Lipoxygenase properties

It is possible that dietary flavonoids participate in the regulation of cellular function independent of their antioxidant properties. Other non-antioxidant direct effects reported include inhibition of prooxidant enzymes (xanthine oxidase, NAD(P)H oxidase, lipoxygenases), induction of antioxidant enzymes (superoxide dismutase, gluthathione peroxidase, glutathione S-transferase), and inhibition of redox-sensitive transcription factors. 

Sekiya, J. Aoshima, H., Kajiwara, T., Togo, T. and Hatanaka, A. (1977). Purification and some properties of potato tuber lipoxygenase and detection of linoleic acid radical in the enzyme reaction. Agric. Biol. Chem. 41, 827-832. 

The kinetics of soybean lipoxygenase-1 in a biphasic medium is different from the kinetics in an aqueous system [Fig. 5(a),(b)]. The kinetic curve in the two-phase system has a sigmoid shape, which is due to surface active properties of LA and HP [25]. When initial LA concentration is small in the organic phase (0-5 mM) its transfer is poor and bioconversion in the aqueous phase is slow. 

Furthermore, in the system with coupled lipase and lipoxygenase, the production rate of HP is governed by the first enzymatic reaction and mass transfer. When TL,- is small (0 to 1 mM equiv. 3 mM LA), the kinetic curve has a sigmoid shape due to surface active properties of LA and HP [25]. Hydrolysis of TL and the increase of LA favor the transfer of LA. Such a transfer allows the lipoxygenase reaction to progress. Since lipox-ygenation consumes LA and produces HP, catalysis and transfer demonstrates a reciprocal influence. 

A significant advance in the understanding of the anti-inflammatory properties of Bupleurum fruticescens has been provided by Prieto et al. (36). The showed that a methanol extract from the aerial parts had a significant effect on 5-lipoxygenase activity, inhibiting both LTB4 and 5(S)-HETE production, with IC50 values of 112 and 95 (xg/mL, respectively. At concentrations of 200 (Xg/mL, the extract inhibited COX-1 (90%) and elastase activities (54%). What are the principles involved here, saponin ... 

Lopez-Nicolas JM, Perez-Gilabert M and Garcia-CarmonaF. 2001. Eggplant lipoxygenase (Solatium melon-gena) product characterization and effect of physicochemical properties of linoleic acid on the enzymatic activity. J Agric Food Chem 49(l) 433-438. 

Before taking leave of the eicosanoids, 1 need to point out that a second enzyme, 5-lipoxygenase, also metabolizes arachidonic acid. 5-Lipoxygenase initiates the synthesis of the leukotrienes from arachidonic acid. There is a whole family of leukotrienes and these molecules have a spectrum of biological properties. 1 will focus on one important leukotriene, LTB4. 

Certain echinacea constituents have demonstrated anti-inflammatory properties in vitro. Inhibition of cyclooxygenase, 5-lipoxygenase, and hyaluronidase may be involved. In animals, application of Epurpurea prior to application of a topical irritant reduced both paw and ear edema. Despite these laboratory findings, randomized, controlled clinical trials involving echinacea for wound healing have not been performed in humans. 

Misik, V., L. Bezakova, L. Malekova, and D. Kostalova. 1995. Lipoxygenase inhibition and antioxidant properties of protoberberine and aporphine alkaloids isolated from Mahonia aquifolium. Planta Med. 61 372-373. 

Muller, K. and K. Ziereis. 1994. The antipsoriatic Mahonia aquifolium and its active consitutents. I. Pro- and antioxidant properties and inhibition of 5-lipoxygenase. Planta Med. 60 421-424. 

A new class of compounds is reported to have dual inhibitory properties. They have a y-sultam skeleton and show potent inhibitory effects towards both COX-2 and 5-lipoxygenase as well as production of IL-1 in in vitro assays. These compounds have also proved to be effective in several animal arthritic models without any ulcerogenic activity. Among these compounds S-2474 ((E)-(5)-(3,5-di-fe/t.-butyl-4-hydroxy-benzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide) was selected as an anti-arthritic drug candidate and is now under clinical investigations (Inagaki et al., 2000). 

ML-3000 ((2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)-acetic acid) is a nonantioxidant dual inhibitor of both cyclooxygenase and 5-lipoxygenase. ML-3000 has been compared to indomethacin in a number of experimental models of inflammation. The analgesic effects of ML-3000 have also been assessed in a number of animal models. Phase II studies have shown a wide range of activities, including anti-inflammatory, analgesic, antiplatelet and antiasthmatic properties (Laufer et al., 1994 Chin and Wallace, 1999). 

Whatever the mechanism of action for the inhibition of 5-lipoxygenase by flavonoids, it appears to be distinct from the antioxidant properties of these compounds. The results comparing antioxidant activity with leukotriene inhibitory activity clearly demonstrate this distinction. The profound effects of metabolic transformation on the anti-inflammation activity of dietary flavonoids such as quercetin must also be considered in relation to in vitro studies, and further highlights the need to use actual metabolic forms of flavonoids rather than the free aglycone or glycosides occurring in the diet. 

Milk thistle may have anti-inflammatory properties. In vitro, silybin strongly and noncompetitively inhibits lipoxygenase and leukotriene formation. On the other hand, concentrations required to inhibit thromboxane and prostaglandin formation in vivo probably exceed dosing capabilities. Inhibition of leukocyte migration has also been observed in vivo and may be a factor when acute inflammation is present. 

Among hydrolases with allergenic properties used in the food industry there are a-amylases, amyloglucosidases, glucoamylases, cellulases, hemicellulases, pecti-nases, lipoxygenases, and xylanases (Bindslev-Jensen et al. 2006, Cullinan et al. 1997, Houba et al. 1997, Kanerva and Vanhanen 1999, 2001, Scheibe et al. 2001). Most of these enzymes are synthesized by A. otyzae fungi or Bacillus subtilis bacteria. 

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