Disease relevance of cinnamic acid

• Based upon these findings, preclinical and clinical trials of topical cinnamate esters as proteasome inhibitors are warranted for psoriasis and other inflammatory disorders [1].
• On the formation of 3-phenylpropionate and the different stereo-chemical course of the reduction of cinnamate by Clostridium sporogenes and Peptostreptococcus anaerobius [2].
• Anaerobic degradation of trans-cinnamate and omega-phenylalkane carboxylic acids by the photosynthetic bacterium Rhodopseudomonas palustris: evidence for a beta-oxidation mechanism [3].
• Methyl cinnamate derivatives enhance UV-induced mutagenesis due to the inhibition of DNA excision repair in Escherichia coli B/r [4].
• Degradation of cinnamate via beta-oxidation to benzoate by a defined, syntrophic consortium of anaerobic bacteria [5].

High impact information on cinnamic acid

• The structure of the free enzyme shows a significant proportion of the active sites in the crystal to contain a naturally occurring, noncovalently bound tetrapeptide inhibitor [Dixon, M.M. & Matthews, B.W. (1989) Biochemistry 28, 7033-7038], even after cinnamate acylation and photolysis [6].
• Visible light excitation of CdSe nanocrystals triggers the release of coumarin from cinnamate surface ligands [7].
• Initial orientation and distances of ring protons to the iron do not explain the selective hydroxylation of cinnamate in the 4-position or the formation of single products from the thienyl compounds [8].
• Paramagnetic relaxation effects of CYP73A1-Fe(III) on the 1H-NMR spectra of cinnamate and analogs indicate that their average initial orientation in the active site is parallel to the heme [8].
• X-ray diffraction studies of photoactivation using a flow cell show that the cinnamate B acyl enzyme complex is fully capable of light-induced isomerization and regeneration of native enzyme in the crystalline state [9].

Chemical compound and disease context of cinnamic acid

• Recombinant Escherichia coli cells containing four genes for a phenylalanine ammonia-lyase, cinnamate/coumarate:CoA ligase, chalcone synthase, and chalcone isomerase, in addition to the acetyl-CoA carboxylase, have been established for efficient production of (2S)-naringenin from tyrosine and (2S)-pinocembrin from phenylalanine [10].
• A gene (cinI) encoding a cinnamoyl ester hydrolase (CEH) has been isolated from the ruminal bacterium, Butyrivibrio fibrisolvens E14, using a model substrate, MUTMAC [4-methylumbelliferoyl (p-trimethylammonium cinnamate chloride)] [11].
• Phenylalanine ammonia lyase in the management of phenylketonuria: the relationship between ingested cinnamate and urinary hippurate in humans [12].

Biological context of cinnamic acid

• Substitution of a diethylamino group on the para position of the cinnamate ring causes a 1000-fold increase in the thermal stability of the inhibitor toward hydrolysis and deacylation [13].
• With the aid of partial amino acid sequences determined for cinnamate 4-hydroxylase (P450C4H) purified from mung bean seedlings, two cDNA clones were isolated and their inserts were completely sequenced [14].
• Mutagenic effects of racemic trans-epoxy cinnamate as well as the enantiomerically pure trans-epoxy cinnamates were observed in the Ames test with S. typhimurium strains TA1535, TA1537, TA1538 and TA100 without metabolic activation [15].
• The kinetics of cinnamate transport in the absence or presence of a surplus of either unlabelled cinnamate or unlabelled butyrate indicates a reduction in the apparent affinity of the Na(+)-dependent mechanism involved in cinnamate uptake [16].
• 4-Phenylbutyrate was a more effective inhibitor of histone deacetylase and inducer of histone acetylation than the structural analogs examined including 2- and 3-phenylbutyrate, cinnamate, methoxycinnamate, 2-phenoxybutyrate and phenoxyacetate [17].

