肌酸激酶的生理功能与运动
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摘要
肌酸激酶(creatine kinase,CK)是催化磷酸肌酸和ATP间高能磷酸基团转移的关键酶,它保持ATP/ADP比例平衡和ATP的供给。肌酸激酶家族共有5种同工酶,分布于全身各种组织的需能部位。研究发现,CK酶在能量代谢中有重要作用,与肌肉收缩、神经功能、细胞膜的稳定性、细胞的能量反馈调节、有氧耐力有关。一些研究认为,CKM(肌型肌酸激酶,creatine kinase,muscle)基因多态性影响个体有氧运动能力和个体对耐力训练的敏感性。本文对这些成果作一综述,并对未来研究进行展望,以期为进一步的研究提供参考。
The creatine kinase( CK) is a key enzyme which catalyzes the transfer of high-energy phosphates between PCr and ATP,thus keeping cellular ATP-to-ADP ratios balanced and the ATP pool highly charged. Five isoenzymes in CK family were expressed in regions consuming energy all over different tissues. Many experimental studies have revealed that CK may play important role during energy metabolism,and they were associated with muscle contraction,neurological function,stability of membranal,feedback regulation of energy metabolism and aerobic endurance performance. Other studies found that CKMM gene polymorphisms may contribute to individual aerobic endurance and its' sensibility to endurance training. The purpose of this work is to provide a new background for the people who are studying in this field by attempting to analyze these results,and inspire future researches.
The creatine kinase( CK) is a key enzyme which catalyzes the transfer of high-energy phosphates between PCr and ATP,thus keeping cellular ATP-to-ADP ratios balanced and the ATP pool highly charged. Five isoenzymes in CK family were expressed in regions consuming energy all over different tissues. Many experimental studies have revealed that CK may play important role during energy metabolism,and they were associated with muscle contraction,neurological function,stability of membranal,feedback regulation of energy metabolism and aerobic endurance performance. Other studies found that CKMM gene polymorphisms may contribute to individual aerobic endurance and its' sensibility to endurance training. The purpose of this work is to provide a new background for the people who are studying in this field by attempting to analyze these results,and inspire future researches.
引文
[1]Wallimann T,Tokarska-Schlattner M,Schlattner U.The creatine kinase system and pleiotropic effects of creatine[J].Amino Acids,2011,40:1271-1296.
[2]Wallimann T,Tokarska-Schlattner M,Neumann D,et al.The phospho-creatine circuit:molecular and cellular physiology of creatine kinases,sensitivity to free radicals and enhancement by creatine supplementation.In:Saks VA(ed)Molecular systems bioenergetics:energy for life[M].Wiley,Weinheim,2007:195–264.
[3]Rankinen T RS,Bray MS,Loos R,et al.Advances in exercise,fitness,and performance genomics[J].Med Sci Sports Exerc,2010,42(5):835-846.
[4]Zhou DQ,Hu Y,Liu G,et al.Muscle-specific creatine kinase gene polymorphism and running economy responses to an 18-week5000-m training programme[J].Br J Sports Med,2006,40(12):988-991.
[5]Kresge N,Simoni RD,Hill RL.Otto Fritz Meyerhof and the elucidation of the glycolytic pathway[J].J Biol Chem,2005,280(4):e3.
[6]Guzun WR,Timohhina N,Tepp K,et al.Systems bioenergetics of creatine kinase networks:physiological roles of creatine and phosphocreatine in regulation of cardiac cell function[J].Amino Acids,2011,40:1271-1296.
[7]Saks V,Monge C,Anmann T,et al.Integrated and organized cellular energetic systems:theories of cell energetics,compartmentation and metabolic channelling.In:Saks V(ed)Molecular system bioenergetics[M].Energy for life,Wiley-VCH,2007.
[8]Saks VA,Rosenshtraukh LV,Smirnov VN,et al.Role of creatine phospliokinase in cellular function and metabolism[J].Can J Physiol Pharmacol,1978,56(5):691-706.
[9]Miller K.Halow J,Koretsky AP.Phosphocreatine protects transgenic mouse liver expressing creatine kinase from hypoxia and ischemia[J].Am J Physiol,1993,265:C1544-C1551.
[10]Turner DC,Wallimann T,Eppenberger HM.A protein that binds specifically to the M-line of skeletal muscle is identified as the muscle form of creatine kinase[J].Proc Natl Acad Sci USA,1973,70:702-705.
[11]Wegmann G,Huber R,Zanolla E,et al.Differential expression and localization of brain-type and mitochondrial creatine kinase isoenzymes during development of the chicken retina:Mi-CK as a marker for differentiation of photoreceptor ceils[J].Differentiation,1991,46(2):77-87.
