3 ,4 -Dihydroxyphenylacetic acid

FIGURE 3-27 Three-dimensional chromatogram for oxidizable biological compounds at a multichannel amperometric detection system, consisting of an array of 16 carbon-paste electrodes held at different potentials. AA = ascorbic acid NE = norepinephrine DOPAC = 3,4-dihydroxyphenylacetic acid 5-HIAA = 5-hydroxyindole-3-acetic acid DA = dopamine HVA = homovanillic acid. (Reproduced with permission from reference 68.)... 

The problem of selectivity is the most serious drawback to in vivo electrochemical analysis. Many compounds of neurochemical interest oxidize at very similar potentials. While this problem can be overcome somewhat by use of differential waveforms (see Sect. 3.2), many important compounds cannot be resolvai voltammetrically. It is generally not possible to distinguish between dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) or l tween 5-hydroxytryptamine (5-HT) and 5-hydroxyindolacetic acid (5-HIAA). Of even more serious concern, ascorbic acid oxidizes at the same potential as dopamine and uric acid oxidizes at the same potential as 5-HT, both of these interferences are present in millimolar concentrations... 

Once returned to the presynaptic terminal, dopamine is repackaged into synaptic vesicles via the vesicular monoamine transporter (VMAT) or metabolized to dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO). Two alternative pathways are available for dopamine catabolism in the synapse, depending on whether the first step is catalyzed by MAO or catechol-O-methyltransferase (COMT). Thus, dopamine can be either deaminated to 3,4-dihydroxyphenylacetic acid (DOPAC) or methylated to 3-methoxytyramine (3-MT). In turn, deamination of 3-MT and methylation of DOPAC leads to homovanillic acid (HVA). In humans, cerebrospinal fluid levels of HVA have been used as a proxy for levels of dopaminergic activity within the brain (Stanley et al. 1985). 

The first CNT-modified electrode was reported by Britto et al. in 1996 to study the oxidation of dopamine [16]. The CNT-composite electrode was constructed with bro-moform as the binder. The cyclic voltammetry showed a high degree of reversibility in the redox reaction of dopamine (see Fig. 15.3). Valentini and Rubianes have reported another type of CNT paste electrode by mixing CNTs with mineral oil. This kind of electrode shows excellent electrocatalytic activity toward many materials such as dopamine, ascorbic acid, uric acid, 3,4-dihydroxyphenylacetic acid [39], hydrogen peroxide, and NADH [7], Wang and Musameh have fabricated the CNT/Teflon composite electrodes with attractive electrochemical performance, based on the dispersion of CNTs within a Teflon binder. It has been demonstrated that the electrocatalytic properties of CNTs are not impaired by their association with the Teflon binder [15]. 

J. Wang, M. Li, Z. Shi, N. Li, and Z. Gu, Electrocatalytic oxidation of 3,4-dihydroxyphenylacetic acid at a glassy carbon electrode modified with single-wall carbon nanotubes. Electrochim. Acta 47, 651-657 (2001). 

Furthermore, Laranjinha and Cadenas [58] have recently showed that nitric oxide oxidizes 3,4-dihydroxyphenylacetic acid (DOPAC) to form nitrosyl anion and the DOPAC semiqui-none supposedly by one-electron transfer mechanism. 

HIAA, 5-hydroxyindoleacetic acid CGRP, calcitonin-gene-related peptide DOPAC, 3,4-dihydroxyphenylacetic acid ... 

Cassel GE, Koch M, Tiger G. 1995. The effects of cyanide on the extracellular levels of dopamine, 3,4,-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxyindoleacetic acid and inositaol phospholipid breakdown in the brain. Neurotoxicology 16(l) 73-82. 

Also, harmala alkaloids create effects on monoamine turnover. Postnatal rats administered harmaline (shortly before birth) have elevations in brain levels of the norepinephrine metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG), but decreases in the dopamine and serotonin metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) (Okonmah et al. 

Boonen G, Ferger B, Kuschinsky K, Haberlein H. (1998). In vivo effects of the kavalactones (+)-dihydromethysticin and (H-/-)-kavain on dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid levels in striatal and cortical brain regions. Planta Med. 64(6) 507-10. Boonen G, Haberlein H. (1998). Influence of genuine kavalactone enantiomers on the GABA-A binding site. Planta Med. 64(6) 504-6. 

Glick SD, Dong N, Keller RW Jr, Carlson JN. 1994. Estimating extracellular concentrations of dopamine and 3,4-dihydroxyphenylacetic acid in nucleus accumbens and striatum using microdialysis relationships between in vitro and in vivo recoveries. J Neurochem 62(5) 2017-2021. 

Westerink BH, Tuinte MH. 1986. Chronic use of intracerebral dialysis for the in vivo measurement of 3,4-dihydroxyphe-nylethylamine and its metabolite 3,4-dihydroxyphenylacetic acid. J Neurochem 46(1) 181-185. 

Fio. 36. Vloi t Hoff plou of the retention bctors of aromatic acids in reversed-phase chromatography using octadecyl silica as the stationaiy phase and neat aqueous 30 taM NaHiPO buffer (pH 2.0) (open symbols), or the same buffer containing 696 (v/v) of aceloni ti (closed symbols) as the eluent. Column S imSpherisorbODS, 230 x 4.6 mm. Eluites 3.4xlihydroxymandelic acid (O. ) 4 hydroxymandelic acid ( , ) 4-hydroxyphenylacetic acid (7. ) 3,4-dihydroxyphenylacetic acid (A, A). Reprinted with permission from Me-lander tt at. U77). 

Other phenolic acids and derivatives 4- (Acetoxythyl) -1,2 -dihydroxybenzene Dopac (3,4-dihydroxyphenylacetic acid) 4-hydroxyphenylacetic acid COOH HO- HO Lignans (+)-l-Acetoxypino resinol (+)-Pinoresinol, / (+)-Hydroxypinoresinol "7 WR OCH3 HO OCH3... 

Faced with this conundrum, I am forced to place more reliance upon the microdialysis findings, in view of the possible contamination of the electrochemical DA signal by other chemical species that oxidize at the same voltage as DA (for example, 3,4-dihydroxyphenylacetic acid [DOPAC], ascorbic acid, uric acid) (see Gardner, Chen, and Paredes... 

Hydroquinones. - 3,4-Dihydroxyphenylacetic acid, a metabolite of the neurotransmitter dopamine, has been shown to undergo oxidation by "NO to a semiquinone, which was observed by EPR upon spin stabilisation with Mg2+ ions.119 Formation of the radical may be a crucial event in the development of Parkinson s disease (section 18.3). 4-Hydroxyestradiol, which has been implicated in breast cancer, is oxidised to a semiquinone by HRP. Mutagenicity is believed to result from addition of the quinone metabolite to DNA.120... 

Substrate specificity relative activity in parenthesis) 3.4- Dihydroxyphenylacetic acid (100) 3.4- Dehydroxyphenylpropionic acid (2.9) N-Formyl dopa (0.9) Dopa (0.3) Protocatechuic acid (0.13) Protocatechuic acid (100) 3,4-Dihydroxy-9,10-secoandrosta-1,3,5 (10)-triene-9,17-dione-3-lsopropylcatechol (100) 3-t-Butyl-5-methylcatechol (82.4) 3- Methylcatechol (7.4) 4- Methylcatechol (4.3) Catechol (0.6)... 

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