pyrophosphate and phosphorylethanolamine

Development of biological and clinical uses of in vivo 31P magnetic resonance spectroscopy has been hampered by poor anatomic localization of spectra and poor resolution of overlapping signals within phosphomonoester and phosphodiester regions of the spectrum. We applied 1H-decoupling and nuclear Overhauser enhancement to improve resolution of 31P magnetic resonance spectra accurately localized to 21 non-Hodgkin's lymphomas (NHL) by using three-dimensional chemical shift imaging. All 21 spectra had large phosphomonoester signals (26% of total phosphorus) that contained high amounts of phosphoethanolamine relative to phosphocholine. There were no signals from glycerophosphoethanolamine or glycerophosphocholine but only a broad signal from membrane phospholipids in the phosphodiester region (20% of phosphorus). Prominent nucleoside triphosphates (47% of phosphorus) and low inorganic phosphate (7% of phosphorus) indicate well-perfused tissue with viable cells. Mean intracellular pH was 7.23. These characteristics were similar in all grades and stages of NHL. By analogy with recently reported studies in cell lines in vitro, we hypothesize that the pattern of phospholipid metabolites observed in NHL in vivo is partly a manifestation of sustained activation of phospholipase C or D. The techniques we implemented permitted us to obtain more information about in vivo metabolism of NHL than has heretofore been available. This information is important for the establishment of appropriate experimental models and provides a basis from which to examine potential clinical uses of 31P magnetic resonance spectroscopy.

Topics: 2,3-Diphosphoglycerate; Adult; Aged; Diphosphates; Diphosphoglyceric Acids; Esters; Ethanolamines; Female; Humans; Lymphoma, Non-Hodgkin; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphatidylethanolamines; Phosphocreatine; Phosphorylcholine

Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.

Topics: Alkaline Phosphatase; Diphosphates; Ethanolamines; Female; Heterozygote; Humans; Hypophosphatasia; Isoenzymes; Placenta; Pregnancy; Prospective Studies; Pyridoxal Phosphate; Substrate Specificity

Hypophosphatasia is an inherited disease in which a deficiency of the bone/liver/kidney or tissue nonspecific isoenzyme of alkaline phosphatase (AP; EC 3.1.3.1) occurs. All forms of the disease are characterized clinically by defective mineralization. Several biochemical abnormalities are associated with the deficiency of AP activity, e.g., increased urinary excretion of inorganic pyrophosphate (PPi) and phosphoethanolamine (PEA). Measurement of these analytes in kindreds of patients with hypophosphatasia may be useful in identifying carriers, and in understanding the inheritance of the disease. We studied biochemically 22 members of the kindred of a 24-year-old woman with hypophosphatasia. We measured activity of AP in serum and leukocytes, and the urinary excretion of PPi and PEA. Within this kindred, urinary excretion of PPi appeared to indicate carrier status, and among the clinically normal adults, values for this analyte were inversely correlated with the activity of AP in serum. These results suggest that urinary excretion of PPi is sensitive to subtle changes in the activity of AP.

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Child; Diphosphates; Ethanolamines; Female; Humans; Hypophosphatasia; Leukocytes; Male; Middle Aged; Pedigree

The serum concentration of parathormone is usually normal in hypophosphatasia, a rare disease with a defect of bone mineralisation and low serum alkaline phosphatase activity. Nevertheless there are three cases in the literature presenting a hyperparathyroidism with or without hypercalcemia. No anomaly of parathyroid was found at autopsy. The authors describe the first cases of hypophosphatasia with low serum concentration of parathormone and raise the possibility of a trouble in the calcium-parathormone feed-back. They also emphasize the interest of the urinary pyrophosphate excretion. Its increase seem to be the most constant and the most specific biological disorder.

Topics: Adult; Child, Preschool; Diphosphates; Ethanolamines; Female; Humans; Hypophosphatemia, Familial; Infant; Male; Parathyroid Hormone

Hypophosphatasia represents an inborn enzymatic deficiency characterized by a reduced activity of alkaline phosphatase in serum and tissue and an increased urinary excretion of phosphoethanolamine. 278 cases have been described until the end of 1980. Based on the age of manifestation and the predominant clinical findings the following classification is possible: The prenatal form (49 cases) with caput membranaceum, skeletal deformities and respiratory distress has a mortality of 100%. The early infantile form (94 cases) shows rickets-like osseous anomalies, dystrophy, craniostenosis, nephrocalcinosis, mortality amounting to 40%. Diagnostic features of the infantile-juvenile form (112 cases) are premature loss of deciduous teeth, bone deformities, rickets-like findings, and short stature. Mortality is only 1%. The adult form (23 cases) often remains undiscovered and has a good prognosis. It presents with pseudofractures and pains in the bones as chief symptoms. Heredity is autosomal recessive in all four types of hypophosphatasia. Possibly in the adult form there is an additional autosomal dominant inheritance. Alkaline phosphatase deficiency affects all tissues excepting the intestinal isoenzyme. Urinary excretion of phosphoethanolamine is elevated. Values for calcium and inorganic phosphorus in serum are usually normal or only slightly increased. Marked hypercalcemia is observed in severely diseased patients affected by the early infantile form. In these cases hypercalcemia often leads to nephrocalcinosis and renal insufficiency. Since alkaline phosphatase is equally active as pyrophosphatase, reduced phosphatase activity induces an accumulation of pyrophosphate in serum and its increased excretion in urine. The precise pathogenetic mechanisms of hypophosphatasia are still unknown. Possibly, the accumulation of pyrophosphate implies a disorder of calcification. Postnatal diagnosis is based on clinical findings in association with decreased alkaline phosphatase activity and increased phosphoethanolamine excretion. For the detection of heterozygotes additional biochemical markers should be tested. These include the determination of alkaline phosphatase in leucocytes and cultured skin fibroblasts, the calculation of tubular phosphate reabsorption and the analysis of pyrophosphate and pyrophosphatases. The difficulty in ascertaining the carrier state is that the measurement of a single parameter may give normal results.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adolescent; Adult; Alkaline Phosphatase; Calcium; Child; Child, Preschool; Diagnosis, Differential; Diphosphates; Ethanolamines; Female; Humans; Hypophosphatasia; Infant; Infant, Newborn; Isoenzymes; Ossification, Heterotopic; Phosphates; Pregnancy; Prenatal Diagnosis; Prognosis; Pyrophosphatases

Topics: Alkaline Phosphatase; Diphosphates; Enzymes; Ethanolamines; Gene Expression Regulation; Neurospora; Neurospora crassa; Phosphates; Phosphorus

Topics: Alkaline Phosphatase; Diphosphates; Ethanolamines; Female; Humans; Hypophosphatasia; Organophosphorus Compounds; Pedigree; Pyrophosphatases