Alkaline phosphatase vitamins

In the bile-duct-ligated rat, hepatic mitochondrial lipid peroxides are increased and correlate with serum levels of alkaline phosphatase, bilirubin and alanine aminotransferase (Sokol et al., 1991). Dietary vitamin E deficiency resulted in relatively higher lipid peroxide and bilirubin... 

Pantothenate in blood and tissues is bound (R9) and released by autolysis or hydrolysis. More vitamin could be released by use of an alkaline phosphatase and an enzyme from avian liver (L6). This method liberates pantothenate from coenzyme A in a variety of foods and tissues (N3, N4). A comparison of hydrolytic methods in blood suggested autolysis to be the most advantageous method (N3) in our hands, treatment with Clarase gave more reliable results as compared with autolysis, acid hydrolysis, treatment with Mylase P, or combination of Clarase and papain, or liver enzyme and alkaline phosphatase. In urine, pantothenic acid is unbound our results show no increase with Clarase treatment. The vitamin has presumably a low threshold. Pantothenic acid shows the same concentration in blood and cerebrospinal fluid. 

Osteomalacia is the condition in which bone becomes demineralised due to deficiency of vitamin D. In this condition parathyroid hormone (PTH) acts on the bone to maintain serum calcium, resulting in demineralisation. Serum calcium is usually normal or slightly low alkaline phosphatase levels are high, reflecting excessive osteoblast activity, and serum phosphate falls as an effect of PTH on the kidney. The same condition in children results in defects in long bone formation, and is termed rickets. 

The acoustic micrograph in Fig. 1.5(a) came from a 5-week-old preparation. It was fixed in alcohol, and stained for alkaline phosphatase and, with von Kossa stain, for biomineral material. The biomineral material of interest here is hydroxyapatite, the principal crystalline mineral constituent of bone. The ordered structure visible within the matrix is not seen with either the light or electron microscopes. But the acoustic microscope can also work perfectly well with unfixed, unstained specimens. Figure 1.5(b) is an acoustic micrograph of matrix and cells from a 17-year-old male. In addition to the standard ingredients of culture medium, these cells were specifically stimulated with beta-glycerolphosphate and a vitamin C preparation. Because the acoustic... 

Studies of acid and alkaline phosphatase activities in bone have been used previously to investigate the action of various substances such as parathormone223, 224, calcitonin225, diphosphonates226 and vitamin A227. Calvarial acid and alkaline phosphatase activities are modified after in vivo injections of vitamin D3 metabolites to rats fed a vitamin D-deficient, low-calcium (0.02 %)diet. Changes in these activities are observed after administration of small doses, i. e. 

As a brief introductory summary, vitamin D substances perform the following fundamental physiological functions (1) promote normal growth (via bone growth) (2) enhance calcium and phosphorus absorption from the intestine (3) serve to prevent rickets (4) increase tubular phosphorus reabsorpiion (5) increase citrate blood levels (6) maintain and activate alkaline phosphatase m bone (7) maintain serum calcium and phosphorus levels. A deficiency of D substances may be manifested in the form of rickets, osteomalacia, and hypoparathyroidism. Vitamin D substances are required by vertebrates, who synthesize these substances in the skin when under ultraviolet radiation, Animals requiring exogenous sources include infant vertebrates and deficient adult vertebrates, Included there are vitamin D (calciferol ergocalciferol) and vitamin D< (activated 7-dehydrocholesterol cholecalciferol). 

The transfer of phosphate is stimulated by l,25-(OH)2D3, but little is known about the mechanism. Vitamin D also stimulates the activities of alkaline phosphatase and Ca2+-ATPase. This may be involved in the supply of inorganic phosphate. 

Alteration of serum enzyme activity has been shown to be a sensitive parameter of tissue injury (20). While the activities of such enzymes as pyruvate kinase, lactate dehydrogenase, glutamate oxaloacetate transaminase, alkaline phosphatase, and creatine phosphokinase in rat serum were significantly altered by the deprivation of dietary vitamin E, the activities of these enzymes were not influenced by smoking exposure under the experimental conditions (Table I). 

