DOI: 10.1002/poc.1633. Enzymatic tunneling and kinetic isotope effects: chemistry at the crossroads

Enzymatic tunneling and kinetic isotope effects: chemistry at the crossroads

10.1002/poc.1633

Crossref journal-article

Wiley

Journal of Physical Organic Chemistry (311)

Abstract

AbstractKinetic isotope effects (KIEs), originally a tool for the physical organic chemist and mechanistic enzymologist, have been instrumental in furthering our understanding of quantum‐mechanical hydrogen tunneling in enzymatic systems. This review focuses on the use of KIE studies to investigate this phenomenon in enzyme‐catalyzed reactions. A number of enzymes wherein KIEs have been used as a probe for H‐tunneling are discussed, including dihydrofolate reductase (DHFR), alcohol dehydrogenase (ADH), and formate dehydrogenase (FDH). Particular emphasis has been placed on the significance of KIE results in exposing the chemical H‐transfer step in the complex kinetic cascades typical to these systems, as well as on questions regarding the influence of protein dynamics on tunneling and, consequently, on the whole enzymatic reaction. Copyright © 2009 John Wiley & Sons, Ltd.

Bibliography

Sen, A., & Kohen, A. (2010). Enzymatic tunneling and kinetic isotope effects: chemistry at the crossroads. Journal of Physical Organic Chemistry, 23(7), 613â619. Portico.

Authors 2

Arundhuti Sen (first)
Amnon Kohen (additional)

References 57 Referenced 45

10.1016/0304-4173(85)90014-X
10.1016/S0006-3495(66)86698-5
{'key': 'e_1_2_5_4_2', 'volume-title': 'Isotope Effects in Chemistry and Biology', 'author': 'Kohen A.', 'year': '2006'} / Isotope Effects in Chemistry and Biology by Kohen A. (2006)
10.1021/cr050301x
10.1146/annurev.biochem.75.103004.142800
10.1021/ci700167n
10.1021/cr050312q
10.1021/cr0503052
10.1038/nature06522
10.1021/ar700132n
10.1021/cr60211a004
{'key': 'e_1_2_5_13_2', 'volume-title': 'Reaction Rates of Isotopic Molecules', 'author': 'Melander L.', 'year': '1980'} / Reaction Rates of Isotopic Molecules by Melander L. (1980)
{'key': 'e_1_2_5_14_2', 'first-page': '1', 'volume-title': 'Quantum Tuneling in Enzyme‐Catalyzed Reactions', 'author': 'Carpenter B. A.', 'year': '2008'} / Quantum Tuneling in Enzyme‐Catalyzed Reactions by Carpenter B. A. (2008)
{'key': 'e_1_2_5_15_2', 'first-page': '3', 'volume-title': 'Enzyme Mechanism from Isotope Effects', 'author': 'Suhnel J.', 'year': '1991'} / Enzyme Mechanism from Isotope Effects by Suhnel J. (1991)
{'key': 'e_1_2_5_16_2', 'first-page': '549', 'volume-title': 'Isotope Effects in Chemistry and Biology', 'author': 'Kiefer P. M.', 'year': '2006'} / Isotope Effects in Chemistry and Biology by Kiefer P. M. (2006)
10.1146/annurev.bi.50.070181.000535
10.4324/9780203833575
10.1021/ja00364a026
10.1021/bi00318a016
10.1021/ja00532a035
10.1021/ja016909e
10.1021/ja054170t
10.1021/bi00263a040
10.1021/ja01554a077
10.1021/bi00683a013
{'key': 'e_1_2_5_27_2', 'first-page': '915', 'volume-title': 'Isotope Effects in Chemistry and Biology', 'author': 'Cleland W. W.', 'year': '2006'} / Isotope Effects in Chemistry and Biology by Cleland W. W. (2006)
{'key': 'e_1_2_5_28_2', 'first-page': '269', 'volume-title': 'Enzyme Mechanism from Isotope Effects', 'author': 'Parkin D. W.', 'year': '1991'} / Enzyme Mechanism from Isotope Effects by Parkin D. W. (1991)
10.1021/bi00556a020
10.1039/dc9827400229
10.1021/ja00319a060
10.1046/j.1432-1033.2002.03020.x
10.1021/ar6000507
10.1021/ja00081a061
10.1021/ja961827p
10.1021/bi00043a013
10.1021/ja012205t
10.1021/ja806354w
10.1126/science.2646716
10.1002/poc.610040607
10.1021/ja00287a029
10.1021/bi00510a016
10.1021/ja00355a038
{'key': 'e_1_2_5_44_2', 'first-page': '132', 'volume-title': 'Quantum Tunnelling in Enzyme‐Catalysed Reactions', 'author': 'Klinman J. P.', 'year': '2008'} / Quantum Tunnelling in Enzyme‐Catalysed Reactions by Klinman J. P. (2008)
10.1073/pnas.94.24.12797
10.1021/bi00072a003
10.1021/bi973184b
10.1038/20981
10.1021/ja002229k
10.1021/bi049004x
10.1098/rstb.2006.1873
10.1063/1.2372496
10.1073/pnas.0606976103
10.1002/pro.5560050626
10.1126/science.1159052
10.1021/ja031683w
10.1098/rstb.2006.1871
10.1021/bi0518242

