Mandelate degradation

Huang, H.-R. and J.-H. Xu, Preparation of (S)-mandelic acid from racemate using growing cells of Pseudomonas putida ECU1009 with (R)-mandelate degradation activity. Biochem. Eng.., 2006. 30(1) 11-15. 

The mandelate pathway in Pseudomonas putida involves successive oxidation to benzoyl formate and benzoate, which is further metabolized via catechol and the 3-ketoadipate pathway (Figure 8.35a) (Hegeman 1966). Both enantiomers of mandelate were degraded through the activity of a mandelate racemase (Hegeman 1966), and the racemase (mdlA) is encoded in an operon that includes the next two enzymes in the pathway—5-mandel-ate dehydrogenase (mdlB) and benzoylformate decarboxylase (mdlC) (Tsou et al. 1990). 

FIGURE 8.35 Degradation of (a) mandelate, (b) 4-hydroxyacetophenone by side-chain oxidation pathways, (c) acetophenone by Baeyer-Villiger monooxygenation. 

Sze IS-Y, S Dagley (1987) Degradation of substituted mandelic acids by meta fission reactions. J Bacteriol 169 3833-3835. 

The degradation of mandelic acid by the bacterium Pseudomonas putida (Chapter 25) is initiated by mandalate racemase, another (a/(3)8-barrel protein.101 X-ray structures of bound inhibitors together with modeling suggest that the side chain of Lys 264 is the catalytic base that abstracts the a-H from S-mandelate (Fig. 13-5) and that the catalytic pair of His 297 and Asp 270 acts as proton donor, or, in the reverse direction, as catalytic... 

Another enzyme of the mandelate pathway of degradation of aromatic rings (Fig. 25-8) is the cis,cis-muconate lactonizing enzyme which catalyzes the reaction of Eq. 13-23. It has a three-dimensional struc-... 

Kalfon L, Youdim MB, Mandel SA. 2007. Green tea polyphenol (-)-epigallocatechin-3-gallate promotes the rapid protein kinase C- and proteasome-mediated degradation of Bad Implications for neuroprotection. J Neurochem 100 992-1002. 

The hemicellulose-degrading enzymes (Ultraflo L) and the cellulases (Celluclast 1.5L) were kindly donated by Novozymes A/S. Celluclast 1.5L had a filter paper activity of 80 filter paper units/mL, determined according to the procedure of Mandels (8-9). For the present study the most important side activities of Ultraflo L were endo-l,4-P-xylanase, P-xylo-sidase, and a-arabinofuranosidase (10). 

Copolymerization offers considerable potential of engineering the properties and degradation rate of PHB over a broad range. HB has been copolymerized with a number of related species, e.g., e-CL, LA, 4-hydroxybutyrate and hydrox-ypropionate. Furthermore, a number of PHB blends have been prepared. Miscibility of PHB with PCL, PLA, POE, poly(mandelic acid), and poly(sebacic anhydride) has been demonstrated. PHB-poly(sebacic anhydride) blends offered controlled release of bupivacaine at a rate dependent on the PHB content [141]. Blending of P(HB-co-HV) with natural polysaccharides was proposed as a way... 

Degradative oxidation of a-hydroxy carboxylic acids furnishes aldehydes or ketones. Glycolic acid, lactic acid, and mandelic acid are converted into formaldehyde, acetaldehyde, and benzaldehyde, respectively, in 50% yields on refluxing with A -bromosuccinimide in water [745]. Periodates, with phase-transfer reagents, convert a-hydroxyhexanoic acid and mandelic acid into valeraldehyde and benzaldehyde in respective yields of 90 and 88% (equation 478) [776, 778]. 

It has been suggested that active transport systems for benzoate (Thayer and Wheelis 1982) and for mandelate (Higgins and Mandelstam 1972) are involved. In Rhizobium leguminosarum, 4-hydroxybenzoate hydroxylase activity is required for the uptake of 4-hydroxybenzoate (Wong et al. 1994), while in P. putida a gene cluster pcaRKF is involved in the transport of 4-hydroxybenzoate into the cells, their chemotactic response to the substrate and its degradation by ring hydroxylation (Harwood et al. 1994 Nichols and Harwood 1997). The situation for phenylacetate transport into P. putida U is... 

Degradation of L-mandelate — L-Mandelate is degraded by successive stages to benzoate which is then metabolized by the pathways outlined above for 3,4-dihydroxybenzoate. Details of the degradation were elucidated by similar means except that the task was considerably simplified by the commercial availability of most of the intermediates (Hegeman 1966a,b). 

Since racemic monomer was used to prepare 1 and 3 it is quite possible that only one of the two enantiomeric forms can be attacked by the enzyme. Earlier we found that the poly(amide-urethane) derived from natural mandelic acid was degraded more readily by both enzymes and fungi than the corresponding nonsubstituted poly(amide-urethane) derived from glycolic acid (6J. ... 

Substituted mandelic acids are key compounds in the synthesis of vanillin from phenols. However, the KIE observed during the oxidative degradation of mandelic acid into benzaldehyde is extremely dependent on the experimental conditions. 

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. 

Norepinephrine (NE) is taken up into the nerve terminus of the adrenergic neuron by neuronal reuptake mechanisms ( pumps ). It is then degraded intracellularly, by monoamine oxidase (MAO) (primarily MAOa, a mitochondrial enzyme) to form dihydroxymandelic acid. This is further inactivated by the tissue enzyme catechol-O-methyl transferase (COMT). Transmitter remaining in the synaptic cleft is rapidly degraded, first by COMT, located on postsynaptic membranes, to form normetanephrine. This in turn is taken into the neuron and converted to 3-methoxy, 4-hydroxy mandelic acid (VMA) through the actions of MAO (see Figure, top of next page). 

Degradation studies demonstrated that (-)-norepinephrine is related to D-(-)-mandelic acid therefore, it was given the D-designation using the Fisher system. With the CIP system, norepinephrine is assigned the (R)-absolute configuration. 

Direct determination of cyclandelate by UV spectrophotometry is not practical since the oxidative degradation product, 3,3,5-trimethylcyclohexyl phenylglyoxalate has about 55 times the absorptivity (25). Spectrophotometric determinations of cyclandelate after hydrolysis to mandelic acid and oxidation to benzaldehyde have been reported (26,27). 

---