Metabolic biomarkers related to energy metabolism in Saudi autistic children.

OBJECTIVES: Energy metabolism is usually manipulated in many neurodegenerative diseases. Autism is considered a definable systemic disorder resulting in a number of diverse factors that may affect the brain development and functions both pre and post natal. The increased prevalence of autism will have enormous future public implications and has stimulated intense research into potential etiologic factors. This study aims to establish a connection between autism and the deterioration accompanied it, especially in the brain cognitive areas through a postulation of energy manipulation.

MATERIALS AND METHODS: The biochemical changes in activities of enzymes and pathways that participate in the production of ATP as the most important high-energy compound needed by the human brain were measured in Saudi autistic children. Na(+)/K(+)ATPase, ectonucleotidases (NTPDases) (ADPase and ATPase) and CREATINE KINASE (CK), were assessed in plasma of 30 Saudi autistic patients and compared to 30 age-matching control samples. In addition, adenosine mono, di and trinucleotides (ATP, ADP, and AMP) were measured calorimetrically in the red blood cells of both groups and the adenylate energy charge (AEC) was calculated. Moreover, lactate concentration in plasma of both groups was monitored.

RESULTS: The obtained data recorded 148.77% and 72.35% higher activities of Na(+)/K(+)ATPase and CREATINE KINASE respectively in autistic patients which prove the impairment of energy metabolism in these children compared to age and sex matching healthy controls. While ADPase was significantly higher in autistic patients, ATPase were non-significantly elevated compared to control. In spite of the significant increase of Na(+)/K(+)ATPase activity in autistic patients, there was no significant difference in the levels of ATP, ADP, and AMP in both groups and the calculated AEC values were 0.814+/-0.094 and 0.806+/-0.081 for autistic and control groups respectively. The unchanged AEC value in autistic patients was easily correlated with the induced activity of CK and ADPase as two enzymes playing a critical role in the stabilization of AEC. Lactate as an important energy metabolite for the brain was significantly higher in autistic patients compared to control showing about 40% increase.

CONCLUSION: The present study confirmed the impairment of energy metabolism in Saudi autistic patients which could be correlated to the oxidative stress previously recorded in the same investigated samples. The identification of biochemical markers related to autism would be advantageous for earlier clinical diagnosis and interventio

Stereospecificity, substrate, and inhibitory properties of nucleoside diphosphate analogs for creatine and pyruvate kinases

Antiviral -P-borano substituted NTPs are promising chain terminators targeting HIV reverse transcriptase (RT). Activation of antiviral nucleoside diphosphates (NDPs) to NTPs may be carried out by pyruvate kinase (PK) and creatine kinase (CK). Herein, are presented the effects of nucleobase, ribose, and -phosphate substitutions on substrate specificities of CK and PK. Both enzymes showed two binding modes and negative cooperativity with respect to substrate binding. The stereospecificity and inhibition of ADP phosphorylation by -P-borano substituted NDP (NDPB) stereoisomers were also investigated. The Sp-ADPB isomer was a 70-fold better substrate for CK than the Rp isomer, whereas PK preferred the Rp isomer of NDPBs. For CK, the Sp-ADPB isomer was a competitive inhibitor; for PK, the Rp-ADPB isomer was a poor competitive inhibitor and the Sp-ADPB isomer was a poor non-competitive inhibitor. Taken together, these data suggest that, although the Rp-NDPB isomer would be minimally phosphorylated by CK or PK, it should not inhibit either enzyme.



ARTICLE

Creatine Kinase–Mediated ATP Supply Fuels Actin-Based Events in Phagocytosis

Phagocytosis requires locally coordinated cytoskeletal rearrangements driven by actin polymerization and myosin motor activity. How this actomyosin dynamics is dependent upon systems that provide access to ATP at phagosome microdomains has not been determined. We analyzed the role of brain-type creatine kinase (CK-B), an enzyme involved in high-energy phosphoryl transfer. We demonstrate that endogenous creatine kinase (CK-B), in macrophages is mobilized from the cytosolic pool and coaccumulates with F-actin at nascent phagosomes. Live cell imaging with XFP-tagged CK-B and β-actin revealed the transient and specific nature of this partitioning process. Overexpression of a catalytic dead CK-B or CK-specific cyclocreatine inhibition caused a significant reduction of actin accumulation in the phagocytic cup area, and reduced complement receptor–mediated, but not Fc-γR–mediated, ingestion capacity of macrophages. Finally, we found that inhibition of CK-B affected phagocytosis already at the stage of particle adhesion, most likely via effects on actin polymerization behavior. We propose that CK-B activity in macrophages contributes to complement-induced F-actin assembly events in early phagocytosis by providing local ATP supply.

Comparison of MB Fraction of Creatine Kinase Mass and Troponin I Serum Levels With Necropsy Findings in Acute Myocardial Infarction

Serum levels of troponin and heart-related fraction of creatine kinase (CK-MB) mass are used as diagnostic and prognostic criteria in myocardial infarction , but the relation between those levels and the necropsy-determined size of necrosis has not been tested in human beings.

