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PubMed1982

Inhibitory effects of aryl trans-4-(aminomethyl)cyclohexanecarboxylate and aryl trans-4-(guanidinomethyl)cyclohexanecarboxylate on serine proteases, and their antiallergic effects.

Since serine protease in involved in histamine release from mast cells, we attempted to prepare new protease inhibitors, trans-4-(guanidinomethyl)cyclohexanecarboxylic acid (GmcHX-CO2H) esters, and examined their inhibitory effects on typical serine proteases and on histamine release induced by compound 48/80. We compared their effects with those of trans-4-(aminomethyl)cyclohexanecarboxylic acid (AmcHx-CO2H) esters. AmcHxCO2H and GmcHxCO2H esters inhibited the esterolytic activity of trypsin, but GmcHx-CO2H esters had little or no inhibitory effect on caseinolytic activity whereas AmcHxCO2H esters strongly inhibited the latter. AmcHCO2H esters strongly inhibited plasmin but had no effect on chymotrypsin. GmcHxCO2H esters strongly inhibited the esterolytic activity of chymotrypsin, but had no effect on chymotrypsin-induced caseinolysis. Both GmcHxCO2H an AmcHxCO2H esters inhibited urokinase. Of the esters of AmcHxCO2H and GmcHxCO2H tested, only GmcHxCO2H p-tert-butylphenyl ester (GmcHxCOOPhBut) at low concentration (27 microM) strongly inhibited histamine release from rat mast cells induced by compound 48/80. GmcHxCOOPhBut was effective in preventing active systemic anaphylaxis and passively sensitized guinea pigs. Its effectiveness in preventing anaphylactic phenomena might be due to its strong inhibitory effects on histamine release from mast cells.

Acetylcholine↗

PubMed1989

1H NMR studies of aliphatic ligand binding to human plasminogen kringle 4.

A detailed 1H NMR analysis of ligand binding to the human plasminogen kringle 4 domain has been carried out at 300 MHz. The ligands that were investigated are N alpha-acetyl-L-lysine, L-lysine methyl ester, N alpha-acetyl-L-lysine methyl ester, L-lysine hydroxamic acid, trans-(aminomethyl)cyclohexanecarboxylic acid (AMCHA), and 4-(aminomethyl)bicyclo[2.2.2]octane-1-carboxylic acid (AMBOC). Specific ligand-binding effects were detected via two-dimensional COSY experiments. The side chains that are the most perturbed by ligand presence are those from Trp62, Phe64, and Trp72. Ligand-kringle saturation transfer (Overhauser) experiments show that the aromatic rings from these three residues, especially Trp72, are in direct contact with the ligand. These results add support to a previously reported model of the kringle 4 lysine-binding site [Ramesh, V., Petros, A. M., Llinás, M., Tulinsky, A., & Park, C. H. (1987) J. Mol. Biol. 198, 481-498] by which these aromatic groups are assigned a key role in establishing hydrophobic interactions with the ligand molecule. Equilibrium association constants (Ka) and kinetic rate constants (kon, koff) were determined for the binding of the various linear and cyclic ligands to kringle 4. We find that those ligands whose carboxylate function is blocked bind significantly weaker (Ka approximately less than 2 mM-1) than the corresponding analogues where the anionic center is present (Ka approximately greater than 20 mM-1), which underscores the relevance of the polar group in stabilizing the interaction with the kringle 4 binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

Histidine↗

PubMed1987

Tranexamic acid.

Explore the source record for details and available documents.

Cyclohexanecarboxylic Acids↗

PubMed1979

Gas-chromatographic analysis for valproic acid as phenacyl esters.

We describe a novel isothermal gas-chromatographic procedure for measuring valproic acid. Plasma, with cyclohexanecarboxylic acid added as internal standard, is selectively extracted with pentane to minimize the extraction of other acidic drugs. To convert carboxylic acids to their phenacyl esters, alpha-bromoacetophenone is added to the organic extract before evaporating the solvent. These esters are relatively less volatile than the acids themselves and the extracting solvent can be removed without any loss of valproic acid or internal standard. The phenacyl esters, when chromatographed on 3% OV-17, produce sharp, well-shaped peaks and show high response for the flame ionization detector. Valproic acid is well separated from the internal standard, from reagents and plasma constituents, and from some commonly prescribed drugs that we examined. When alpha-bromo-p-nitroacetophenone is sued as the derivatizing agent, the resulting nitrophenacyl esters can be analyzed with use of a nitrogen-specific detector.

