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Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer -typically found in the heart 5 Isoforms Know in the Body Mitochondrial (30% of enzymatic activity) 4.) Sarcomeric type ( s mtCK) -octamer 5.) Ubiquitous type ( u mtCK) -octamer Blum, H. E., Deus, B., and Gerok, W. (1983) Mitochondrial creatine kinase from human heart: purification and characterization of crystallized isoenzyme. J. Biol. Chem. 94, 1247-1257.
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Pathway Tokasarska-Schlattner, M., Williann, T. (2006) Mitochondrial creatine kinase in human health and disease. Mol Bas. Dise. Vol 176, Iss 2, 164-180.
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Amino Acid Sequence Alignment -Methionine 273 -Cysteine 284 -Tryptophan 211, 218, and 228 Lyzlova, S. N., Stefanov, V. E. (1990) Phosphagen Kinases. CRC Press, 63-73 pgs.
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-Methionine 273 -Cysteine 284 Amino Acid Sequence Alignment
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-Tryptophan 211, 218, and 228
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Structure -13-18 alpha helicies depending on specific structure -32-38% alpha helix residues -16-19 beta sheets -15-16% -Human CK-BB -Contains -19 alpha helices (38%) -18 beta sheets (16%) PDB id = 3DRB Bong, S. M., Chi, Y. M., Hwang, K. Y., Lee, K. S., Moon, J. H., and Nam, K. H. (2008) Structural studies of human brain-type creatine kinase complexed with ADP- Mg 2+ -NO 3— creatine trasition- state analogue complex. FEBS Lett. 582, 28, 3959-3965.
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Transition Complex -Green loop interactions close off active site -Arg 130,132,236,292,320 create a positive pocket for phosphate of ATP/ADP to bind -Creatine’s carboxylate forms a H-bond with main chain N from Val72 -Cys283 anchors creatine for nucleophilic attach of a phosphorus from ATP Bong, S. M., Chi, Y. M., Hwang, K. Y., Lee, K. S., Moon, J. H., and Nam, K. H. (2008) Structural studies of human brain-type creatine kinase complexed with ADP-Mg 2+ -NO 3— creatine trasition-state analogue complex. FEBS Lett. 582, 28, 3959-3965.
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Creatine Kinase Test -Typical cardiac marker - During myocardia infarction cell contents is expelled -Can be an indicator of several other health issues -Depends on what isoform is elevated in the blood -Stroke, pulmonary infection, muscular dystrophies, myopathy, and others "Creatine Kinase, Serum." Mayo Clinic Mayo Medical Laboratories. January 1, 1999. Accessed October 19, 2014. http://www.mayomedicallaboratories.com/test-catalog/Clinical and Interpretive/8336.
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Creatine Supplementation -Can be utilized for short burst of energy for athletes -Strength and Endurance -Parkinson’s (slow symptoms) -Precautions??? "Creatine." Medline Plus. September 8, 2014. Accessed October 19, 2014. http://www.nlm.nih.gov/medlineplus/druginfo/natural/873.html.
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Delivery Methods -Creatine Monohydrate -Bound to one water molecule -Micronized Creatine -increased ingestion of creatine monohydrate -Creatine Ethy Ester -Ester aids in passing through the membrane -Creatine Malate -Contins 2-3 creatines attached to malic acid. Encourages energy transport -Creatine Hydrochoride -More soluble -Creatine Phosphate (phospocreatine) -not proven to have positive effects
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