Dates

Type	When
Created	15 years, 9 months ago (Nov. 25, 2009, 10:22 a.m.)
Deposited	1 year, 11 months ago (Sept. 14, 2023, 3:59 a.m.)
Indexed	1 month, 1 week ago (July 24, 2025, 7:30 a.m.)
Issued	15 years, 2 months ago (June 22, 2010)
Published	15 years, 2 months ago (June 22, 2010)
Published Online	15 years, 2 months ago (June 22, 2010)
Published Print	15 years, 2 months ago (July 1, 2010)

Funders 0

None

BibTeX

@article{Sen_2010, title={Enzymatic tunneling and kinetic isotope effects: chemistry at the crossroads}, volume={23}, ISSN={1099-1395}, url={http://dx.doi.org/10.1002/poc.1633}, DOI={10.1002/poc.1633}, number={7}, journal={Journal of Physical Organic Chemistry}, publisher={Wiley}, author={Sen, Arundhuti and Kohen, Amnon}, year={2010}, month=jun, pages={613–619} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        24
      ]
    ],
    "date-time": "2025-07-24T11:30:41Z",
    "timestamp": 1753356641940
  },
  "reference-count": 57,
  "publisher": "Wiley",
  "issue": "7",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2009,
            11,
            25
          ]
        ],
        "date-time": "2009-11-25T00:00:00Z",
        "timestamp": 1259107200000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2010,
        7
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title><jats:p>Kinetic isotope effects (KIEs), originally a tool for the physical organic chemist and mechanistic enzymologist, have been instrumental in furthering our understanding of quantum\u2010mechanical hydrogen tunneling in enzymatic systems. This review focuses on the use of KIE studies to investigate this phenomenon in enzyme\u2010catalyzed reactions. A number of enzymes wherein KIEs have been used as a probe for H\u2010tunneling are discussed, including dihydrofolate reductase (DHFR), alcohol dehydrogenase (ADH), and formate dehydrogenase (FDH). Particular emphasis has been placed on the significance of KIE results in exposing the chemical H\u2010transfer step in the complex kinetic cascades typical to these systems, as well as on questions regarding the influence of protein dynamics on tunneling and, consequently, on the whole enzymatic reaction. Copyright \u00a9 2009 John Wiley &amp; Sons, Ltd.</jats:p>",
  "DOI": "10.1002/poc.1633",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2009,
        11,
        25
      ]
    ],
    "date-time": "2009-11-25T15:22:44Z",
    "timestamp": 1259162564000
  },
  "page": "613-619",
  "source": "Crossref",
  "is-referenced-by-count": 45,
  "title": "Enzymatic tunneling and kinetic isotope effects: chemistry at the crossroads",
  "prefix": "10.1002",
  "volume": "23",
  "author": [
    {
      "given": "Arundhuti",
      "family": "Sen",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Amnon",
      "family": "Kohen",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2010,
        6,
        22
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_5_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0304-4173(85)90014-X"
    },
    {
      "key": "e_1_2_5_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0006-3495(66)86698-5"
    },
    {
      "key": "e_1_2_5_4_2",
      "volume-title": "Isotope Effects in Chemistry and Biology",
      "author": "Kohen A.",
      "year": "2006"
    },
    {
      "key": "e_1_2_5_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/cr050301x"
    },
    {
      "key": "e_1_2_5_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.biochem.75.103004.142800"
    },
    {
      "key": "e_1_2_5_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ci700167n"
    },
    {
      "key": "e_1_2_5_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/cr050312q"
    },
    {
      "key": "e_1_2_5_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/cr0503052"
    },
    {
      "key": "e_1_2_5_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature06522"
    },
    {
      "key": "e_1_2_5_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ar700132n"
    },
    {
      "key": "e_1_2_5_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/cr60211a004"
    },
    {
      "key": "e_1_2_5_13_2",
      "volume-title": "Reaction Rates of Isotopic Molecules",
      "author": "Melander L.",
      "year": "1980"
    },
    {
      "key": "e_1_2_5_14_2",
      "first-page": "1",
      "volume-title": "Quantum Tuneling in Enzyme\u2010Catalyzed Reactions",
      "author": "Carpenter B. A.",
      "year": "2008"
    },
    {
      "key": "e_1_2_5_15_2",
      "first-page": "3",
      "volume-title": "Enzyme Mechanism from Isotope Effects",
      "author": "Suhnel J.",
      "year": "1991"
    },
    {
      "key": "e_1_2_5_16_2",
      "first-page": "549",
      "volume-title": "Isotope Effects in Chemistry and Biology",
      "author": "Kiefer P. M.",
      "year": "2006"
    },
    {
      "key": "e_1_2_5_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.bi.50.070181.000535"
    },
    {
      "key": "e_1_2_5_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.4324/9780203833575"
    },
    {
      "key": "e_1_2_5_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00364a026"
    },
    {
      "key": "e_1_2_5_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00318a016"