[12]Korge P,Camphc Il KB.Local ATP regeneration is important for sarcoplasmic rcticulum Ca2+pump function[J].Am J Physiol,1994,267:C357-C366.
[13]Saks VA,Kuznetzov AV,Kupriyanov VV,et al.Creatine kinase of rat heart mitochondria:the demonstration of functional coupling to oxidative phosphorylalion in an inner membrane preparation[J].J Biol Chcm,1985,260:7757-64.
[14]Saks V,Beraud N,Wallimann T.Metabolic compartmentation—a system level property of muscle cells[J].Int J Mol Sci,2008,9:751–767.
[15]Echegaray M,Rivera MA.Role of creatine kinase isoenzymes on muscular and cardiorespiratory endurance[J].Genetic and Molecular Evidence,2001,31(13):919-934.
[16]Guerrero-Ontiveros ML,Wa Iliman T.Creatine supplementation in health and disease.Effects of chronic creatine ingestion in vivor:down regulation of the expression of creatine kinase transporter isoiforms in skeletal muscle[J].Mol Cell Biochem,1998,184:427-37.
[17]Rico Sanz J,Mendez,Marco MT.Creatine enhances oxygen uptake and performance during alternating intensity exercise[J].Med Sci Sports Exerc,2000,32(2):379-85.
[18]Guzun R,Timohhina N,Tepp K,et al.Regulation of respiration controlled by mitochondrial creatine kinase in permeabilized cardiac cells in situ.Importance of system level properties[J].Biochim Biophys Acta,2009,1787:1089–1105.
[19]Carolina RJ,Catharina EE,Vander Z,et al.Creatine kinase Bdriven energy transfer in the brain is important for habituation and spatial learning behaviour,mossy fibre field size and determination of seizure susceptibility[J].European Journal of Neuroscience,2002,15:1692-1706.
[20]Femke S,Carolina RJ,Frank O,et al.Mice lacking the Ub CKmit isoform of creatine kinase reveal slower spatial learning acquisition,diminished exploration and habituation,and reduced acoustic startle reflex responses[J].Molecular and Cellular Biochemistry,2004,256:305-318.
[21]Femke S,Frank O,Bart A,et al.Structural and behavioural consequences of double deficiency for creatine kinases BCK and Ub CKmit[J].Behavioural Brain Research,2005,157:219-234.
[22]Saks V,Strumia E.Phosphocreatine:Molecular and cellular aspects of the mechanism of cardioprotective action[J].Curr Therapeut Res,1993,53:565-598.
[23]Yamashita,K,Yoshioka T.Profiles of creatine kinase isoenzyme compositions in single muscle fibers of different types[J].J Muscle Res Cell Motil,1991,12:37-44.
[24]Van Deursen J,Heerschap A,Oerlemans F.Skeletal muscles of mice deficient in M-creatine kinase lack burst activity[J].Cell,1993,74:621-631.
[25]VAN Deursen J,Ruitenbeek W,Heerschap A,et al.Creatine kinase in muscle energy metabolism:a study of mouse mutants with graded reduction in CK expression[J].Proc Natl Acad Sci USA,1994,91:9091-9095.
[26]Apple P S,Billardello JJ.Expression ol'creatine kinase M and B mRNAs in treadmill trained rat skeletal muscle[J].Life Sci,1994,55(8):585-92.
[27]Alam M,Vaynhlat M,Goswami SK,et al.Activation of creatine kinase-B and phospliolanihan gene expression in transformed latissinius dorsi muscle:evaluation of mRNA by polymerase chain reaction[J].J Mol Cell Carcliol,1996,28(9):1901-1901.
[28]Tsika RW,Hauschka SD,Gao L.M-crcatinc kinase gene expression in mechanically overloaded skeletal muscle of transgenic mice[J].Am J Physiol,1995,269:C665-C674.
[29]Bouchard C,Wolfarth B,Rivcra MA,et al.Genetic determinants of endurance performance.In:Shephard R.I,Astrand PO.editor.Endurance in sports[M].2nd ed.London:Blackwell Science,2000,223-243.
[30]Rivera MA,Dionne FT,Simoneau JA,et al.Muscle-specific creatine kinase gene polymorphism and VO2maxin the Heritage family study[J].Med Sci Sports Exerc,1997,29(10):1311-1317.
[31]Rivera MA,Perusse JA,Simoneau J,et al.Linkage between a muscle-specific CK gene marker and VO2maxin the HERITAGE Family Study[J].Med Sci Sports Exerc,1999,31:698-701.
[32]Fedotovskaia ON,Popov DV,Vinogradova OL,et al.Association of the muscle-specific creatine kinase(CKMM)gene polymorphism with physical performance of athletes[J].Fiziol Cheloveka,2012,38(1):105-109.
