JP7234923B2 - 測定対象物質を補酵素として測定する物質測定方法 - Google Patents
測定対象物質を補酵素として測定する物質測定方法 Download PDFInfo
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- JP7234923B2 JP7234923B2 JP2019520301A JP2019520301A JP7234923B2 JP 7234923 B2 JP7234923 B2 JP 7234923B2 JP 2019520301 A JP2019520301 A JP 2019520301A JP 2019520301 A JP2019520301 A JP 2019520301A JP 7234923 B2 JP7234923 B2 JP 7234923B2
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- 239000000126 substance Substances 0.000 title claims description 80
- 239000005515 coenzyme Substances 0.000 title claims description 28
- 238000000691 measurement method Methods 0.000 title claims description 17
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims description 85
- 238000000034 method Methods 0.000 claims description 54
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 49
- 235000019157 thiamine Nutrition 0.000 claims description 39
- 239000011721 thiamine Substances 0.000 claims description 39
- 229960003495 thiamine Drugs 0.000 claims description 38
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- 108090000790 Enzymes Proteins 0.000 claims description 33
- 238000005259 measurement Methods 0.000 claims description 24
- 239000003153 chemical reaction reagent Substances 0.000 claims description 22
- 238000002835 absorbance Methods 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 239000000758 substrate Substances 0.000 claims description 13
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- 229910001425 magnesium ion Inorganic materials 0.000 claims description 2
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 claims 2
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- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 11
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- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
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- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
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- LIPOUNRJVLNBCD-UHFFFAOYSA-N acetyl dihydrogen phosphate Chemical compound CC(=O)OP(O)(O)=O LIPOUNRJVLNBCD-UHFFFAOYSA-N 0.000 description 3
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- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/82—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving vitamins or their receptors
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Description
[チアミン二リン酸溶液の調製]
コカルボキシラーゼ(チアミン二リン酸、和光純薬工業株式会社、製品番号:031-03833)を10mg秤量するとともに500mM-リン酸緩衝液(pH)を40mL分注して精製水で100mLに定容することで、100mg/L-チアミンピロリン酸のリン酸緩衝液(pH6.7)溶液を調製した。
ピルビン酸オキシダーゼ(旭化成ファーマ株式会社、製品番号:T-45)を10ユニット、ペルオキシダーゼ(東洋紡株式会社、製品番号:PEO-301)を60ユニット、ピルビン酸カリウムを189mg、塩化マグネシウムを40mg、Triton X-100を20mgそれぞれ秤量するとともに、500mM-リン酸緩衝液(pH6.7)を4mL分注して精製水で10mLに定容することで、DA-67発色チアミンピロリン酸検出試薬の第一試薬(R1)を調製した。
前述した100mg/L-チアミン二リン酸溶液を1mL,500mM-リン酸緩衝液(pH6.7)を400mL分注して精製水で1000mL(1L)に定容することで、検量線作成用の標準液(Tstd)を調製した。また、吸光度測定のブランク(空試験値、Blk)は、200mM-リン酸緩衝液(pH6.7)を用いた。
分光光度計として、株式会社日立ハイテクサイエンス社製、製品番号:U-3310を用い、ブランク(Blk)、標準液(Tstd)または検体(Tsam)と第一試薬(R1)と第二試薬(R2)とをそれぞれ1:6:2の比率で混合し(Blk/Tstd/Tsam:R1:R2=1:6:2)、波長700nm、温度37℃、タイムスキャン測定の測定条件で吸光度変化を測定した。
[NADH溶液の調製]
NADH(ナカライテスク株式会社製、製品番号:24335-61)は、Tris-HCl緩衝液として複数種類の濃度(31.25μM,62.5μM,125μM,250μM,500μM,1000μM)のものを調製した。また、吸光度測定のブランク用に、NADHを含有しないTris-HCl緩衝液のみ(NADHが0μM)を用いた。
10mMのTris-HCl緩衝液(pH9.5)に、ピルビン酸の濃度が2mMとなるように混合することで、第一試薬であるピルビン酸溶液を調製した。
20mMのTris-HCl緩衝液(pH7.0)に、乳酸デヒドロゲナーゼ(東洋紡株式会社製、製品名:LCD-209)の濃度が30ユニット/mLとなるように混合することで、第二試薬である乳酸デヒドロゲナーゼ溶液を調製した。
測定対象の試料(サンプル)であるNADH溶液25μLと第一試薬450μLとを混合して吸光度測定用のA液を調製し、37℃で5分間加温した後に、A液の吸光度を測定した。その後、A液に対してさらに第二試薬を150μL混合して吸光度測定用のB液を調製し、37℃で5分間加温した後に、B液の吸光度を測定した。A液の吸光度をAbs.Aとし、B液の吸光度をAbs.Bとしたときに、吸光度変化ΔAbs.は、Abs.AとAbs.Bとの差分となる(ΔAbs.=Abs.A-Abs.B)。
Claims (3)
- 試料に対して、当該試料に含まれる測定対象物質を補酵素とする酵素と当該酵素の基質とを少なくとも添加して、当該酵素が触媒する化学反応により生成した生成物を測定し、
当該生成物の測定量に基づいて、前記試料に含まれる測定対象物質を定量する物質測定方法であって、
前記試料に含まれる検体が全血であり、
前記測定対象物質がチアミンであり、
前記化学反応を触媒する酵素がピルビン酸オキシダーゼであり、前記生成物が過酸化水素であるとともに、
当該過酸化水素の測定は、当該過酸化水素とロイコ色素とをペルオキシダーゼの触媒作用により反応させ、これにより発色した当該ロイコ色素の呈色度を、吸光度変化を測定することにより行われることを特徴とする、
物質測定方法。 - 試料に対して、当該試料に含まれる測定対象物質を補酵素とする酵素と当該酵素の基質とを少なくとも添加して、当該酵素が触媒する化学反応により生成した生成物を測定し、
当該生成物の測定量に基づいて、前記試料に含まれる測定対象物質を定量する物質測定方法であって、
前記試料に含まれる検体が全血であり、
前記測定対象物質がチアミンであり、
前記化学反応を触媒する酵素がピルビン酸オキシダーゼであり、前記生成物が過酸化水素であるとともに、
当該過酸化水素の測定は、当該過酸化水素とアミノアンチピリンとトリンダー試薬とをペルオキシダーゼの触媒作用により反応させ、生成するキノン系色素による呈色度を、吸光度変化を測定することにより行われることを特徴とする、
物質測定方法。 - 前記試料には、前記酵素および前記基質に加えて、前記測定対象物質以外の補因子として、フラビンアデニンジヌクレオチドおよびマグネシウムイオンを添加することを特徴とする、
請求項1または2に記載の物質測定方法。
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