Acetophenones↗

PubMed1997

Comparison of in vitro carnitine and glycine conjugation with branched-side chain and cyclic side chain carboxylic acids in rats.

The substrate specificity for carnitine conjugation was examined using rat hepatocytes and kidney slices and compared with glycine conjugation which is a competitive pathway through the CoA thioester. For both hepatocytes and kidney slices, the best substrate for the camitine conjugate was cyclopropanecarboxylic acid followed by cyclobuthanecarboxylic acid (CBCA) and cyclohexanecarboxylic acid (CHCA). For the glycine conjugate, the best substrate was benzoic acid, with conjugation also occurring with CHCA and CBCA. These results suggest that carnitine transferase shows substrate specificity for cyclic side chain carboxylic acids of lesser carbon number, while glycine transferase shows inverse specificity. To compare directly the amounts of carnitine and glycine conjugates in the liver and the kidney, we estimated the endogenous amounts of carnitine and glycine and then multiplied the results by the production ratio of each conjugate. With respect to the enzyme activity per unit tissue weight, the kidney tended to show higher activities for both conjugates than the hepatocytes. This is the first report, to our knowledge, of the kidney having high carnitine conjugation activity. Cyclopentanecarboxylic acid (CPECA) was the least effective substrate for glycine and carnitine conjugates in both hepatocytes and kidney slices, CPECA may not readily undergo esterification with CoA. The branched-side chain carboxylic acids, such as pivalic acid (PA) and isobutylic acid, were also poor substrates for carnitine and glycine conjugates in rat hepatocytes and kidney slices.

Animals↗

PubMed2005

A2A adenosine receptors on bone marrow-derived cells protect liver from ischemia-reperfusion injury.

Activation of the A2A adenosine receptor (A(2A)R) during reperfusion of various tissues has been found to markedly reduce ischemia-reperfusion injury. In this study, we used bone marrow transplantation (BMT) to create chimeric mice that either selectively lack or selectively express the A(2A)R on bone marrow-derived cells. Bolus i.p. injection of the selective A2A agonist, 4-[3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-piperidine-1-carboxylic acid methyl ester (ATL313; 3 microg/kg), at the time of reperfusion protects wild-type (wt) mice from liver ischemia-reperfusion injury. ATL313 also protects wt/wt (donor/recipient BMT mouse chimera) and wt/knockout chimera but produces modest protection of knockout/wt chimera as assessed by alanine aminotransferase activity, induction of cytokine transcripts (RANTES, IFN-gamma-inducible protein-10, IL-1alpha, IL-1-beta, IL-1Ralpha, IL-18, IL-6, and IFN-gamma), or histological criteria. ATL313, which is highly selective for the A(2A)R, produces more liver protection of chimeric BMT mice than 4-[3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-cyclohexanecarboxylic acid methyl ester, which is rapidly metabolized in mice to produce 4-[3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-cyclohexanecarboxylic acid, which has similar affinity for the A(2A)R and the proinflammatory A3 adenosine receptor. GFP chimera mice were created to show that vascular endothelial cells in the injured liver do not account for liver protection because they are not derived by transdifferentiation of bone marrow precursors. The data suggest that activation of the A(2A)R on bone marrow-derived cells is primarily responsible for protecting the liver from reperfusion injury.

Adenosine A2 Receptor Agonists↗

PubMed2003

Highly potent chiral labeling reagents for the discrimination of chiral alcohols.

Highly sensitive chiral labeling reagents, (1R,2R)- and (1S,2S)-2-(2,3-anthracenedicarboximido)cyclohexanecarboxylic acids [(1R,2R)- and (1S,2S)-A] and (1R,2R)- and (1S,2S)-2-(2,3-naphthalenedicarboximido)cyclohexanecarboxylic acids [(1R,2R)- and (1S,2S)-A'], were prepared. Reagent A has enabled us to discriminate the enantiomers of anteiso fatty alcohols up to C9 methyl branching by 1H NMR, and both reagents A and A' have allowed up to C16 methyl branching at the 10(-15) molar level by fluorescence detected reversed-phase HPLC.

Journal Article↗

PubMed2004

Degradation pathways of cyclic alkanes in Rhodococcus sp. NDKK48.

