both of these metabolites is shown in Figure 4.4 analogous metabolic schemes may be drawn up for both adrenalin and dopamine. 

MAO within adrenergic nerves is apparently involved in the control of the steady-state concentration of NA, both in the CNS and in sympathetic nerves. Inhibition of MAO may increase the NA content of tissues to several times that found under normal conditions. Intraneuronal MAO is also responsible for the degradation of catecholamines released from storage vesicles by reserpine, as described in Paragraph 5.2.4. There is some evidence that catechol deaminated metabolites, such as 3,4-dihydroxy mandelic acid, are formed primarily by the action of MAO within adrenergic nerves. On the other hand, extraneuronal MAO oxidatively deaminates only compounds which have previously been O-methylated. 

Hippuric acids, which are formed as Phase 2 metabolic products from toluene, the xylenes, benzoic acid, ethylbenzene, and closely related compounds, can be determined as biological markers of exposure. The formation of hippuric acid from toluene is shown in Chapter 23, Figure 23.17. Structurally similar 4-methylhippuric acid is produced metabolically from /7-xylene by the same process that produces hippuric acid from toluene. Other metabolites that may be formed from aryl solvent precursors include mandelic acid and phenylgloxylic acid. 

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