[33]Rivera M A,Dionne F T,Wolfarth B,et al.Muscle-specific creatine Kinase gene polymorphisms in elite endurance athletes and sedentary controls[J].Med Sci Sports Exerc,1997,29(11):1444-1447.
[34]Byung,Yong Kang,et al.Muscle specific creatine kinase gene polymorphisms in korean elite athletes[J].J Toxicol Pub Health,2003,19(2):115-121.
[35]Robert S,Cristina M,Barreda M,et al.Association between CKMM genotype and endurance performance level in hispanic marathon runners[J].Med Sci Sports Exerc,2004,36(5)Supplement:S260.
[36]Lucía A,Gómez-Gallego F,Chicharro JL,et al.Is there an association between ACE and CKMM polymorphisms and cycling performance status during 3-week races?[J].Int J Sports Med,2005,26(6):442-447.
[37]Defoor J,Martens K,Matthijs G,et al.The caregene study:muscle-specific creatine kinase gene and aerobic power in coronary artery disease[J].Eur J Cardiovasc Prev Rehabil,2005,12(4):415-417.
[2]Wallimann T,Tokarska-Schlattner M,Neumann D,et al.The phospho-creatine circuit:molecular and cellular physiology of creatine kinases,sensitivity to free radicals and enhancement by creatine supplementation.In:Saks VA(ed)Molecular systems bioenergetics:energy for life[M].Wiley,Weinheim,2007:195–264.
[3]Rankinen T RS,Bray MS,Loos R,et al.Advances in exercise,fitness,and performance genomics[J].Med Sci Sports Exerc,2010,42(5):835-846.
[4]Zhou DQ,Hu Y,Liu G,et al.Muscle-specific creatine kinase gene polymorphism and running economy responses to an 18-week5000-m training programme[J].Br J Sports Med,2006,40(12):988-991.
[5]Kresge N,Simoni RD,Hill RL.Otto Fritz Meyerhof and the elucidation of the glycolytic pathway[J].J Biol Chem,2005,280(4):e3.
[6]Guzun WR,Timohhina N,Tepp K,et al.Systems bioenergetics of creatine kinase networks:physiological roles of creatine and phosphocreatine in regulation of cardiac cell function[J].Amino Acids,2011,40:1271-1296.
[7]Saks V,Monge C,Anmann T,et al.Integrated and organized cellular energetic systems:theories of cell energetics,compartmentation and metabolic channelling.In:Saks V(ed)Molecular system bioenergetics[M].Energy for life,Wiley-VCH,2007.
[8]Saks VA,Rosenshtraukh LV,Smirnov VN,et al.Role of creatine phospliokinase in cellular function and metabolism[J].Can J Physiol Pharmacol,1978,56(5):691-706.
[9]Miller K.Halow J,Koretsky AP.Phosphocreatine protects transgenic mouse liver expressing creatine kinase from hypoxia and ischemia[J].Am J Physiol,1993,265:C1544-C1551.
[10]Turner DC,Wallimann T,Eppenberger HM.A protein that binds specifically to the M-line of skeletal muscle is identified as the muscle form of creatine kinase[J].Proc Natl Acad Sci USA,1973,70:702-705.
[11]Wegmann G,Huber R,Zanolla E,et al.Differential expression and localization of brain-type and mitochondrial creatine kinase isoenzymes during development of the chicken retina:Mi-CK as a marker for differentiation of photoreceptor ceils[J].Differentiation,1991,46(2):77-87.
[12]Korge P,Camphc Il KB.Local ATP regeneration is important for sarcoplasmic rcticulum Ca2+pump function[J].Am J Physiol,1994,267:C357-C366.
[13]Saks VA,Kuznetzov AV,Kupriyanov VV,et al.Creatine kinase of rat heart mitochondria:the demonstration of functional coupling to oxidative phosphorylalion in an inner membrane preparation[J].J Biol Chcm,1985,260:7757-64.
[14]Saks V,Beraud N,Wallimann T.Metabolic compartmentation—a system level property of muscle cells[J].Int J Mol Sci,2008,9:751–767.
[15]Echegaray M,Rivera MA.Role of creatine kinase isoenzymes on muscular and cardiorespiratory endurance[J].Genetic and Molecular Evidence,2001,31(13):919-934.
[16]Guerrero-Ontiveros ML,Wa Iliman T.Creatine supplementation in health and disease.Effects of chronic creatine ingestion in vivor:down regulation of the expression of creatine kinase transporter isoiforms in skeletal muscle[J].Mol Cell Biochem,1998,184:427-37.