The degradation pathways for cyclic alkanes (c-alkanes) in Rhodococcus sp. NDKK48 were investigated. Strain NDKK48 used dodecylcyclohexane as a sole carbon and energy source, and five metabolites in the dodecylcyclohexane degradation pathway were detected by gas-chromatography/mass spectra. The metabolites were identified as cyclohexanecarboxylic acid, cyclohexylacetic acid, 1-cyclohexene-1-acetic acid, 4-dodecylcyclohexanol, and 4-dodecylcyclohexanone. The strain degrades dodecylcyclohexane via a ring oxidation pathway and an alkyl side chain oxidation pathway. Cyclohexanecarboxylic acid was further oxidized to muconic acid via 1-cyclohexene-1-carboxylic acid and benzoic acid, and the muconic acid was finally used by strain NDKK48 for growth. Methylcyclohexane and cyclohexane were co-oxidized with hexadecane by strain NDKK48. Methylcyclohexane was degraded via a ring oxidation pathway, and the degradation pathway contained part of the Baeyer-Villiger oxidation for ring cleavage. Cyclohexane was also degraded by the same pathway as methylcyclohexane. Thus, strain NDKK48 has two pathways for the complete degradation of c-alkanes.

Biodegradation, Environmental↗

PubMed1984

Induction of neutrophilic differentiation of human promyelocytic leukemic cells by branched-chain carboxylic acid anticonvulsant drugs.

The anticonvulsant drug 1-methyl-1-cyclohexanecarboxylic acid ( MCCA ) has been shown to cause maturation of murine neuroblastoma cells in vitro at concentrations that are pharmacologically achievable. HL-60 human promyelocytic leukemia cells cultured with this drug underwent a dose-dependent decrease in growth. Similarly, neutrophilic differentiation, based on morphologic criteria and the acquisition of the ability to reduce nitroblue tetrazolium and phagocytose yeast, was observed. Valproic acid, a clinically available anticonvulsant that is chemically related to MCCA , likewise inhibited growth and promoted maturation of HL-60 cells, although only at concentrations above the recommended therapeutic blood levels. MCCA was additive in its ability to induce differentiation of HL-60 with retinoic acid, another compound that induces differentiation at pharmacologic concentrations. MCCA , or similar branched-chain fatty acids, may be useful in the treatment of human leukemia, particularly in combination with other differentiation-inducing drugs.

Anticonvulsants↗

PubMed1998

Characterisation of the appearance of radioactive metabolites in monkey and human plasma from the 5-HT1A receptor radioligand, [carbonyl-11C]WAY-100635--explanation of high signal contrast in PET and an aid to biomathematical modelling.

N-(2-(4-(2-Methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl)++ +cyclohexanecarboxamide (WAY-100635), labelled in its amido carbonyl group with 11C (t1/2 = 20.4 min), is a promising radioligand for the study of brain 5-HT1A receptors with positron emission tomography (PET). Thus, in PET experiments in six cynomolgus monkeys and seven healthy male volunteers, [carbonyl-11C]WAY-100635 was taken up avidly by brain. Radioactivity was retained in regions rich in 5-HT1A receptors, such as occipital cortex, temporal cortex and raphe nuclei, but cleared rapidly from cerebellum, a region almost devoid of 5-HT1A receptors. [Carbonyl-11C]WAY-100635 provides about 3- and 10-fold higher signal contrast (receptor-specific to nonspecific binding) than [O-methyl-11C]WAY-100635 in receptor-rich areas of monkey and human brain, respectively. To elucidate the effect of label position on radioligand behaviour and to aid in the future biomathematical interpretation of the kinetics of regional cerebral radioactivity uptake in terms of receptor-binding parameters, HPLC was used to measure [carbonyl-11C]WAY-100635 and its radioactive metabolites in plasma at various times after intravenous injection. Radioactivity cleared rapidly from monkey and human plasma. Parent radioligand represented 19% of the radioactivity in monkey plasma at 47 min and 8% of the radioactivity in human plasma at 40 min. [Carbonyl-11C]desmethyl-WAY-100635 was below detectable limits in monkey plasma and at most a very minor radioactive metabolite in human plasma. [11C]Cyclohexanecarboxylic acid was identified as a significant radioactive metabolite. In human plasma this maximally represented 21% of the radioactivity at 10 min after radioligand injection. All other major radioactive metabolites in monkey and human plasma were even more polar. No-carrier-added [carbonyl-11C]cyclohexanecarboxylic acid was prepared in the laboratory and after intravenous administration into cynomolgus monkey was shown with PET to give only a low uptake of radioactivity into brain tissue. The acid rapidly gave rise to several radioactive metabolites of higher polarity in plasma. The observed lack of any significant metabolism of [carbonyl-11C]WAY-100635 to highly lipophilic or pharmacologically potent radioactive compounds is consistent with its high signal contrast in primate brain.

