The creatine kinase system and pleiotropic effects of creatine
Identifieur interne : 000661 ( Pmc/Checkpoint ); précédent : 000660; suivant : 000662The creatine kinase system and pleiotropic effects of creatine
Auteurs : Theo Wallimann [Suisse] ; Malgorzata Tokarska-Schlattner [France] ; Uwe Schlattner [France]Source :
- Amino Acids [ 0939-4451 ] ; 2011.
Abstract
The pleiotropic effects of creatine (Cr) are based mostly on the functions of the enzyme creatine kinase (CK) and its high-energy product phosphocreatine (PCr). Multidisciplinary studies have established molecular, cellular, organ and somatic functions of the CK/PCr system, in particular for cells and tissues with high and intermittent energy fluctuations. These studies include tissue-specific expression and subcellular localization of CK isoforms, high-resolution molecular structures and structure–function relationships, transgenic CK abrogation and reverse genetic approaches. Three energy-related physiological principles emerge, namely that the CK/PCr systems functions as (a) an immediately available temporal energy buffer, (b) a spatial energy buffer or intracellular energy transport system (the CK/PCr energy shuttle or circuit) and (c) a metabolic regulator. The CK/PCr energy shuttle connects sites of ATP production (glycolysis and mitochondrial oxidative phosphorylation) with subcellular sites of ATP utilization (ATPases). Thus, diffusion limitations of ADP and ATP are overcome by PCr/Cr shuttling, as most clearly seen in polar cells such as spermatozoa, retina photoreceptor cells and sensory hair bundles of the inner ear. The CK/PCr system relies on the close exchange of substrates and products between CK isoforms and ATP-generating or -consuming processes. Mitochondrial CK in the mitochondrial outer compartment, for example, is tightly coupled to ATP export via adenine nucleotide transporter or carrier (ANT) and thus ATP-synthesis and respiratory chain activity, releasing PCr into the cytosol. This coupling also reduces formation of reactive oxygen species (ROS) and inhibits mitochondrial permeability transition, an early event in apoptosis. Cr itself may also act as a direct and/or indirect anti-oxidant, while PCr can interact with and protect cellular membranes. Collectively, these factors may well explain the beneficial effects of Cr supplementation. The stimulating effects of Cr for muscle and bone growth and maintenance, and especially in neuroprotection, are now recognized and the first clinical studies are underway. Novel socio-economically relevant applications of Cr supplementation are emerging, e.g. for senior people, intensive care units and dialysis patients, who are notoriously Cr-depleted. Also, Cr will likely be beneficial for the healthy development of premature infants, who after separation from the placenta depend on external Cr. Cr supplementation of pregnant and lactating women, as well as of babies and infants are likely to be of benefit for child development. Last but not least, Cr harbours a global ecological potential as an additive for animal feed, replacing meat- and fish meal for animal (poultry and swine) and fish aqua farming. This may help to alleviate human starvation and at the same time prevent over-fishing of oceans.
