phosphorus-radioisotopes and phosphocreatinine

Down's syndrome (DS) is a developmental disorder associated with intellectual disability (ID). We have previously shown that people with DS engage in very low levels of exercise compared to people with ID not due to DS. Many aspects of the DS phenotype, such as dementia, low activity levels and poor muscle tone, are shared with disorders of mitochondrial origin, and mitochondrial dysfunction has been demonstrated in cultured DS tissue. We undertook a phosphorus magnetic resonance spectroscopy ((31)P-MRS) study in the quadriceps muscle of 14 people with DS and 11 non-DS ID controls to investigate the post-exercise resynthesis kinetics of phosphocreatine (PCr), which relies on mitochondrial respiratory function and yields a measure of muscle mitochondrial function in vivo. We found that the PCr recovery rate constant was significantly decreased in adults with DS compared to non-DS ID controls (1.7 ± 0.1 min(-1) vs 2.1 ± 0.1 min(-1) respectively) who were matched for physical activity levels, indicating that muscle mitochondrial function in vivo is impaired in DS. This is the first study to investigate mitochondrial function in vivo in DS using (31)P-MRS. Our study is consistent with previous in vitro studies, supporting a theory of a global mitochondrial defect in DS.

Topics: Adult; Case-Control Studies; Down Syndrome; Energy Metabolism; Exercise; Female; Humans; Intellectual Disability; Kinetics; Magnetic Resonance Spectroscopy; Male; Mitochondria, Muscle; Muscle, Skeletal; Phosphocreatine; Phosphorus Radioisotopes

Assessment of left ventricular metabolism and function is important in patients on maintenance dialysis because congestive heart failure occurs quite frequently and has a poor prognosis. The purpose of this study was to evaluate the changes of myocardial high energy metabolism in dialysis patients by using phosphorus-31 (31P) magnetic resonance (MR) spectroscopy.. Phosphorus-31 spectra were obtained from anteroseptal wall of the heart in six normal subjects (mean age, 24 +/- 1 years) and 14 dialysis patients (mean age, 52 +/- 11 years), using a 1.5-tesla clinical MR system. Four patients had previous history of heart failure. Echocardiography was performed in all patients to evaluate left ventricular (LV) hypertrophy and LV function.. The averaged ratio of phosphocreatine (PCr)/beta-adenosine triphosphate (beta-ATP) in dialysis patients (1.15 +/- 0.25 mean +/- standard deviation), was significantly lower than that in healthy subjects (1.63 +/- 0.21; P < 0.01). There was no significant difference in PCr/beta-ATP ratios between the non-LV hypertrophy group (1.21 +/- 0.24; n = 7) and the LV hypertrophy group (1.09 +/- 0.24; n = 7). The averaged PCr/beta-ATP ratio in four patients with history of heart failure (0.96 +/- 0.18) was significantly lower than that of the 10 patients without history of heart failure (1.22 +/- 0.23; P < 0.05).. These results indicate that patients on maintenance dialysis have decreased PCr/beta-ATP ratio and 31P MR spectroscopy can provide noninvasive assessment of altered high energy phosphate metabolism.

Topics: Adenosine Triphosphate; Adult; Aged; Female; Heart Failure; Heart Ventricles; Humans; Kidney Failure, Chronic; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardium; Phosphocreatine; Phosphorus; Phosphorus Radioisotopes; Renal Dialysis

The effects of local irradiation and intraperitoneal injection of cisplatinum (CDDP) and VP-16 were examined in the sequential 31P magnetic resonance spectroscopy (MRS) in testicular cancer (TC-1) and bladder tumor (BT-8) of human origin, serially transplanted in nude mice. In the early phase of tumor growth, high-energy phosphate metabolites such as phosphocreatinine (PCr), adenosine triphosphate (ATP) and phosphomonoester (PME) were detected in both grafted tumors. However, the relative value of inorganic phosphate (Pi) to PCr increased with the growth of the tumor. Irradiation had the most pronounced effect to inhibit growth, followed by CDDP in both strains. However, growth inhibition was not observed in the VP-16 group. The effect of irradiation on the tumor histology was severely expressed in the nucleus and cytoplasm on the 4th to 7th day. The high PCr/Pi ratio during 2 to 14 days after irradiation suggested reoxygenation in the tumors with a high hypoxic cell fraction. In the CDDP and VP-16 groups, without histological change, the changes of PCr and Pi were milder than that in the irradiation group. Thus the spectroscopic analysis is presumably expected to give us an earlier and more accurate information on the tumor than the conventional parameters.

Topics: Adenosine Triphosphate; Animals; Antineoplastic Combined Chemotherapy Protocols; Humans; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Phosphocreatine; Phosphorus Radioisotopes; Testicular Neoplasms; Urinary Bladder Neoplasms

Phosphocreatine (PCr) was found to alter the phosphorylation state of two proteins of apparent molecular masses 18 and 29 kDa in dialysed cell-free extracts of rat skeletal muscle in the presence of [gamma-32P]ATP. The 29 kDa protein was identified as phosphoglycerate mutase (PGM), phosphorylated at the active-site histidine residue by 2,3-bisphosphoglycerate (2,3-biPG). 2,3-biPG labelling from [gamma-32P]ATP occurred through the concerted action of phosphoglycerate kinase and 2,3-bisphosphoglycerate mutase. PCr-dependent labelling, which required creatine kinase, resulted from a shift in the phosphoglycerate kinase equilibrium towards 1,3-bisphosphoglycerate (1,3-biPG) synthesis, ultimately resulting in an increase in available [2-32P]2,3-biPG. The maximal catalytic activity of PGM was unaffected by PCr. The 18 kDa protein was transiently phosphorylated at a histidine residue, probably by 1,3-biPG. No proteins of this monomeric molecular mass are known to bind 1,3-biPG, suggesting that the 18 kDa protein is an undescribed phosphoenzyme intermediate. Previous observations of 2- and 3-phosphoglycerate-dependent protein phosphorylation in cytosolic extracts [Ueda & Plagens (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 1229-1233; Pek, Usami, Bilir, Fischer-Bovenkerk & Ueda (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 4294-4298], attributed to the action of novel kinases, are likely to represent phosphoenzyme intermediates labelled by bisphosphorylated metabolites in a similar manner.

Topics: 2,3-Diphosphoglycerate; Adenosine Triphosphate; Animals; Binding Sites; Bisphosphoglycerate Mutase; Creatine Kinase; Cytosol; Diphosphoglyceric Acids; Histidine; Kinetics; Male; Molecular Weight; Muscle Proteins; Muscles; Phosphocreatine; Phosphoglycerate Kinase; Phosphoglycerate Mutase; Phosphorus Radioisotopes; Phosphorylation; Rats; Rats, Inbred Strains