Animals↗

PubMed2004

Further studies on the biosynthesis of the manumycin-type antibiotic, asukamycin, and the chemical synthesis of protoasukamycin.

Asukamycin (2), a metabolite of Streptomyces nodosus ssp. asukaensis ATCC 29757 and a member of the manumycin family of antibiotics, is assembled from three components, an "upper" polyketide chain initiated by cyclohexanecarboxylic acid, a "lower" polyketide chain initiated by the novel starter unit, 3-amino-4-hydroxybenzoic acid (3,4-AHBA), and a cyclized 5-aminolevulinic acid moiety, 2-amino-3-hydroxycyclopent-2-enone (C(5)N unit). To shed light on the order in which these components are assembled, we synthesized in labeled form various potential intermediates and evaluated their incorporation into 2. The assembly of the molecular framework of 2 from 3,4-AHBA and cyclohexanecarboxylic acid apparently does not involve free, unactivated intermediates. However, protoasukamycin (12), the total synthesis of which is reported, was efficiently converted into 2, demonstrating that the modification of the aromatic ring to the epoxyquinol structure is the terminal step in the biosynthesis. The results suggest that the two polyketide chains are synthesized separately and that the "upper" chain must be connected to the "lower" polyketide chain before the C(5)N unit.

Anti-Bacterial Agents↗

PubMed1993

1,2-Cyclomethylenecarboxylic monoamide hydroxamic derivatives. A novel class of non-amino acid angiotensin converting enzyme inhibitors.

A series of monoamidic derivatives of cis- and trans-1,2-cyclohexanedicarboxylic and 1,2-cyclopentanedicarboxylic acids bearing either a carboxylic, sulfhydrylic, or hydroxamic group in the side chain were synthesized and evaluated in vitro for their inhibitory activity against angiotensin converting enzyme. The compounds were designed as potential ACE inhibitors of novel structure, assuming that a monoamidic residue of an 1,2-cyclomethylenedicarboxylic acid could be an alternative structure to the acylproline moiety, the carboxyl-terminal portion common to various ACE inhibitors. The most active compounds were found in the hydroxamic derivatives of cyclohexane series; within this series of derivatives a marked increase of potency was caused by alkylation of the amidic nitrogen with a methyl or ethyl group. Therefore enantiomers of the selected hydroxamic derivatives of cis- and trans-1,2-cyclohexanedicarboxylic acid were prepared by two different chiral synthetic routes and evaluated in vitro for their ACE inhibitor potencies. The active enantiomers both of the cis series (21a, 21c) and trans series (16b, 16d) were found to have all R configuration at the C-2 and R or S configuration at the C-1, while in the classical ACE inhibitors S configuration at the terminal carboxylate (corresponding to the C-1 of our compounds) is strictly required for activity. The most potent compound of the series was (1S,2R)-cis-2[[[2-(hydroxyamino)-2-oxoethyl]methylamino]carbonyl] cyclohexanecarboxylic acid (21a) with an IC50 value of 7.0 nM compared with the value of 3.0 nM for captopril. Further 21a was shown to be highly selective and competitive ACE inhibitor. These results indicate that this non-amino acid structure of inhibitors meets the ACE active site requirements for the binding. The binding compatibility of the most active compounds with a model of ACE active site was evaluated by molecular modeling techniques.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Expression, isolation and characterization of a mutated human plasminogen kringle 3 with a functional lysine binding site.

