Scheme of energy metabolism in heart and skeletal muscle cells. Two sources of ATP re-synthesis, mitochondrial oxidative phosphorylation and glycolysis, are interconnected with sites of ATP hydrolysis via the phosphocreatine/creatine kinase (PCr/CK) shuttle. GLUT4 glucose transporter, FATP1 fatty acid transport protein, β-FAO beta-oxidation of fatty acids, PHD pyruvate dehydrogenase, PTP permeability transition pore, VDAC voltage-dependent anion channel, TpC troponin C, AP action potential. The isoforms of the creatine kinase (CK) present in different subcellular compartments are coupled with both ATP producing (mitochondrial and glycolytic) and ATP consuming (contraction, ions pumping) processes. In muscle cells sarcomeric mitochondrial CK (MtCK) functionally coupled to ATP synthase via adenine nucleotide translocase (ANT) and cytosolic isoforms of CK (MMCK and MBCK) coupled to glycolytic enzymes (phosphoglycerate kinase (PGK) and pyruvate kinase (PK) catalyse forward reaction of phosphocreatine (PCr) synthesis from mitochondrial or glycolytic ATP and creatine). The MMCK functionally coupled to myosin ATPases, sarcoplasmic reticulum ATPases or ions-pumping-ATPases catalyse reverse reaction of ATP regeneration from PCr and locally produced ADP. The prevalence of one of the ways of PCr production is tissue specific. In cardiac and oxidative muscle cells PCr used for muscle contraction is produced mainly from mitochondrial ATP, while in fast twitch glycolytic muscle it is produced from ATP supplied by glycolysis
The central role of Cr, PCr and CK (Cr/PCr/CK) system in cardiac
cells is shown in Fig. 1.
2001) (Fig. 1).
Rapid decline in heart contractile function in hypoxia and ischemia
are most likely to be related to changes in compartmentalized
energy transfer systems, leading to decreased regeneration of ATP
in functionally important cellular compartments, as shown in
These microdomains are localised in myofibrils, near the sarcolemma
and the membrane of sarcoplasmic reticulum in muscle cells and near
cellular membrane in brain cells (see Fig. 1).
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