Clinical Utility Of Creatine In Neurometabolic Disorders

There have been a number of small case series and case reports on the effects of creatine supplementation in mitochondrial cytopathies. A case report of an 18 year old with MELAS syndrome taking creatine at 12 g d for 12 days followed by 5g d for 28 months showed a definite improvement in MRI and MR spectroscopy values with an increase in brain creatine as well as marked behavior and cognitive improvements. There appeared to be a deterioration of renal function with an impairment of renal...

Future Directions

The current data appear to support the concept that CrM administration over a period of several months can increase muscle strength and enhance body composition in patients with muscular dystrophy. It will be important to determine whether these objective markers of muscle strength translate into functional improvements and, ultimately, a reduction in clinical severity markers (such as the time to wheelchair dependence in boys with Duchenne muscular dystrophy). Clearly, these clinical outcome...

Presymptomatic Treatment In A Gamtd Patient

GAMT-D (MIM 601240) is an autosomal-recessive inherited Cr synthesis defect and has the most severe phenotype among the Cr deficiency syndromes. Patients are clinically affected by mental retardation, lack of speech, autistic behaviour, extrapyramidal movement disorder, and epilepsy (sometimes refractory to therapeutic intervention) (Schulze, 2003). Cr deficiency and accumulation of GAA, the latter known for its neurotoxic and epileptogenic effects (da Silva et al., 1999 D'Hooge et al., 1992...

Mitochondrial Encephalopathies

Metabolic activity within the central nervous system is relatively high, making brain tissue especially vulnerable to mitochondrial respiratory chain abnormalities. Mitochondrial encephalopathies are multi-system diseases characterized by biochemical and genetic mitochondrial defects with differing clinical symptomatologies and brain area involvements. Mitochondrial encephalopathies are age-related with respect to disease onset, occurring mostly in infants and young children, but also in...

Series Editor

ROBIN HARRIS, University of Mainz, Mainz, Germany ASSISTANT EDITORS B.B. BISWAS, University of Calcutta, Calcutta, India P. QUINN, King's College London, London, U.K. Edited by Harald Herrmann and J. Robin Harris Volume 32 alpha-Gal and Anti-Gal alpha-1,3-Galactosyltransferase, alpha-Gal Epitopes and the Natural Anti-Gal Antibody Edited by Uri Galili and Jos-Luis Avila Volume 33 Bacterial Invasion into Eukaryotic Cells Tobias A. Oelschlaeger and Jorg Hacker Volume 34 Fusion of Biological...

References

Abraham, M.R., Selivanov, V.A., Hodgson, D.M., Pucar, D., Zingman, L.V., Wieringa, B., Dzeja P. Alekseev, A.E., and Terzic, A., 2002, Coupling of cell energetics with membrane metabolic sensing. Integrative signaling through creatine kinase phosphotransfer disrupted by M-CK gene knock-out. J. Biol. Chem. 277 24427-24434. Aliev, M.K., and Saks, V.A., 1997, Compartmentalised energy transfer in cardiomyocytes. Use of mathematical modeling for analysis of in vivo regulation of respiration. Biophys....

Conclusion Of Creatine Kinase

High Creatine Kinase

Our recent research provides novel molecular-anatomical evidence that (i) CRT at the BBB and iBRB is involved in regulating the creatine concentration in the brain and retina and that (ii) local creatine is preferentially synthesized in the glial cells in the brain and retina. These findings provide important information that will increase our understanding of the mechanism of creatine supply and creatine use in the brain and retina and of creatine supplementation in patients with creatine...

Creatine Supplementation In Neurodegenerative Disorders

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is characterized by progressive motor dysfunction, emotional disturbances, dementia, and weight loss. HD occurs worldwide, in all races and ethnic groups (Kremer et al., 1994). Its prevalence is 5-10 per 100,000, with a new mutation rate as high as 1-3 (Myers et al., 1993). There are about 30,000 affected individuals in the United States. Another 150,000 Americans have a genetic risk for developing the...

Ischemic Stroke

Stroke remains one of the major causes of death and a leading cause of functional impairment, resulting in long-term disability. The latter is manifest by neurological dysfunction and significant reduction in the ability to perform activities of daily living. There are greater than 20 million incident strokes worldwide each year, resulting in more than 5.5 million annual deaths World Health Report, 2002 . Ischemic stroke is by far the most prevalent, accounting for about 88 of all strokes....

Historical Aspects Of Creatine Kinase And Creatine

Functions of Creatine Kinase and Phosphocreatine in Muscle Contraction Historically, over the last century, the CK and Cr field went through alternating periods of excitement and depression, concerning new ideas and concepts of CK PCr Cr function, particularly in the area of muscle biochemistry. New discoveries related to the true function of PCr, the energy-rich version of Cr that had been discovered in 1927 simultaneously by Eggleton and Eggleton and by Fiske and Subbarow, met with great...

Substrate Specificity And Transport Mechanism Of The

The CRT is highly specific for creatine. Neither creatinine nor phosphocreatine are substrates. The key features for substrate specificity are a carboxyl group and a guanidino group, separated by no more than 2-3 carbon atoms Guimbal and Kilimann, 1993 Moller and Hamprecht, 1989 Saltarelli et al., 1996 Sora et al., 1994 . A benzyl ester derivative of creatine which no longer contains a free carboxyl group is not a substrate for the transporter although it can be taken up by brain slices in a...