    },
    {
      "key": "e_1_2_5_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00532a035"
    },
    {
      "key": "e_1_2_5_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja016909e"
    },
    {
      "key": "e_1_2_5_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja054170t"
    },
    {
      "key": "e_1_2_5_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00263a040"
    },
    {
      "key": "e_1_2_5_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja01554a077"
    },
    {
      "key": "e_1_2_5_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00683a013"
    },
    {
      "key": "e_1_2_5_27_2",
      "first-page": "915",
      "volume-title": "Isotope Effects in Chemistry and Biology",
      "author": "Cleland W. W.",
      "year": "2006"
    },
    {
      "key": "e_1_2_5_28_2",
      "first-page": "269",
      "volume-title": "Enzyme Mechanism from Isotope Effects",
      "author": "Parkin D. W.",
      "year": "1991"
    },
    {
      "key": "e_1_2_5_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00556a020"
    },
    {
      "key": "e_1_2_5_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1039/dc9827400229"
    },
    {
      "key": "e_1_2_5_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00319a060"
    },
    {
      "key": "e_1_2_5_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1432-1033.2002.03020.x"
    },
    {
      "key": "e_1_2_5_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ar6000507"
    },
    {
      "key": "e_1_2_5_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00081a061"
    },
    {
      "key": "e_1_2_5_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja961827p"
    },
    {
      "key": "e_1_2_5_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00043a013"
    },
    {
      "key": "e_1_2_5_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja012205t"
    },
    {
      "key": "e_1_2_5_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja806354w"
    },
    {
      "key": "e_1_2_5_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2646716"
    },
    {
      "key": "e_1_2_5_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/poc.610040607"
    },
    {
      "key": "e_1_2_5_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00287a029"
    },
    {
      "key": "e_1_2_5_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00510a016"
    },
    {
      "key": "e_1_2_5_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00355a038"
    },
    {
      "key": "e_1_2_5_44_2",
      "first-page": "132",
      "volume-title": "Quantum Tunnelling in Enzyme\u2010Catalysed Reactions",
      "author": "Klinman J. P.",
      "year": "2008"
    },
    {
      "key": "e_1_2_5_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.24.12797"
    },
    {
      "key": "e_1_2_5_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00072a003"
    },
    {
      "key": "e_1_2_5_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi973184b"
    },
    {
      "key": "e_1_2_5_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/20981"
    },
    {
      "key": "e_1_2_5_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja002229k"
    },
    {
      "key": "e_1_2_5_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi049004x"
    },
    {
      "key": "e_1_2_5_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1098/rstb.2006.1873"
    },
    {
      "key": "e_1_2_5_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1063/1.2372496"
    },
    {
      "key": "e_1_2_5_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0606976103"
    },
    {
      "key": "e_1_2_5_54_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/pro.5560050626"
    },
    {
      "key": "e_1_2_5_55_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1159052"
    },
    {
      "key": "e_1_2_5_56_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja031683w"
    },
    {
      "key": "e_1_2_5_57_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1098/rstb.2006.1871"
    },
    {
      "key": "e_1_2_5_58_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi0518242"
    }
  ],
  "container-title": "Journal of Physical Organic Chemistry",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fpoc.1633",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fpoc.1633",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1002/poc.1633",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        9,
        14
      ]
    ],
    "date-time": "2023-09-14T07:59:32Z",
    "timestamp": 1694678372000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1002/poc.1633"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2010,
        6,
        22
      ]
    ]
  },
  "references-count": 57,
  "journal-issue": {
    "issue": "7",
    "published-print": {
      "date-parts": [
        [
          2010,
          7
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1002/poc.1633"
  ],
  "URL": "http://dx.doi.org/10.1002/poc.1633",
  "relation": {},
  "ISSN": [
    "0894-3230",
    "1099-1395"
  ],
  "subject": [],
  "container-title-short": "J of Physical Organic Chem",
  "published": {
    "date-parts": [
      [
        2010,
        6,
        22
      ]
    ]
  }
}