Vitamin D regulates calcium and phosphorus absorption and deposition and serum alkaline phosphatase levels. The recommended daily allowance is 5 /xg, increasing to 10 to 15 /xg in older age.109 Vitamin D3 is synthesized under UVB irradiation in the skin where it is stored and released into the circulation in a complex with the vitamin D binding protein. In liver it is hydroxylated to 25(OH)-cholecalciferol, the hormonal precursor, followed by another hydroxylation step in the... 

Vitamin D also exerts an effect upon the intestinal absorption of phosphorus probably in relation with the stimulation of alkaline phosphatase synthesis [22,35],... 

The biochemical features of calcium-deficiency and vitamin D deficiency are very similar. Both disorders result in a low-to-normal serum calcium concentration, an elevated PTH level, a decreased or normal phosphorus concentration, and increased alkaline phosphatase activity. The serum concentration of 25-hydroxyvitamin D is normal or slightly decreased in calcium-deficiency rickets but is markedly decreased in vitamin D deficiency. On the other hand, the serum concentration of 1,25-dihydroxyvitamin D is greatly elevated in calcium-deficiency rickets but is normal or even slightly decreased in vitamin D-deficiency rickets. 

Depending on the nature of the chronic liver disease, the biliary tract may or may not be affected, and hence bilirubin and alkaline phosphatase may be normal or raised. For example, a patient with primary biliary cirrhosis (PBC) can have an alkaline phosphatase and bilirubin raised to twice ULN. Where there is biliary involvement there is the potential for reduced fat-soluble vitamin absorption. ITence a raised alkaline phosphatase may have occurred over time owing to decreased vitamin D absorption affecting bone development, rather than being associated with the liver. Likewise, the clotting may be abnormal because of vitamin K deficiency. 

The plasma concentration of calcidiol is the most sensitive and usefiil index of vitamin D status, and is correlated with elevated plasma parathyroid hormone and alkaline phosphatase activity (Table 3.4). As shown in Table 3.2, the reference range of plasma calcidiol is between 20 to 150 nmol per L, with a twofold seasonal variation in temperate regions. Concentrations below 20 nmol per L are considered to indicate impending deficiency, and osteomalacia is seen in adults when plasma calcidiol falls below 10 nmol per L. In children, clinical signs of rickets are seen when plasma calcidiol faUs below 20 nmol per L. The plasma concentration of calcitriol does not give a useful indication of vitamin D status. The reference range is between 38 to 144 pmol per L and is maintained because of the stimulation of calcidiol 1-hydroxylation by parathyroid hormone secreted in response to faUing concentrations of calcium (Holick, 1990). 

Tissue uptake of vitamin Be is again by carrier-mediated diffusion of pyridoxal (and other unphosphorylated vitamers), followed by metabolic trapping by phosphorylation. Circulating pyridoxal and pyridoxamine phosphates are hydrolyzed by extracellular alkaline phosphatase. All tissues have pyridoxine kinase activity, but pyridoxine phosphate oxidase is found mainly in the liver, kidney, and brain. 

Narisawa S, Wennberg C, and Millan JL (2001) Abnormal vitamin Be metabolism in alkaline phosphatase knock-out mice causes multiple abnormalities, but not the impaired bone mineralization./oMrwfll of Pathology 193, 125-33. 

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). 

Chronic intoxication with vitamin A has been reported to cause variously hypercalcemia, hyperglycae-mia, increased alkaline phosphatase, hypoproteinemia, hypoprothrombinemia, increased sulfobromphthalein retention, raised serum transaminases, low serum ascorbic acid, reduced protein content of the cerebrospinal fluid, raised urinary hydroxyproline, and hypercalciuria (SED-8, 800) (14). It is not always clear, however, whether these deviations are a cause or an effect of hypervitaminosis A. 

Excessive doses of vitamin A lead to accelerated resorption of trabecular and cortical bone because of increased osteoclastic activity. A raised alkaline phosphatase, increased urinary hydroxyproline concentrations, and hypercalciuria correlate with these findings (54). One study suggested that high dietary intake of retinol might be associated with osteoporosis (55). 

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