Metabolite channeling: A phosphorylcreatine shuttle to mediate high energy phosphate transport between sperm mitochondrion and tail

Cell ◽  
1985 ◽  
Vol 41 (1) ◽  
pp. 325-334 ◽  
Author(s):  
Robert M. Tombes ◽  
Bennett M. Shapiro
Keyword(s):  
Phosphate Transport ◽  
High Energy ◽  
High Energy Phosphate ◽  
Metabolite Channeling

Robust modelling, measurement and analysis of human and animal metabolic systems

2009 ◽  
Vol 367 (1895) ◽  
pp. 1971-1992 ◽  
Author(s):  
Johannes H.G.M. van Beek ◽  
Anne-Christin Hauschild ◽  
Hannes Hettling ◽  
Thomas W. Binsl
Keyword(s):  
Metabolic Flux ◽  
Phosphate Transport ◽  
High Energy ◽  
High Energy Phosphate ◽  
Stable Isotope Labelling ◽  
Metabolic System ◽  
Ensemble Simulations ◽  
Metabolic Systems ◽  
Animal Metabolism

Modelling human and animal metabolism is impeded by the lack of accurate quantitative parameters and the large number of biochemical reactions. This problem may be tackled by: (i) study of modules of the network independently; (ii) ensemble simulations to explore many plausible parameter combinations; (iii) analysis of ‘sloppy’ parameter behaviour, revealing interdependent parameter combinations with little influence; (iv) multiscale analysis that combines molecular and whole network data; and (v) measuring metabolic flux (rate of flow) in vivo via stable isotope labelling. For the latter method, carbon transition networks were modelled with systems of ordinary differential equations, but we show that coloured Petri nets provide a more intuitive graphical approach. Analysis of parameter sensitivities shows that only a few parameter combinations have a large effect on predictions. Model analysis of high-energy phosphate transport indicates that membrane permeability, inaccurately known at the organellar level, can be well determined from whole-organ responses. Ensemble simulations that take into account the imprecision of measured molecular parameters contradict the popular hypothesis that high-energy phosphate transport in heart muscle is mostly by phosphocreatine. Combining modular, multiscale, ensemble and sloppy modelling approaches with in vivo flux measurements may prove indispensable for the modelling of the large human metabolic system.

scholarly journals High-energy phosphate transfer in human muscle: diffusion of phosphocreatine

2011 ◽  
Vol 301 (1) ◽  
pp. C234-C241 ◽  
Author(s):  
Refaat E. Gabr ◽  
AbdEl-Monem M. El-Sharkawy ◽  
Michael Schär ◽  
Robert G. Weiss ◽  
Paul A. Bottomley
Keyword(s):  
Diffusion Coefficient ◽  
Energy Transport ◽  
Phosphate Transport ◽  
High Energy ◽  
Human Muscle ◽  
Energy Utilization ◽  
Resonance Spectroscopy ◽  
High Energy Phosphate ◽  
Muscle Energetics

The creatine kinase (CK) reaction is central to muscle energetics, buffering ATP levels during periods of intense activity via consumption of phosphocreatine (PCr). PCr is believed to serve as a spatial shuttle of high-energy phosphate between sites of energy production in the mitochondria and sites of energy utilization in the myofibrils via diffusion. Knowledge of the diffusion coefficient of PCr ( DPCr) is thus critical for modeling and understanding energy transport in the myocyte, but DPCr has not been measured in humans. Using localized phosphorus magnetic resonance spectroscopy, we measured DPCr in the calf muscle of 11 adults as a function of direction and diffusion time. The results show that the diffusion of PCr is anisotropic, with significantly higher diffusion along the muscle fibers, and that the diffusion of PCr is restricted to a ∼28-μm pathlength assuming a cylindrical model, with an unbounded diffusion coefficient of ∼0.69 × 10−3 mm2/s. This distance is comparable in size to the myofiber radius. On the basis of prior measures of CK reaction kinetics in human muscle, the expected diffusion distance of PCr during its half-life in the CK reaction is ∼66 μm. This distance is much greater than the average distances between mitochondria and myofibrils. Thus these first measurements of PCr diffusion in human muscle in vivo support the view that PCr diffusion is not a factor limiting high-energy phosphate transport between the mitochondria and the myofibrils in healthy resting myocytes.

scholarly journals Energy Metabolism of Human Leukemic Lymphocytes and Granulocytes

Blood ◽  
1967 ◽  
Vol 30 (2) ◽  
pp. 151-167 ◽  
Author(s):  
JOHN LASZLO ◽  
Clarence Ellis
Keyword(s):  
Energy Metabolism ◽  
Chronic Lymphocytic Leukemia ◽  
Glucose Concentration ◽  
Acute Lymphocytic Leukemia ◽  
Aerobic Glycolysis ◽  
High Energy ◽  
Lymphocytic Leukemia ◽  
Anaerobic Conditions ◽  
High Energy Phosphate

Abstract 1. Leukocytes taken from patients having acute lymphocytic leukemia and chronic lymphocytic leukemia are characterized by high respiratory rates and low to absent aerobic glycolysis. Leukemic granulocytes have low respiratory rates and high aerobic glycolysis. 2. Lymphocytes and granulocytes have the capacity for high glycolytic rates under anaerobic conditions. 3. Lymphocyte respiration is independent of glucose concentration in contrast to granulocyte respiration. 4. High energy phosphate levels of lymphocytes and granulocytes are unchanged if these cells are incubated aerobically, either with or without glucose, or anaerobically in the presence of glucose. 5. Aerobic glycolysis can be induced in lymphocytes by the addition of foreign plasma. Foreign plasma may also alter granulocyte metabolism.

Responses of beta-adrenoceptor in rat soleus to phosphorus compound levels and/or unloading

1994 ◽  
Vol 266 (5) ◽  
pp. C1257-C1262 ◽  
Author(s):  
Y. Ohira ◽  
K. Saito ◽  
T. Wakatsuki ◽  
W. Yasui ◽  
T. Suetsugu ◽  
...  
Keyword(s):  
Contractile Activity ◽  
Creatine Supplementation ◽  
High Energy ◽  
Hindlimb Suspension ◽  
Phosphorus Compounds ◽  
High Energy Phosphates ◽  
High Energy Phosphate ◽  
Gravitational Unloading ◽  
Beta Adrenoceptor ◽  
Muscle Contractile

Responses of beta-adrenoceptor (beta-AR) in rat soleus to gravitational unloading and/or changes in the levels of phosphorus compounds by feeding either creatine or its analogue beta-guanidinopropionic acid (beta-GPA) were studied. A decrease in the density of beta-AR (about -35%) was induced by 10 days of hindlimb suspension, but the affinity of the receptor was unaffected. Suspension unloading tended to increase the levels of adenosine triphosphate and phosphocreatine and decrease inorganic phosphate. Even without unloading, the beta-AR density decreased after an oral creatine supplementation (about -20%), which also tended to elevate the high-energy phosphate levels in muscle. However, an elevation of beta-AR density was induced (about +36%) after chronic depletion of high-energy phosphates by feeding beta-GPA (about +125%). Data suggest that the density of beta-AR in muscle is elevated if the high-energy phosphate contents are chronically decreased and vice versa. However, it may not be directly related to the degree of muscle contractile activity.

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