3.4- Dihydroxyphenylpropionic acid

Further transformation included additional hydroxylation steps leading to 2,6-dihydroxyquinoline and a trihydroxyquinoline (probably 2,5,6-trihydroxyquinoline). Shukla [322], working with Pseudomonas sp. identified an alternate pathway, involving additional metabolites, besides the 2-hydroxyquinoline and 8-hydroxycoumarin. These were 2,8-dihydroxyquinoline and 2,3-dihydroxyphenylpropionic acid. Quinoline-adapted cells were also able to transform 2-hydroxyquinoline and 8-hydroxycoumarin without a lag phase, providing additional support for their intermediate role as intermediates in the metabolism of quinoline. 

Quinaldine (2-methyl-quinoline) (2) 2-methyl-4(lH)-quinolinone (3) 3 -hydroxy-2-methyl-4( 1 H)quinolinone (4) N-acetylanthranilic acid (5) Anthranilic acid (6) Catechol (1) Quinoline (2) 2(lH)quinolinone (3) 8-hydroxy-2(lH)quinolinone (4) 8-hydroxycoumarin (5) 2, 3-dihydroxyphenylpropionic acid... 

One way to circumvent this problem would be to administer concomitantly an agent able to inhibit the AADC peripherally, but is a compound that will not penetrate the BBB itself. Several such inhibitors have been developed experimentally. The compound in clinical use, oc-methyl-(x-hydrazino-3,4-dihydroxyphenylpropionic acid (a-methyldopahy-drazine), is officially named carbidopa. Carbidopa is not generally available for clinical use alone but as a 1 10 and 1 4 combination product Levodopa-Carbidopa (Sinemet). This product alleviates some clinical difficulties associated with L-DOPA. Much lower doses of levodopa (by 75%) now achieve the desired results. 

Griffiths LA. 3,5-dihydroxyphenylpropionic acid, a further metabolite of sinapic acid. Experientia 1970 26 723-724. 

In principle, any simple monophenol and the corresponding diphenol could behave as a PPO substrate, taking into due account that diphenols are quinonized much faster than monophenols, owing to as well as differences. As a general rule, bulky and/or crowded substituents too close to the phenolic hydroxyl, prevent or at least render more difficult any enzyme/substrate interaction [84]. In the majority of cases chlorogenic acid, caffeic acid, catechin, 3,4-dihydroxyphenylpropionic... 

Infrared spectroscopy was one of the tools used (Levy and Frost, 1966) for a definitive identification of 2,3-dihydroxyphenylpropionic add, the product from the reaction between the enzyme, melilotate hydroxylase (from extracts of the Arthrobac-ter species), and melilotic acid, NADH, and oxygen. 

Fig. 16.14 Chromatogram of organic acids extracted using solvents from the urine of a patient with hereditary tyrosinaemia and separated as their methoxime and tri-methylsilyl derivatives on 3 per cent OV-17 using temperature programming from 80°C to 260°C at 4°C min Peak identifications are 1, urea plus phosphate 2, succinate 3, 2-methyl-3-hydroxybenzoate (internal standard) 4, 2-oxoglutarate 5, 4,6-dioxo-heptanoate (succinylacetone) 6, 4-hydroxyphenylacetate 7, aconitate 8, citrate 9, isocitrate 10, dihydroxyphenylpropionate 11, 4-hydroxyphenyl-lactate 12, 4-hydroxyphenylpyruvate 13, 3,5-dioxo-octanedioate (succinylacetoacetate). (Redrawn with modifications from Lindblad etal, 1977)...

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