[17]Rico Sanz J,Mendez,Marco MT.Creatine enhances oxygen uptake and performance during alternating intensity exercise[J].Med Sci Sports Exerc,2000,32(2):379-85.
[18]Guzun R,Timohhina N,Tepp K,et al.Regulation of respiration controlled by mitochondrial creatine kinase in permeabilized cardiac cells in situ.Importance of system level properties[J].Biochim Biophys Acta,2009,1787:1089–1105.
[19]Carolina RJ,Catharina EE,Vander Z,et al.Creatine kinase Bdriven energy transfer in the brain is important for habituation and spatial learning behaviour,mossy fibre field size and determination of seizure susceptibility[J].European Journal of Neuroscience,2002,15:1692-1706.
[20]Femke S,Carolina RJ,Frank O,et al.Mice lacking the Ub CKmit isoform of creatine kinase reveal slower spatial learning acquisition,diminished exploration and habituation,and reduced acoustic startle reflex responses[J].Molecular and Cellular Biochemistry,2004,256:305-318.
[21]Femke S,Frank O,Bart A,et al.Structural and behavioural consequences of double deficiency for creatine kinases BCK and Ub CKmit[J].Behavioural Brain Research,2005,157:219-234.
[22]Saks V,Strumia E.Phosphocreatine:Molecular and cellular aspects of the mechanism of cardioprotective action[J].Curr Therapeut Res,1993,53:565-598.
[23]Yamashita,K,Yoshioka T.Profiles of creatine kinase isoenzyme compositions in single muscle fibers of different types[J].J Muscle Res Cell Motil,1991,12:37-44.
[24]Van Deursen J,Heerschap A,Oerlemans F.Skeletal muscles of mice deficient in M-creatine kinase lack burst activity[J].Cell,1993,74:621-631.
[25]VAN Deursen J,Ruitenbeek W,Heerschap A,et al.Creatine kinase in muscle energy metabolism:a study of mouse mutants with graded reduction in CK expression[J].Proc Natl Acad Sci USA,1994,91:9091-9095.
[26]Apple P S,Billardello JJ.Expression ol'creatine kinase M and B mRNAs in treadmill trained rat skeletal muscle[J].Life Sci,1994,55(8):585-92.
[27]Alam M,Vaynhlat M,Goswami SK,et al.Activation of creatine kinase-B and phospliolanihan gene expression in transformed latissinius dorsi muscle:evaluation of mRNA by polymerase chain reaction[J].J Mol Cell Carcliol,1996,28(9):1901-1901.
[28]Tsika RW,Hauschka SD,Gao L.M-crcatinc kinase gene expression in mechanically overloaded skeletal muscle of transgenic mice[J].Am J Physiol,1995,269:C665-C674.
[29]Bouchard C,Wolfarth B,Rivcra MA,et al.Genetic determinants of endurance performance.In:Shephard R.I,Astrand PO.editor.Endurance in sports[M].2nd ed.London:Blackwell Science,2000,223-243.
[30]Rivera MA,Dionne FT,Simoneau JA,et al.Muscle-specific creatine kinase gene polymorphism and VO2maxin the Heritage family study[J].Med Sci Sports Exerc,1997,29(10):1311-1317.
[31]Rivera MA,Perusse JA,Simoneau J,et al.Linkage between a muscle-specific CK gene marker and VO2maxin the HERITAGE Family Study[J].Med Sci Sports Exerc,1999,31:698-701.
[32]Fedotovskaia ON,Popov DV,Vinogradova OL,et al.Association of the muscle-specific creatine kinase(CKMM)gene polymorphism with physical performance of athletes[J].Fiziol Cheloveka,2012,38(1):105-109.
[33]Rivera M A,Dionne F T,Wolfarth B,et al.Muscle-specific creatine Kinase gene polymorphisms in elite endurance athletes and sedentary controls[J].Med Sci Sports Exerc,1997,29(11):1444-1447.
[34]Byung,Yong Kang,et al.Muscle specific creatine kinase gene polymorphisms in korean elite athletes[J].J Toxicol Pub Health,2003,19(2):115-121.
[35]Robert S,Cristina M,Barreda M,et al.Association between CKMM genotype and endurance performance level in hispanic marathon runners[J].Med Sci Sports Exerc,2004,36(5)Supplement:S260.
[36]Lucía A,Gómez-Gallego F,Chicharro JL,et al.Is there an association between ACE and CKMM polymorphisms and cycling performance status during 3-week races?[J].Int J Sports Med,2005,26(6):442-447.
[37]Defoor J,Martens K,Matthijs G,et al.The caregene study:muscle-specific creatine kinase gene and aerobic power in coronary artery disease[J].Eur J Cardiovasc Prev Rehabil,2005,12(4):415-417.