Url:
DOI: 10.1007/s00726-011-0877-3
PubMed: 21448658
PubMed Central: 3080659
Affiliations:
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PMC:3080659Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>The pleiotropic effects of creatine (Cr) are based mostly on the functions of the enzyme creatine kinase (CK) and its high-energy product phosphocreatine (PCr). Multidisciplinary studies have established molecular, cellular, organ and somatic functions of the CK/PCr system, in particular for cells and tissues with high and intermittent energy fluctuations. These studies include tissue-specific expression and subcellular localization of CK isoforms, high-resolution molecular structures and structure–function relationships, transgenic CK abrogation and reverse genetic approaches. Three energy-related physiological principles emerge, namely that the CK/PCr systems functions as (a) an immediately available temporal energy buffer, (b) a spatial energy buffer or intracellular energy transport system (the CK/PCr energy shuttle or circuit) and (c) a metabolic regulator. The CK/PCr energy shuttle connects sites of ATP production (glycolysis and mitochondrial oxidative phosphorylation) with subcellular sites of ATP utilization (ATPases). Thus, diffusion limitations of ADP and ATP are overcome by PCr/Cr shuttling, as most clearly seen in polar cells such as spermatozoa, retina photoreceptor cells and sensory hair bundles of the inner ear. The CK/PCr system relies on the close exchange of substrates and products between CK isoforms and ATP-generating or -consuming processes. Mitochondrial CK in the mitochondrial outer compartment, for example, is tightly coupled to ATP export via adenine nucleotide transporter or carrier (ANT) and thus ATP-synthesis and respiratory chain activity, releasing PCr into the cytosol. This coupling also reduces formation of reactive oxygen species (ROS) and inhibits mitochondrial permeability transition, an early event in apoptosis. Cr itself may also act as a direct and/or indirect anti-oxidant, while PCr can interact with and protect cellular membranes. Collectively, these factors may well explain the beneficial effects of Cr supplementation. The stimulating effects of Cr for muscle and bone growth and maintenance, and especially in neuroprotection, are now recognized and the first clinical studies are underway. Novel socio-economically relevant applications of Cr supplementation are emerging, e.g. for senior people, intensive care units and dialysis patients, who are notoriously Cr-depleted. Also, Cr will likely be beneficial for the healthy development of premature infants, who after separation from the placenta depend on external Cr. Cr supplementation of pregnant and lactating women, as well as of babies and infants are likely to be of benefit for child development. Last but not least, Cr harbours a global ecological potential as an additive for animal feed, replacing meat- and fish meal for animal (poultry and swine) and fish aqua farming. This may help to alleviate human starvation and at the same time prevent over-fishing of oceans.</p>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Amino Acids</journal-id>
<journal-title-group><journal-title>Amino Acids</journal-title>
</journal-title-group>
<issn pub-type="ppub">0939-4451</issn>
<issn pub-type="epub">1438-2199</issn>
<publisher><publisher-name>Springer Vienna</publisher-name>
<publisher-loc>Vienna</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21448658</article-id>
<article-id pub-id-type="pmc">3080659</article-id>
<article-id pub-id-type="publisher-id">877</article-id>
<article-id pub-id-type="doi">10.1007/s00726-011-0877-3</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Invited Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>The creatine kinase system and pleiotropic effects of creatine</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Wallimann</surname>
<given-names>Theo</given-names>
</name>
<address><phone>+41-44-7407047</phone>
<fax>+41-44-7413008</fax>
<email>theo.wallimann@cell.biol.ethz.ch</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tokarska-Schlattner</surname>
<given-names>Malgorzata</given-names>
</name>
<address><phone>+33-476-514671</phone>
<fax>+33-476-514218</fax>
<email>malgorzata.tokarska-schlattner@ujf-grenoble.fr</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schlattner</surname>
<given-names>Uwe</given-names>
</name>
<address><phone>+33-476-514671</phone>
<fax>+33-476-514218</fax>
<email>uwe.schlattner@ujf-grenoble.fr</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<aff id="Aff1"><label>1</label>
Institute of Cell Biology, ETH Zurich, Zurich, Switzerland</aff>
<aff id="Aff2"><label>2</label>
INSERM U1055 and University Joseph Fourier Grenoble 1, Laboratory of Fundamental and Applied Bioenergetics, BP 53, 38041 Grenoble cedex 9, France</aff>
