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ユビセミキノンの機能(1)

2014-03-21 13:16:30 | ラジカル

705pxcomplex_i_svg(クリックで拡大)
図1 呼吸鎖複合体I内の電子伝達機構の模式図。図中Q はユビキノンを表す。

ユビキノン(UQ:図1)はミトコンドリア内膜や原核生物の細胞膜に存在する電子伝達体の1つで、呼吸鎖複合体I内の電子伝達の仲介を果たしている。ベンゾキノンの誘導体であり、比較的長いイソプレン側鎖を持つので、その疎水性のために膜中に保持される。酸化還元電位 (Eo') は+0.10V。ウシ心筋ミトコンドリア電子伝達系の構成成分として1957年に発見された。還元型のユビキノンは『ユビキノール』とも呼ばれる。また、補酵素Q、コエンザイムQ10、ビタミンQ、CoQ10、ユビデカレノン等と呼ぶこともある。

UQの酸化還元に関わるベンゾキノン誘導体部位はパラ型に酸素原子が結合しており、C2にはメチル基、C5,C6にはメトキシ基が結合している。C3にはイソプレン側鎖が結合しており、生体膜中に保持されるように長い炭素鎖を持つ。

Ubiquinone構造式

図1 ユビキノン(UQ)の構造。

イソプレン側鎖の数(n=)は高等動物では10、下等動物では6~9であり、イソプレン側鎖が長くなればなるほど黄橙色を呈するようになる。なおn=10のユビキノンは『UQ10』と略記される。ユビキノンは一電子還元を受けて中間型(ユビセミキノン)となる。中間型はプロトンキノンサイクル機構で機能している。ユビキノンの酸化還元様式を以下に示す。

Ubiquinoneredox.PNG

酸化型のユビキノンは275nmの波長の紫外光を吸収する。したがって、ユビキノンに電子伝達を行う酵素群の活性測定はこの波長に類する吸収帯を使用する。

ユビキノンはミトコンドリア内膜や原核生物の細胞膜から単離され、膜内の電子伝達に関与することが古くから知られており、特に、電子伝達系の呼吸鎖複合体I(NADH脱水素酵素)から呼吸鎖複合体III(シトクロムbc1複合体)への電子伝達に寄与している。

呼吸鎖複合体Iにおける反応

NADH + ユビキノン(UQox) → NAD+ + ユビキノール (UQred)

ユビキノンは日本では1970年代から医療用医薬品として軽度及び中等度のうっ血性心不全症状などに用いられてきた。また、複数の製薬メーカーが、一般用医薬品(OTC医薬品)・医薬部外品として、一般消費者向けの商品を発売している。安全性は比較的高く、米国ではコエンザイムQ10の名称でサプリメントとして広く用いられており、医師の処方箋なしに消費者が直接店頭などで購入できる。日本でも2001年に医薬品の範囲に関する基準(いわゆる「食薬区分」)が改正され、さらに2004年化粧品基準が改正されて、健康食品や化粧品への利用に道が開かれた。その結果、抗老化作用を訴求したユビキノン(コエンザイムQ10)含有の健康食品や化粧品がブームとなり、原材料の品薄で入手しにくいほどの人気を博していた時期があった。しかしながら、そのような薬効を臨床的に検討したデータはまだ乏しく、詳細な効果についてはまだ詳しくわかっていない。

2009年11月に、ユビキノンの抗酸化作用がマウスの老人性難聴の予防に効果があることを、東京大学が実験で明らかにした。それによると、人間にとっては1日20ミリグラムにあたる量のユビキノンを生後4ヶ月から与えられ続けてきたマウスは、人間の50歳に相当する生後15ヶ月の時点で、同じ月齢のマウスが45デシベル以上の音しか聞き取れないのに対し、12デシベルの小さい音を聞き取れるようになった。2013年7月16日に、小児性線維筋痛症発生の原因がユビキノンの欠乏にあることが、東京工科大学応用生物学部山本順寛教授らと、横浜市立大学医学部小児科との研究チームにより発見された。

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