In this retrospective study, 1-cm-thick transverse sections of the ventricles were cut from the base to the apex in the necropsy hearts of 27 patients aged 47 to 86 years (mean 66, median 69; 19 men). Total and necrotic areas were measured using a computer-linked image analysis system. The weights of the necrotic areas were also calculated.

The correlations of the areas and weights of necrotic myocardium with the highest serum values of CK-MB mass and troponin I, which had been quantified during life by chemiluminescence immunoassays, were verified by Pearson's test; results were considered significant at p <=0.05.

Significant correlations were detected between Creatine Kinase isoenzyme mb (CK-MB) mass peak and infarct size (r = 0.63, p <0.01) and weight (r = 0.69, p <0.01) and between CK-MB mass and highest troponin level (r = 0.73, p <0.01); however, the correlations between highest troponin level and myocardial infarct size (r = 0.31, p = 0.11) and weight (r = 0.35, p = 0.07) were small and nonsignificant.

In conclusion, despite the well-established role of serum levels of troponin as a diagnostic tool for myocardial infarction, their highest values showed poor correlations with the extent of infarct. In contrast, the highest serum level of CK-MB mass was well correlated with myocardial infarct size.


Costa TN, Cassaro Strunz CM, Nicolau JC, Gutierrez PS.
Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Am J Cardiol. 2008 Feb 1;101(3):311-4.

New physiological model of serum creatine phosphokinase activity in acute myocardial infarction

In this report, we introduce a new physiological model of the serum creatine phosphokinase (CPK) activity change, that is useful for estimating the total CPK release accurately even with reduced blood sampling frequency. The physiological model was applied to the serum creatine kinase CPK activity change of patients who suffered acute myocardial infarction (AMI), and the model showed good agreement with the serum CPK activity. In addition, the calculated value of total CPK release agreed well with that calculated using the conventional technique.

Faculty of Health Sciences, Okayama University Graduate School, 2-5-1 Shikata, Okayama-shi, Okayama, JAPAN,Conf Proc IEEE Eng Med Biol Soc. 2007;1:912-5,Kitawaki T, Oka H, Kusachi S, Himeno R.

Creatine Kinase levels

Abstract: Creatine Kinase levels in unmedicated bipolar patients
Various reports have described increased serum creatine kinase (CK) activity in the majority of hospitalized acutely disturbed schizophrenics and patients with affective psychoses. We investigated creatine kinase serum levels of 52 unmedicated bipolar inpatients, in manic versus depressive states.

Additional 17 patients were evaluated in both states. Hamilton Rating Scale for Depression and Young Mania Rating Scale were used and blood samples were obtained from new admitted patients. Higher creatine kinase level was found in the manic patients compared with the depressed ones.

Likewise, the creatine kinase level was higher in the manic phase than in the depressive one, when tested within the same patient.

Our results suggest that the clinical differences between mania and depression states are supported by contrasting levels of creatine kinase CK . The lack of correlations between creatine kinase level and motor items suggest that creatine kinase CK level in mania versus depression could emphasize the “thinking speed” and not the motor one.

European Neuropsychopharmacology
Volume 17, Issue 12, December 2007, Pages 763-767
i:10.1016/j.euroneuro.2007.04.007
Tel Aviv University, Tel Aviv, Israel

CREATINE KINASE LATEST RESEARCH

Incidence of Increased Creatine Kinase and its Effect on Kidney Function in Hand Assisted Laparoscopic Kidney Donors and Their Recipients. Serum creatine kinase was prospectively measured in 74 consecutive patients who underwent hand assisted laparoscopic donor nephrectomy. Creatine kinase elevation occurs in a small but significant number of patients. Operative time was an independent risk factor for increased creatine kinase . Although creatine kinase had no significant effect on short-term creatinine, there was an increase in the percent change in donor creatinine. Finally, the long-term significance of increased creatine kinase without clinical symptoms is unknown. source: The Journal of Urology
Volume 178, Issue 4, October 2007, Pages 1391-1395

Creatine kinase (CK) isoenzymes are essential for storing, buffering and intracellular transport of “energy-rich” phosphate compounds in tissues with fluctuating high energy demand such as muscle, brain and other tissues and cells where Creatine Kinase CK is expressed. Using dividing HeLa cells, we report here for the first time that GM130 and Creatine Kinase BB isoenzyme BB-CK co-localize specifically in a transient fashion during early prophase of mitosis, when GM130 plays an important role in Golgi fragmentation that starts also at early prophase. These data may shed new light on CK BB Isoenzyme BB-CK function for energy provision for Golgi-fragmentation that is initiated by cell signalling cascades in the early phases of mitosis. source:
Institute of Cell Biology HPM D24, ETH ZURICH, Schafmattstr. 18, Zurich, 8093, Switzerland