Anatomical context of cinnamic acid

• A system that mimics the human gastrointestinal tract was combined with a computer simulation to evaluate the survival rate and cinnamate 4-hydroxylase activity of a recombinant model of Saccharomyces cerevisiae expressing the plant P450 73A1 [18].
• To assess the activity in vivo, the free or entrapped enzymes and then Phe were injected into rat duodenum, and cinnamate, a product, in plasma was determined as the most direct evidence of the enzyme activity [19].
• Microsomes from transformed yeast catalysed trans-cinnamate hydroxylation with high efficiency [20].
• Soleus muscle also recovered completely in the presence of cinnamate, whereas extensor digitorum longus hardly recovered at all [21].

Associations of cinnamic acid with other chemical compounds

• The unusual benzoate starter unit in soraphen A derives from phenylalanine via cinnamate in a beta-oxidative (plant-like) pathway; 3-phenyl-3-hydroxypropanoate incorporates directly into soraphen by loading onto module 2 of the PKS and indirectly from the beta-oxidative pathway to generate benzoyl CoA [22].
• In contrast, treatment of the cell cultures with a glucan elicitor from Phytophthora megasperma f. sp. glycinea did not induce flavonoid 3'-hydroxylase nor chalcone isomerase but caused a strong increase in the activities of phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, and NADPH--cytochrome reductase [23].
• The ability of Populus C4H isoforms to convert trans-cinnamate into p-coumaric acid was verified by the examination of yeast recombinant PtreC4H proteins [24].
• Studies of the methylated ethyl acetate extract of the trunk wood of MYRIANTHUS ARBOREUS (Cec-ropiaceae) have resulted in the isolation of five known pentacyclic triterpenes and a new lignan cinnamate [25].
• Strain JA2(T) grew on benzoate, 2-aminobenzoate (anthranilate), 4-aminobenzoate, 4-hydroxybenzoate, phthalate, phenylalanine, trans-cinnamate, benzamide, salicylate, cyclohexanone, cyclohexanol and cyclohexane-2-carboxylate as carbon sources and/or electron donors [26].

Gene context of cinnamic acid

• Six novel halogenated soraphen analogues have been isolated from the wild-type producing organism using precursor directed biosyntheses; the best 'delivery vehicle' for the novel starter acids was cinnamate but ortho substituents were not tolerated by the soraphen PKS [27].
• Molecular cloning and sequencing of a cDNA encoding mung bean cytochrome P450 (P450C4H) possessing cinnamate 4-hydroxylase activity [14].
• Using an EDC/NHS conjugation method, collagen was chemically modified to incorporate a photosensitive cinnamate moiety [28].
• Complex formation in aqueous solutions of trans-cinnamic acid or trans-cinnamate ion (the substrate, S) and alpha-cyclodextrin (the ligand, L) can be described quantiatively as the 1:1 and 1:2 complexes, SL and SL2 [29].
• Results indicate that the microsomal system constituted by the overexpressed yeast P450 reductase and CA4H is characterized by a 1:1 coupling between NADPH oxidation and cinnamate hydroxylation and by one of the highest turnover numbers reported for an NADPH-dependent P450 reaction [30].

Analytical, diagnostic and therapeutic context of cinnamic acid

• Significant immunosuppression also occurred at sites irradiated through the narrow-spectrum cinnamate-only sunscreen but was prevented by the two broad-spectrum sunscreens [31].
• From its inhibition of the fluorimetric titration of chymotrypsin with 4-methylumbelliferyl-p-trimethylammonium cinnamate it was shown to combine with chymotrypsin in a 1:1 molar ratio and thus to retain its biological activity [32].
• These data demonstrate that derivatization of collagen with photosensitive cinnamate moieties provides a facile route for solid-state crosslinking, thereby improving the mechanical properties of collagen and enhancing the potential applicability of collagen-based materials in tissue engineering and drug delivery [28].
• Importance of using solid lipid microspheres as carriers for UV filters on the example octyl methoxy cinnamate [33].
• A cDNA clone was generated from the elicited transcripts and assigned to cinnamate 4-monooxygenase based on sequence alignments and functional expression in yeast cells [34].

References