Phosphate abnormal metabolism

There are a number of glycogen storage diseases. Of those that are discussed, three involve deficiencies of systems directly related to glycogen degradation another involves abnormal metabolism of the product of glycogen degradationspecifically, the hexose phosphate. 

Patients with tumor lysis syndrome experience a wide range of metabolic abnormalities. The massive cell lysis that occurs leads to the release of intracellular electrolytes, resulting in hyperkalemia and hyperphosphatemia. High concentrations of phosphate bind to calcium, leading to hypocalcemia and calcium phosphate precipitation in the renal tubule. Purine nucleic acids are also released that are subsequently metabolized to uric acid... 

Potassium is the second most abundant cation in the body and is found primarily in the intracellular fluid. Potassium has many important physiologic functions, including regulation of cell membrane electrical action potential (especially in the myocardium), muscular function, cellular metabolism, and glycogen and protein synthesis. Potassium in PN can be provided as chloride, acetate, and phosphate salts. One millimole of potassium phosphate provides 1.47 mEq of elemental potassium. Generally, the concentration of potassium in peripheral PN (PPN) admixtures should not exceed 80 mEq/L (80 mmol/L). While it is safer to also stick to the 80 mEq/L (80 mmol/L) limit for administration through a central vein, the maximum recommended potassium concentration for infusion via a central vein is 150 mEq/L (150 mmol/L).14 Patients with abnormal potassium losses (e.g., loop or thiazide diuretic therapy) may have higher requirements, and patients with renal failure may require potassium restriction. 

Kato, T., Shioiri, T., Murashita, J., Hamakawa, H., Takahashi, Y., Inubushi, T., and Takahashi, S. (1995) Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded 31P-MRS. Psychol Med 25 557—566. 

R., Strittmatter, W. J., Blass, J. P. Glyceraldehyde-3-phosphate dehydrogenase abnormality in metabolically stressed Huntington disease fibroblasts. Dev. Neurosci. 1998, 20 462-468. 

In vitamin Be-deflcient experimental animals, there are skin lesions (e.g., acrodynia in the rat) and fissures or ulceration at the corners of the mouth and over the tongue, as well as a number of endocrine abnormalities defects in the metabolism of tryptophan (Section 9.5.4), methionine (Section 9.5.5), and other amino acids hypochromic microcytic anemia (the first step of heme biosynthesis is pyridoxal phosphate dependent) changes in leukocyte count and activity a tendency to epileptiform convulsions and peripheral nervous system damage resulting in ataxia and sensory neuropathy. There is also impairment of immune responses, as a result of reduced activity of serine hydroxymethyltransferase and hence reduced availability of one-carbon substituted folate for nucleic acid synthesis (Section 10.3.3). It has been suggested... 

Early studies of vitamin Be requirements used the development of abnormalities of tryptophan or methionine metabolism during depletion, and normalization during repletion with graded intakes of the vitamin. Although tryptophan and methionine load tests are unreliable as indices of vitamin Be status in epidemiological studies (Section 9.5.4 and Section 9.5.5), under the controlled conditions of depletion/repletion studies they do give a useful indication of the state of vitamin Be nutrition. More recent studies have used more sensitive indices of status, including the plasma concentration of pyridoxal phosphate, urinary excretion of 4-pyridoxic acid, and erythrocyte transaminase activation coefficient. 

It was also observed (W6) that at termination of normal pregnancy, vitamin Be values were significantly depressed in maternal leucocytes and plasma. In blood of women in the last trimester of pregnancy, however, normal average amounts of the vitamin were found, although these individuals had a distinct abnormality in tryptophan metabolism. Amounts of pyridoxal phosphate are high in cord blood. 

Despite normal plasma pyridoxal 5-phosphate values, the urinary excretion of xanthurenic acid was found abnormally elevated in 3 epileptic children with disturbed tryptophan metabolism (HO). Administration of pyridoxine restored xanthurenuria to normal and raised plasma pyridoxal 5-phosphate levels. 

For the authors (PIO) the simplest explanation of the data on tryptophan metabolism in these 3 patients would be as follows in scleroderma (acrosclerosis) there was an abnormal urinary excretion of kynurenine and its metabolites after oral ingestion of tryptophan. The administration of pyridoxine or pyridoxine plus nicotinamide partially corrected the metabolic abnormality. The efficacy of pyridoxine plus Na2EDTA could be explained on the basis of a decrease in tissue calcium and zinc (and possibly other cations), enabling the metal ions, normally functioning with pyridoxal phosphate, as magnesium ions, to be utilized more advantageously. 

Another metabolic disorder that is hereditary and little known is hypophosphatasia. Hypophosphatasia is an inherited metabolic (chemical) bone disease that results from low levels of an enzyme called alkaline phosphatase (ALP). ALP is normally present in large amounts in bones and the liver. In hypophosphatasia, abnormalities in the gene that makes ALP lead to the production of inactive ALP. Subsequently, several chemicals, including phosphoethanolamine, pyridoxal 57-phosphate (a form of vitamin B ) and inorganic pyrophosphate, accumulate in the body and are found in large amounts in the blood and urine. It appears that the accumulation of inorganic pyrophosphate is the cause of the characteristic defective calcification of bones seen in infants and children (rickets) and in adults (osteomalacia). 

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