Johannes H. G. M. van Beek

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The representation of biochemical knowledge in terms of fluxes (transformation rates) in a metabolic network is often a crucial step in the development of new drugs and efficient bioreactors. Mass spectroscopy (MS) and nuclear magnetic resonance spectroscopy (NMRS) in combination with C labeled substrates are experimental techniques resulting in data that(More)
The literature is reviewed on methods to assess heterogeneity of blood flow, substrate uptake and oxidative end energy metabolism in the normal heart, and their interrelations. Even though the factors controlling matching on the regional level remain largely obscure, the evidence that heterogeneous blood flow partially correlates to indicators of metabolism(More)
The cells of the human body each contain thousands of molecular species, the dynamic interactions of which constitute the biomolecular system underlying cellular function. Many thousands of expressed genes, proteins, and metabolites can be measured simultaneously in a tissue or blood sample, making a scan of most biomolecules possible. This wealth of(More)
MOTIVATION Quantitative determination of metabolic fluxes in single tissue biopsies is difficult. We report a novel analysis approach and software package for in vivo flux quantification using stable isotope labeling. RESULTS We developed a protocol based on brief, timed infusion of (13)C isotope-enriched substrates for the tricarboxylic acid (TCA) cycle(More)
In this study the function of the two isoforms of creatine kinase (CK; EC 2.7.3.2) in myocardium is investigated. The 'phosphocreatine shuttle' hypothesis states that mitochondrial and cytosolic CK plays a pivotal role in the transport of high-energy phosphate (HEP) groups from mitochondria to myofibrils in contracting muscle. Temporal buffering of changes(More)
Using a heterologous probe containing a fragment of the L25-gene from Saccharomyces carlsbergensis we have isolated a DNA-fragment of Candida utilis carrying the gene encoding ribosomal protein L25. This gene is present in a single copy on the C. utilis genome, though as two distinguishable alleles. Both alleles have been isolated and sequenced including(More)
The response of mitochondrial oxygen consumption to ADP in saponin-skinned cardiac fibre bundles has an apparent K m an order of magnitude higher than that in isolated mitochondria. Here we report that incubating skinned cardiac fibre bundles from wild-type mice or double-knockout mice lacking both cytosolic and mitochondrial creatine kinase (CK) with CK(More)
The aerobic energy metabolism of cardiac muscle cells is of major importance for the contractile function of the heart. Because energy metabolism is very heterogeneously distributed in heart tissue, especially during coronary disease, a method to quantify metabolic fluxes in small tissue samples is desirable. Taking tissue biopsies after infusion of(More)
We have designed a method to encode properties related to the electron densities of molecules (calculated (1)H and (13)C NMR shifts and atomic partial charges) in molecular fingerprints (EDprints). EDprints was evaluated in terms of their retrospective virtual screening accuracy against the Directory of Useful Decoys (DUD) and compared to the established(More)
To investigate the dynamic control of cardiac ATP synthesis, we simultaneously determined the time course of mitochondrial oxygen consumption with the time course of changes in high-energy phosphates following steps in cardiac energy demand. Isolated isovolumically contracting rabbit hearts were perfused with Tyrode's solution at 28°C (n=7) or at 37°C(More)