Disease relevance of MUCONIC ACID

• Both cycloisomerases convert cis,cis-muconate to (4S)-muconolactone by a syn lactonization, the absolute stereochemical outcome of which is identical to that observed with MLE from Pseudomonas putida [1].
• We have used an in vitro transcription system to study the roles of CatR, cis,cis-muconate, Escherichia coli RNA polymerase, and promoter sequences in expression of the cat and phe operons [2].
• mucK, a gene in Acinetobacter calcoaceticus ADP1 (BD413), encodes the ability to grow on exogenous cis,cis-muconate as the sole carbon source [3].
• Stereo- and regiospecific cis,cis-muconate cycloisomerization by Rhodococcus rhodochrous N75 [4].
• Of the three enzymes, TfdD of Ralstonia eutropha JMP134 (pJP4) was most specific, since its specificity constant for 2,4-dichloro-cis,cis-muconate was the highest, while the constants for cis,cis-muconate, 2-chloro- and 2,5-dichloro-cis,cis-muconate were especially poor [5].

High impact information on MUCONIC ACID

• Here, in vitro transcription assays demonstrated that two metabolites of aromatic compound catabolism, benzoate and cis,cis-muconate, act synergistically to activate gene expression [6].
• The binding affinity of CatR for its binding site in the catBC promoter region was shown to increase about 2.2-fold in the presence of the inducer, cis,cis-muconate [7].
• The catBC operon encodes two enzymes of the beta-ketoadipate pathway and also requires CatR and cis,cis-muconate for its expression [8].
• Transgenic plants also exhibit strikingly higher capabilities of removing catechol from their media and high efficiencies of converting catechol to cis,cis-muconic acid [9].
• An enzyme from the beta-ketoadipate pathway, MLE catalyses the conversion of cis,cis-muconate to muconolactone [10].

Chemical compound and disease context of MUCONIC ACID

• Roles of CatR and cis,cis-muconate in activation of the catBC operon, which is involved in benzoate degradation in Pseudomonas putida [11].
• Quantitative RT-PCR analysis revealed that pcaD mRNA levels increased sharply in response to protocatechuate, and a biotransformation experiment with cis,cis-muconate using Escherichia coli carrying both catBC and pcaD indicated that PcaD exhibited beta-ketoadipate enol-lactone hydrolase activity [12].

Biological context of MUCONIC ACID

• With the R39Q mutant, cis, cis-muconate showed negative cooperativity in active site binding with two K(d) values, 3.5 and 29 mM [13].
• Steady-state kinetic analysis of the divalent metal ion requiring cis,cis-muconate cycloisomerase catalyzed interconversion of cis,cis-muconate and (+)-muconolactone obeys Michaelis-Menten kinetics and the Haldane relationship from pH 6.2 to 8 [14].
• Enhanced induction of these isoenzymes is correlated with increased metabolic activation of BZ to excrete increased amounts of trans,trans muconic acid, the putative active metabolite of BZ, in urine [15].
• Benzoate decreases the binding of cis,cis-muconate to the BenM regulator despite the synergistic effect of both compounds on transcriptional activation [16].
• Moreover, in these mutants cyclization of 3-carboxymuconic acid seems to occur by a syn absolute stereochemical course, which is normally only observed for cis, cis-muconate lactonization in pseudomonads [17].

Anatomical context of MUCONIC ACID

• Blood lead of the nonatopic women (mean 55 microg/l) was positively correlated with CD4+-CD45RO-, CD3+-CD8+ and CD3--HLA-DR+ lymphocyte subsets, while urinary trans-trans muconic acid (a metabolite of benzene) of both groups of women (mean about 50 microg/l) was significantly correlated with NK CD16+CD56+ lymphocytes [18].
• Blood lead and urinary trans-trans muconic acid were barely correlated with immune parameters: the urinary metabolite of benzene of the control group was only correlated with CD16+-CD56+ cells indicating a slight effect of traffic on the immune system [19].
• Atmospheric benzene, urinary muconic acid (tt-MA) and leukocyte alkaline phosphatase activity (LAPA) were evaluated among 66 car mechanics, 34 road tanker drivers, and 28 nonexposed workers [20].
• The major metabolites found in plasma, liver, and bone marrow samples were muconic acid and hydroquinone [21].

Associations of MUCONIC ACID with other chemical compounds

• The inducible enzyme catalysing the conversion of cis,cis-muconate to (+)-muconolactone was purified 300-fold from the yeast Trichosporon cutaneum, grown on phenol [22].
• The binding of cis,cis-muconate to wild-type 4-OT upshifts Arg-11 Nepsilon (by 0.05 ppm) and downshifts Arg-39 Nepsilon (by 1.19 ppm), indicating differing electronic delocalizations in the guanidinium groups [13].
• Expression of the cat and clc operons requires the LysR-type transcriptional activators CatR and ClcR, and the inducer molecules cis,cis-muconate and 2-chloro-cis,cis-muconate [23].
• However, production of CatA1 during growth on 2CB or CCM was observed when cat2 genes were disrupted [24].
• Unlike both rats and mice, hydroquinone glucuronide (24-29%) and muconic acid (19-31%) were the primary urinary metabolites formed by hamsters [25].

Gene context of MUCONIC ACID

• Unusual regulatory features of this system include the abilities of both BenM and CatM to recognize the same inducer, cis,cis-muconate, and to regulate some of the same genes, such as catA and catB [26].
• The chromosomal benK gene was identified within a supraoperonic gene cluster involved in benzoate degradation by Acinetobacter sp. strain ADP1, and benK was expressed in response to a benzoate metabolite, cis,cis-muconate [27].
• All of the catB mutations increased cis,cis-muconate-activated ben gene expression in strains lacking BenM [28].
• Cloning and complete nucleotide sequence determination of the catB gene encoding cis,cis-muconate lactonizing enzyme [29].
• The catB and catC genes encode cis,cis-muconate lactonizing enzyme I (EC 5.5.1.1) and muconolactone isomerase (EC 5.3.3.4), respectively [30].

Analytical, diagnostic and therapeutic context of MUCONIC ACID

• The dissociation constant of the substrate analog cis,cis-muconate decreased 1.7-fold in the P1G mutant as determined by NMR titration [31].
• Phenylsulfate, muconic acid, and pre-phenylmercapturic acids as well as an unknown with a HPLC retention time of 7 min were the major metabolites in the liver [32].
• Capillary electrophoresis determination of urinary muconic acid as a biological marker for benzene in cigarette smoke [33].
• A gas chromatography/mass spectroscopy (GC/MS) assay was developed to measure urinary muconic acid, and the analyte in urine samples from workers occupationally exposed to benzene was determined [34].
• In a gel mobility shift assay using CatR1 and the DNA fragment containing the catB1 promoter region, the formation of two complexes, complex 1-1 (C1-1) and complex 1-2 (C1-2), was observed in the presence of cis,cis-muconate [35].

References