Psychiatry related information on Ckmt1

• We measured contractile function, oxygen consumption, and the mean response time of oxygen consumption to a step increase in heart rate [i.e., mitochondrial response time (t(mito))] in isolated Langendorff-perfused hearts from wild-type (n = 6), M/MtCK(-/-) (n = 6), and AK(-/-) (n = 4) mice [1].

High impact information on Ckmt1

• Hearts from wild-type, MCK-/-, and M/MtCK-/- mice had comparable baseline function and responded to 10 minutes of increased heart rate and perfusate Ca2+ with similar increases in rate-pressure product (48+/-5%, 42+/-6%, and 51+/-6%, respectively) [2].
• In contrast to what has been reported in skeletal muscle, M/MtCK-/- hearts were able to hydrolyze and resynthesize phosphocreatine [2].
• The free energy released from ATP hydrolysis decreased by 3.6 kJ/mol in M/MtCK-/- hearts during increased cardiac work but only slightly in wild-type (1.7 kJ/mol) and MCK-/- (1.5 kJ/mol) hearts [2].
• In hearts lacking both M- and Mt-CK, the rate of ATP synthesis from PCr was only 9% of the rate of ATP synthesis from oxidative phosphorylation demonstrating a lack of any high energy phosphate shuttle [3].
• The chicken Mia-CK gene spans about 7.6 kilobases and contains 9 exons [4].

Biological context of Ckmt1

• Finally, combined loss of M- and Mt-CK (but not loss of only M-CK) prevented the amount of free energy released from ATP hydrolysis from increasing when pyruvate was provided as a substrate for oxidative phosphorylation [3].
• Previously, we reported that mice deficient for BCK or UbCKmit each showed a surprisingly mild phenotype, probably due to reciprocal functional compensation by the remaining creatine kinase [5].
• We have introduced a single knock-out mutation in the mitochondrial creatine kinase gene (ScCKmit) in the mouse germ line via targeted mutagenesis in mouse embryonic stem (ES) cells [6].
• UbCKmit-deficient cells, obtained by consecutive rounds of gene targeting using homologous recombination and drug selection-driven gene conversion events, show no obvious growth disadvantage or abnormal differentiation potential [7].
• These findings demonstrate coordinate regulation of MtCK and cytosolic CK gene expression and support the phosphocreatine shuttle hypothesis [8].

Anatomical context of Ckmt1

• The importance of mitochondrial creatine kinase (mi-CK) in oxidative muscle was tested by studying the functional properties of in situ mitochondria in saponin-skinned muscle fibres from sarcomeric mi-CK-deficient (mutant) mice [9].
• The cytosolic brain-type creatine kinase (BCK) isoform and the mitochondrial ubiquitous creatine kinase (UbCKmit) isoform are both important for the maintenance and distribution of cellular energy in neurons and astrocytes [5].
• Motility patterns of isolated spermatozoa were analyzed and found not to be impaired by absence of UbCKmit [10].
• Using targeted mutagenesis via homologous recombination in embryonic stem cells, we have generated mice that are deficient in UbCKmit subunits [10].
• In mouse, protein subunits constituting the ubiquitous mitochondrial CK (UbCKmit) and cytosolic B-CK isoforms are co-expressed in various cells and tissues with high and fluctuating energy demands such as brain, retina, smooth muscle, uterus, placenta and spermatozoa [10].

Associations of Ckmt1 with chemical compounds

• There was no change in the K(m) in oxidative fibres from mutant mice (258 +/- 27 and 399 +/- 66 microM, respectively) compared with control, though surprisingly, it was also significantly decreased in the presence of creatine (144 +/- 8 and 150 +/- 27 microM, respectively) despite the absence of mi-CK [9].
• Residues 1-14 of human placental MtCK cDNA-derived NH2-terminal sequence differ from the human heart MtCK protein sequence, suggesting that tissue-specific MtCK mRNAs are derived from multiple MtCK genes [8].
• We predict that the remaining functional intactness of the cytosolic B-CK reaction and perhaps the compensatory role of other phosphoryl transfer systems are sufficient to sustain the energy requirements for basic sensory, motor and physiological activities in UbCKmit-/- mice [11].
• We have blocked creatine kinase (CK) mediated phosphocreatine (PCr) <==> ATP transphosphorylation in mitochondria and cytosol of skeletal muscle by knocking out the genes for the mitochondrial (ScCKmit) and the cytosolic (M-CK) CK isoforms in mice [12].

Other interactions of Ckmt1

• This study assessed the metabolic and anatomical consequences of partial or complete depletion of this system in transgenic mice without cytosolic B-CK (B-CK-/-), mitochondrial ubiquitous CK (UbCKmit-/-), or both isoenzymes (CK -/-), using non-invasive quantitative magnetic resonance (MR) imaging and spectroscopy [13].

Analytical, diagnostic and therapeutic context of Ckmt1

• We have studied the mechanisms that regulate the remodeling of the glycolytic, mitochondrial and structural network of muscles of creatine kinase M (M-CK)/sarcomeric mitochondrial creatine kinase (ScCKmit) knockout mice by comparison of wild-type and mutant mRNA profiles on cDNA arrays [14].

References