5‐Hydroxydecanoate (5‐HD) inhibits ischaemic and pharmacological preconditioning of the heart. Since 5‐HD is thought to inhibit specifically the putative mitochondrial ATP‐sensitive K+ (KATP) channel, this channel has been inferred to be a mediator of preconditioning. However, it has recently been shown that 5‐HD is a substrate for acyl‐CoA synthetase, the mitochondrial enzyme which ‘activates’ fatty acids. Here, we tested whether activated 5‐HD, 5‐hydroxydecanoyl‐CoA (5‐HD‐CoA), is a substrate for medium‐chain acyl‐CoA dehydrogenase (MCAD), the committed step of the mitochondrial β‐oxidation pathway. Using a molecular model, we predicted that the hydroxyl group on the acyl tail of 5‐HD‐CoA would not sterically hinder the active site of MCAD. Indeed, we found that 5‐HD‐CoA was a substrate for purified human liver MCAD with a Km of 12.8 ± 0.6 μm and a kcat of 14.1 s−1. For comparison, with decanoyl‐CoA (Km∼3 μm) as substrate, kcat was 6.4 s−1. 5‐HD‐CoA was also a substrate for purified pig kidney MCAD. We next tested whether the reaction product, 5‐hydroxydecenoyl‐CoA (5‐HD‐enoyl‐CoA), was a substrate for enoyl‐CoA hydratase, the second enzyme of the β‐oxidation pathway. Similar to decenoyl‐CoA, purified 5‐HD‐enoyl‐CoA was also a substrate for the hydratase reaction. In conclusion, we have shown that 5‐HD is metabolised at least as far as the third enzyme of the β‐oxidation pathway. Our results open the possibility that β‐oxidation of 5‐HD or metabolic intermediates of 5‐HD may be responsible for the inhibitory effects of 5‐HD on preconditioning of the heart.
Oxetane is a potential intermediate that is enzymatically formed during the repair of (6-4) DNA lesions by special repair enzymes (6-4 DNA photolyases). These enzymes use a reduced and deprotonated flavin to cleave the oxetane by single electron donation. Herein we report synthesis of DNA hairpin model compounds containing a flavin as the hairpin head and two different oxetanes in the stem structure of the hairpin. The data show that the electron moves through the duplex even over distances of 17 A. Attempts to trap the moving electron with N2O showed no reduction of the cleavage efficiency showing that the electron moves through the duplex and not through solution. The electron transfer is sequence dependent. The efficiency is reduced by a factor of 2 in GC rich DNA hairpins.
The tricyclic title compound, C11H15NO4, is an intermediate in the synthesis of (1S,2R,4R)‐4‐amino‐2‐(hydroxymethyl)cyclopentanol, which is an important carbocyclic analogue of β‐2‐deoxyribosylamine. All bond lengths and angles in the `exo epoxide' are in normal ranges.
Key indicatorsSingle-crystal X-ray study T = 193 K Mean '(C±C) = 0.003 A Ê R factor = 0.032 wR factor = 0.087 Data-to-parameter ratio = 9.1 For details of how these key indicators were automatically derived from the article, see
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