Each kringle of human plasminogen (HPg) except kringle 3 (K3) exhibits affinity for omega-aminocarboxylic acids. Assuming that the K3 domain contains a preformed but nonfunctional lysine binding site (LBS), Lys311 was altered by site-directed mutagenesis into Asp311 in accordance with the consensus sequence of the LBS. Cys297 involved in the interkringle disulfide bridge was mutated into Ser297 to minimize dimerization and aggregation. The mutated K3 TYQ[K3HPg/C297S/K311D]DS (r-K3mut) was expressed in Escherichia coli, isolated on an Ni2(+)-nitrilotriacetic acid-agarose column, refolded and purified on a lysine Bio-Gel column. Fluorescence titration indicates affinity of r-K3mut for omega-aminocarboxylic acids with the following association constants (Kass, mM-1): 5-aminopentanoic acid: 1.3; 6-aminohexanoic acid: 4.2; 7-aminoheptanoic acid: 0.5; trans-(aminomethyl)cyclohexanecarboxylic acid: 12.7; p-benzylaminesulfonic acid: 11.8. r-K3mut exhibits an affinity similar to native and mutated (R220G, E221D) K2. The results indicate the presence of a preformed but nonfunctional LBS in native K3 of HPg. We were able to demonstrate for the first time that an appropriate mutation in the LBS of a kringle produced a weak but distinct affinity for omega-aminocarboxylic acids.

Amino Acid Sequence↗

PubMed2000

N-acylated alpha-(3-pyridylmethyl)-beta-aminotetralin antagoinists of the human neuropeptide Y Y5 receptor.

Alpha-(3-Pyridylmethyl)-beta-aminotetralins were acylated with amino-piperidinyl and-pyrrolidinyl acetic acids, and with (aminomethyl)cyclohexanecarboxylic acid. Reaction with acyl chlorides, chloroformates, and isocyanates gave amides 8e, carbamates 9, and ureas 10, which bound to the Y5 receptor with nanomolar affinity. Congeners 11a and 11d containing a terminal benzimidazolone group were shown to be functional Y5 antagonists.

2-Naphthylamine↗

PubMed1995

Ligand binding to the tissue-type plasminogen activator kringle 2 domain: structural characterization by 1H-NMR.

Ligand binding to a recombinant human tissue-type plasminogen (tPA) kringle 2 domain has been characterized via 1H-NMR spectroscopy at 500 MHz. Seven omega-amino acid ligands were investigated: L-Lys, 6-aminohexanoic acid (6AHA), 7-aminoheptanoic acid (7AHA), trans-(aminomethyl)-cyclohexanecarboxylic acid (AMCHA), p-(aminomethyl)benzoic acid (PAMBA), p-(aminoethyl)benzoic acid (PAEBA), and p-benzylaminesulfonic acid (BASA). The interactions with two peptides containing a C-terminal lysyl residue, Tyr-Leu-Leu-Lys (YLLK) and Ala-Phe-Gln-Tyr-His-Ser-Lys (AFQYHSK), were also studied. The sequence AFQYHSK is found within the plasminogen N-terminal activation peptide while the tetrapeptide YLLK corresponds the 119-122 segment of the fibrinogen B beta-chain. Spectral comparison of ligand-free and ligand-containing kringle 2 samples leads to the conclusion that all the small ligands as well as the peptides' C-terminal lysyl residues interact with a common binding site in kringle 2. Two-dimensional spectra show that besides the Tyr36, Trp62, His64, Trp72, and Tyr74 aromatic rings, the Val35 and Asp55 aliphatic side chains also participate in ligand binding. Contact points with the ligands 6AHA and BASA were unambiguously identified from kringle 2-ligand nuclear Overhauser effects (NOEs). Overall, the ligand-induced chemical shifts and the intermolecular NOEs correlate remarkably well. Association constant (Ka) values for the kringle 2-ligand interactions were determined. Among the investigated ligands, BASA perturbs the kringle 2 spectrum the most and exhibits the highest affinity for kringle 2 (Ka approximately 233 mM-1). Of the two other aromatic ligands, PAEBA binds to kringle 2 less firmly (Ka = approximately 12 mM-1) than does the one-methylene group shorter analog PAMBA (Ka approximately 31 mM-1). By comparison, relative to 6AHA (Ka approximately 22 mM-1), the longer chain linear aliphatic ligand 7AHA interacts with kringle 2 with significantly higher affinity (Ka approximately 149 mM-1). By reference to the NMR-derived binding site structure, it is suggested that the higher affinity toward 7AHA may stem from (a) a relatively more favored ionic pairing between its carboxylate group and the LYs34 + Arg 69 side-chain cationic centers and (b) an enhanced interaction between the ligand hydrocarbon moiety and the kringle hydrophobic pocket, in particular with the Leu70 side chain. The latter is consistent with the relatively good affinity of kringle 2 for the cyclic hydrocarbon ligand AMCHA (Ka approximately 69 mM-1).(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1992

Purification and characterization of a novel enoyl coenzyme A reductase from Streptomyces collinus.