<aff id="Aff3"><label>3</label>
Schürmattstrasse 23, 8962 Bergdietikon, AG Switzerland</aff>
</contrib-group>
<pub-date pub-type="epub"><day>30</day>
<month>3</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>30</day>
<month>3</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><month>5</month>
<year>2011</year>
</pub-date>
<volume>40</volume>
<issue>5</issue>
<fpage>1271</fpage>
<lpage>1296</lpage>
<history><date date-type="received"><day>10</day>
<month>7</month>
<year>2010</year>
</date>
<date date-type="accepted"><day>2</day>
<month>12</month>
<year>2010</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s) 2011</copyright-statement>
</permissions>
<abstract id="Abs1"><p>The pleiotropic effects of creatine (Cr) are based mostly on the functions of the enzyme creatine kinase (CK) and its high-energy product phosphocreatine (PCr). Multidisciplinary studies have established molecular, cellular, organ and somatic functions of the CK/PCr system, in particular for cells and tissues with high and intermittent energy fluctuations. These studies include tissue-specific expression and subcellular localization of CK isoforms, high-resolution molecular structures and structure–function relationships, transgenic CK abrogation and reverse genetic approaches. Three energy-related physiological principles emerge, namely that the CK/PCr systems functions as (a) an immediately available temporal energy buffer, (b) a spatial energy buffer or intracellular energy transport system (the CK/PCr energy shuttle or circuit) and (c) a metabolic regulator. The CK/PCr energy shuttle connects sites of ATP production (glycolysis and mitochondrial oxidative phosphorylation) with subcellular sites of ATP utilization (ATPases). Thus, diffusion limitations of ADP and ATP are overcome by PCr/Cr shuttling, as most clearly seen in polar cells such as spermatozoa, retina photoreceptor cells and sensory hair bundles of the inner ear. The CK/PCr system relies on the close exchange of substrates and products between CK isoforms and ATP-generating or -consuming processes. Mitochondrial CK in the mitochondrial outer compartment, for example, is tightly coupled to ATP export via adenine nucleotide transporter or carrier (ANT) and thus ATP-synthesis and respiratory chain activity, releasing PCr into the cytosol. This coupling also reduces formation of reactive oxygen species (ROS) and inhibits mitochondrial permeability transition, an early event in apoptosis. Cr itself may also act as a direct and/or indirect anti-oxidant, while PCr can interact with and protect cellular membranes. Collectively, these factors may well explain the beneficial effects of Cr supplementation. The stimulating effects of Cr for muscle and bone growth and maintenance, and especially in neuroprotection, are now recognized and the first clinical studies are underway. Novel socio-economically relevant applications of Cr supplementation are emerging, e.g. for senior people, intensive care units and dialysis patients, who are notoriously Cr-depleted. Also, Cr will likely be beneficial for the healthy development of premature infants, who after separation from the placenta depend on external Cr. Cr supplementation of pregnant and lactating women, as well as of babies and infants are likely to be of benefit for child development. Last but not least, Cr harbours a global ecological potential as an additive for animal feed, replacing meat- and fish meal for animal (poultry and swine) and fish aqua farming. This may help to alleviate human starvation and at the same time prevent over-fishing of oceans.</p>
</abstract>
<kwd-group><title>Keywords</title>
<kwd>Creatine kinase isoforms</kwd>
<kwd>Microcompartments</kwd>
<kwd>Beneficial effects of creatine supplementation</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© Springer-Verlag 2011</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>France</li>
<li>Suisse</li>
</country>
<region><li>Auvergne-Rhône-Alpes</li>
<li>Rhône-Alpes</li>
</region>
<settlement><li>Grenoble</li>
</settlement>
</list>
<tree><country name="Suisse"><noRegion><name sortKey="Wallimann, Theo" sort="Wallimann, Theo" uniqKey="Wallimann T" first="Theo" last="Wallimann">Theo Wallimann</name>
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<country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Tokarska Schlattner, Malgorzata" sort="Tokarska Schlattner, Malgorzata" uniqKey="Tokarska Schlattner M" first="Malgorzata" last="Tokarska-Schlattner">Malgorzata Tokarska-Schlattner</name>
</region>
<name sortKey="Schlattner, Uwe" sort="Schlattner, Uwe" uniqKey="Schlattner U" first="Uwe" last="Schlattner">Uwe Schlattner</name>
</country>
</tree>
</affiliations>
</record>
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