Creatine kinase



Creatine phosphate figure B.98 Phosphorylation by creatine kinase

(EC3.1.3.0). A normally minor metabolic pathway is the conversion first into melhy-lamine and then into formaldehyde. This route bccomcs more significant when several grams of creatine are consumed with supplements (Yu and Deng. 20001.

Both creatine and creatine phosphate decompose non-en/ymically to creatinine. About 1.1% of the creatine in the body is thus concerted to creatinine, and about 2.6% of the phosphocrcatine (Wyss and Kaddurah-Daouk. 2000). The rate of creatinine generation correlates well with muscle mass, since this is where most of the more easily decomposing phosphocrcatine resides.

There has been the suggestion that some creatinine may be tnetabolieally recovered (Boroujerdi and Mattocks, 1983), but supportive evidence is limited.

While much of the body's creatine is in muscle (0.3 0.5% of muscle weight; Crim and Munro, 1994), several other tissues also contain high concentrations (Wyss and Kaddurah-Daouk, 2000). Very high intake (20g/d) slightly increases creatine concentration in skeletal muscle 11 15%; Smith et «/.. 1909) and also in brain (+9%; Dechent etal.. 1999).


A high-affinity sodium-de pendent creatine transporter with a 2:1 sodium xreatinc transport ratio recovers creatine, but not creatinine, very efficiently from the proximal tubular lumen in the kidneys (Wyss and Kaddurah-Daouk. 2000).

F iguiK.t|" Creatinine arises from creatine phosphate and crcalme


More tlian a grain of creatinine is filtered daily in the kidneys. Little of this is reabsorbed and there is no significant secretion into the tubular lumen as long as renal function is normal. Since the production rate of creatinine is reasonably constant, it is common clinical practice to use the creatinine concentration in plasma as an approximate indicator of the glomerular filtration rate (GFR). Greatly increased plasma creatinine concentration invariably indicates diminished filtration function and renal failure.

Daily creatinine excretion with urine is about 15mg/kg body weight or about 1,7".. of creatine body stores (Forbes and Braining, 1976).


High creatine intake does not greatly increase plasma creatinine concentration, and increases only the excretion of creatine, not of creatinine (Poortmans and Francaux. 1999).

Inhibition of expression and activity of glycine amidinotransfcrase (EC2.1 .-4.1) by its down-stream product creatine appear to be the major regulatory events that control endogenous creatine synthesis (Wyss and Kaddurah-Daouk. 2000). Thyroxin and growth hormone stimulate this rate-limiting step, low energy intake and vitamin E deficiency slow it down. The regulation of creatine synthesis in brain, pancreas, testis, and other tissues is largely autonomous and independent of bulk production rates in kidneys and liver.


Creatine phosphate is the main high-energy, phosphate-storage molecule of muscle. In rested muscle creatine phosphate is the predominant form (Deniant and Rhodes, 1999); its maximal concentration is five times higher than that of ATP. During times of acute energy need the creatine kinase (EC2.73.2) uses creatine phosphate for the ultrarapid phosphorylation of ADP to ATP. Spermatozoa and photoreceptor cells of the eyes also appear to critically depend on creatine phosphate.

Creatine phosphate may be equally important as a stabilizing energy source in brain. It has been suggested high energy phosphates help to maintain membrane potentials, participate in neurotransmitter release, contribute to calcium homeostasis, and play roles in neuronal migration, surv ival and apoptosis (Wyss and kaddurah-Daouk. 2000). Creatine is a required cofactorof adcnosylate kinase (EC2.7,4.3) and other enzymes.


Boroujerdi M. Mattocks AM. Metabolism of creatinine in vivo. Clin Ctiem 1983;29:1363-6 Crim MC, Munro HN. Proteins and amino acids. In Shils ME. Olson JA, Shike M, eds Modern Nutrition in Health ami Disease. Lea & Fchiger, Philadelphia, 1094. pp.3 35 Deehent P. Pouvvels PJ. Wilken li. Hanefcld F. Frahm J. Increase of total creatine in human brain after oral supplementation of cieatine-nionohydrate. Am J Physiol 1949; 277:R698-R704

Demant TW, Rhodes EC. Effects of creatine supplementation on exercise performance. Sports Medicine 1999;28:49-60

l:orbcs CJ13. IJruining GJ. Urinary creatinine excretion and lean body mass. Am J dm Suit 1976;29:1359-66

(Jguri A. Suda M, Totsuka V, Sugimura T. Wakabayashi k. Inhibitory effects of antioxidants on formation of heterocyclic amines. Mut Res 1998:402:237 45 Pöortmans JR. Francanx M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Spans Ex 1999^1:1108 10 Schloss P. Mavscr W. Ret/ H. The putative rat choline transporter chot I transports creatine and is highly expressed in neural and muscle-rich tissues. Biochem Biophys Res Comm 1994:198:637 45

Schul HA, Snyderwine EG. DNA adducts of heterocyclic amine ibod mutagens: implications for mutagenesis and carcinogenesis. Carcinogenesis 1999:20:353 f>8 Smith SA, Montain SJ. Matott RP. /icntara GP, Jolesz FA, Fielding RA. Effects of creatine supplementation on the energy cost of muscle contraction: a 31P-MRS study. JApplPhytsiol 1999:87:116 23 Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism, Physiol Rei 2000; 1107-213

Yu !'l I. Deng V. Potential cytotoxic effect of chronic administration of creatine, a nutrition supplement to augment athletic performance. Med Hypotheses 2000:54:726- 8

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