Endogenous cardiotonic steroids

Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure . D M Mancini, E Coyle, A Coggan, J Beltz, N Ferraro, S Montain, J R Wilson. Circulation. November 1989;80(5):1338-1346. Quote: Patients with heart failure frequently exhibit abnormal skeletal muscle metabolic responses to exercise, as assessed with 31P NMR. To investigate whether these metabolic abnormalities are due to intrinsic skeletal muscle changes, we performed gastrocnemius muscle biopsies on 22 patients with heart failure and on eight normal subjects. Biopsies were analyzed for fiber type and area, capillarity, citrate synthase, phospho-fructokinase, lactate dehydrogenase, and beta-hydroxyacyl CoA dehydrogenase activity. All patients with heart failure also underwent 31P NMR studies of their calf muscle during plantarflexion at three workloads. Muscle pH responses and the relation of the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) to systemic VO2 were then evaluated. Compared with normal subjects, patients with heart failure exhibited a shift in fiber distribution with increased percentage of the fast twitch, glycolytic, easily fatigable type IIb fibers, atrophy of type IIa and type IIb fibers, and decreased activity of beta-hydroxyacyl CoA dehydrogenase... Type IIb fibers represent fibers that are fast twitch, have a low aerobic potential, and are easily fatigued... No significant linear correlation could be identified between the slope of the Pi/PCr to VO2 relation and muscle histochemistry or enzyme activities. Similarly, no linear relation was found between intracellular pH at peak exercise and any muscle variable. These data suggest that patients with heart failure develop intrinsic skeletal muscle changes but that these intrinsic muscle changes do not contribute significantly to the abnormal skeletal muscle 31P NMR metabolic responses observed in such patients.

There are numerous classes of protein that span the membrane of cells, be it the plasma membrane or intracellular organellar membranes. The transmembrane proteins include the various ion channels, other types of channel proteins, transporter proteins, growth factor receptors, and cell adhesion molecules. All transmembrane proteins, regardless of function, are classified dependent upon their structure. There are four main classifications for transmembrane proteins, type I, II, III, and IV. Types I, II, and III are all characterized by passing through the membrane once, referred to as single-pass transmembrane proteins. Type IV transmembrane proteins pass through the membrane several times and, therefore, they are all referred to as multiple-pass transmembrane proteins. Type I transmembrane proteins are anchored to the membrane via a sequence of hydrophobic amino acids referred to as the stop-transfer sequence and this class all have the C-terminus of the protein inside the cell and the N-terminus outside. A typical example of a type I transmembrane protein is the LDL receptor . Type II transmembrane proteins are anchored to the membrane via a signal-anchor sequence and have the C-terminus outside the cell and the N-terminus inside. An example of a type II transmembrane protein is the transferrin receptor . Type III transmembrane proteins do not have a signal sequence and the N-terminus of the protein is outside the cell. An example of a type III transmembrane protein would be any member of the cytochrome P450 family of xenobiotic metabolizing enzymes found in the liver. Type IV transmembrane proteins are typified by the G-protein coupled receptor (GPCR) superfamily of receptor proteins that span the membrane seven times. This class of receptor is often referred to as the serpentine receptor family because of the multiple membrane spans. Another example of a type IV transmembrane protein is the α-subunit of a typical Na + ,K + -ATPase (see below). Type IV transmembrane proteins are divided into type IV-A and type IV-B where the IV-A members have the N-terminus inside the cell and the C-terminus outside and the IV-B members are oriented in the opposite direction. The Na + ,K + -ATPase α-subunit proteins are type IV-A multi-pass transmembrane proteins, whereas, all GPCRs are members of the type IV-B family.

Endogenous cardiotonic steroids

endogenous cardiotonic steroids


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