A novel NADPH-dependent enoyl reductase, catalyzing the conversion of 1-cyclohexenylcarbonyl coenzyme A (1-cyclohexenylcarbonyl-CoA) to cyclohexylcarbonyl-CoA, was purified to homogeneity from Streptomyces collinus. This enzyme, a dimer with subunits of identical M(r) (36,000), exhibits a Km of 1.5 +/- 0.3 microM for NADPH and 25 +/- 3 microM for 1-cyclohexenylcarbonyl-CoA. It has a pH optimum of 7.5, is most active at 30 degrees C, and is inhibited by both divalent cations and thiol reagents. Two internal peptide sequences were obtained. Ansatrienin A (an antibiotic produced by S. collinus) contains a cyclohexanecarboxylic acid moiety, and it is suggested that the 1-cyclohexenylcarbonyl-CoA reductase described herein catalyzes the final reductive step in the conversion of shikimic acid into this moiety.

Amino Acid Sequence↗

PubMed1988

Absorption of tranexamic acid as a prodrug in healthy volunteers.

The absorption of trans-4-(aminomethyl)cyclohexanecarboxylic acid (tranexamic acid, Cyklokapron) administered as the prodrug trans-4-(aminomethylcyclohexanecarboxylate hydrochloride (Kabi 2161) was investigated in 3 healthy volunteers. Kabi 2161 was given orally in doses of 1, 2, 3 and 3.5 mmol, respectively, and as a reference a clinical dose of 1.5 g tranexamic acid (9.6 mmol) was administered. At 3 mmol of Kabi 2161 the same maximum plasma concentration of tranexamic acid was obtained as with the reference drug but with Kabi 2161 it appeared earlier. The recovery of tranexamic acid in the urine 0-48 h after administration of Kabi 2161 was 84.7, 82.4, 89.4 and 97.5%, resp., of the increasing doses. For the tranexamic acid 37.0% could be recovered. A similar result was seen in the areas under the plasma concentration-time curves normalized for dose. With Kabi 2161, 13.1, 19.6, 14.4 and 14.3 mg.h/l.mmol were found compared to 8.0 mg.h/l.mmol with tranexamic acid. From these results it was concluded that Kabi 2161 markedly increased the bioavailability of tranexamic acid in man.

Adult↗

PubMed1993

Aromatization of 4-oxocyclohexanecarboxylic acid to 4-hydroxybenzoic acid by two distinctive desaturases from Corynebacterium cyclohexanicum. Properties of two desaturases.

We have previously demonstrated that Corynebacterium cyclohexanicum degrades cyclohexanecarboxylic acid, a bacteriocide, through a pathway including the aromatization of 4-oxocyclohexanecarboxylic acid to 4-hydroxybenzoic acid [Kaneda, T. (1974) Biochem. Biophys. Res. Commun. 58, 140-144]. Aromatization has now been shown to be catalysed by two desaturase enzymes. Under the action of desaturase I, 4-oxocyclohexanecarboxylic acid is converted to (+)-4-oxocyclohex-2-enecarboxylic acid which is then aromatized by desaturase II to 4-hydroxybenzoic acid. The latter reaction is presumed to occur via the unstable intermediate, 4-oxocyclohex-2,5-dienecarboxylic acid, which is spontaneously isomerized to 4-hydroxybenzoic acid. Desaturase I has been purified in an electrophoretically homogeneous form. It is monomeric with a molecular mass of 67 kDa and contains one tryptophan, one histidine and two cysteine residues per enzyme molecule. The enzyme produces an equivalent amount of 4-oxocyclohex-2-enecarboxylic acid and hydrogen peroxide from 4-oxocyclohexanecarboxylic acid. The properties of desaturase I have been studied in detail. Desaturase II is unstable and has been partially purified. Its characterization is therefore limited. However, the molecular mass of desaturase II was estimated to be 43 kDa by gel filtration chromatography. The characterization of both desaturase enzymes is described in this paper. The possible environmental importance of microbial aromatization in the biodegradation of compounds with the cyclohexane structure is discussed.

Amino Acids↗