Studies on Derivation of Transcobalamin III from Granulocytes ENHANCEMENT BY LITHIUM AND ELIMINATION BY FLUORIDE OF IN VITRO INCREMENTS IN VITAMIN B12-BINDING CAPACITY

Scott, J. M.; Bloomfield, F. J.; Stebbins, Richard Poate; Herbert, Victor

doi:10.1172/jci107543

Cited by 76 publications

(13 citation statements)

References 26 publications

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“…This lack of selectivity appears to enhance the antibacterial function of GRP since this protein can bind Cbl and Cbl analogues and make them unavailable for certain bacteria that require them for growth. GRP has the following characteristics that favor it over TC II in terms of competing for binding of Cbl analogues in vivo: (a) GRP has a higher affinity for Cbl and Cbl analogues than TC II; (b) GRP retains its high affinity over a pH range of [2][3][4][5][6][7][8][9][10][11][12] whereas that of TC II decreases markedly below pH 5 (39) and is thus relatively ineffective in areas of necrosis or infection; and (c) GRP is located in the specific granules of granulocytes (40) from which it is released into phagosomes and also extracellularly (41,42). The enhanced ability of GRP to bind Cbl analogues enables them to be transported exclusively to hepatocytes rather than to other tissues which may be more susceptable to their toxic effects.…”

Section: Resultsmentioning

confidence: 99%

Absorption, Plasma Transport, and Cellular Retention of Cobalamin Analogues in the Rabbit

Kolhouse¹,

Allen²

1977

J. Clin. Invest.

136

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Section: Resultsmentioning

confidence: 99%

Absorption, Plasma Transport, and Cellular Retention of Cobalamin Analogues in the Rabbit

Kolhouse¹,

Allen²

1977

J. Clin. Invest.

136

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“…Transcobalamin III binds weakly to DEAE, has 1-mobility on serum electrophoresis, is essentially unsaturated with Br2, and appears to be released in large part from granulocytes in vitro after blood is collected (20). Transcobalamin I binds tightly to DEAE, has a-mobility on serum electrophoresis, is 70-100% saturated with B12, and does not appear to be released from granulocytes in vitro in significant amounts (21). Recent studies (22) have demonstrated that normal plasma transcobalamin I contains more sialic acid and less fucose than transcobalamin III and that transcobalamin I has a carbohydrate composition that is essentially identical to those of the two hepatoma Ba2 BPs.…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of a novel vitamin B12-binding protein associated with hepatocellular carcinoma.

Burger¹,

Waxman²,

Gilbert³

et al. 1975

J. Clin. Invest.

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A B S T R A C T High levels of a novel vitamin B12-binding protein (hepatoma B112 BP) have been observed recently in plasma obtained from three adolescent patients with hepatocellular carcinoma. This protein has now been isolated in homogeneous form from the plasma and pleural fluid of two of these patients by the use of affinity chromatography with vitamin B12-Sepharose. The hepatoma Bu BP belongs to the R-type group of B12-binding proteins and is essentially indistinguishable from the recently isolated human milk and saliva R-type proteins in terms of: (a) immunologic properties based on immunodiffusion and immunoprecipitation assays; (b) amino acid composition; (c) molecular weight based on amino acid and carbohydrate content; and (d) absorption spectra. Both hepatoma B22 BPs contain more sialic acid and less fucose than the milk and saliva B12 BPs. All four proteins contain similar amounts of galactose, mannose, galactosamine, and glucosamine. Differences in sialic acid content appear to account for the differences in electrophoretic mobility that were observed among the four proteins. Differences in total carbohydrate content appear to account for the differences in apparent molecular weight that were observed with both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.Tumor tissue from one of the patients contained 10 times as much R-type protein as did normal liver tissue from the same patient. This suggests, although it does not prove, that synthesis by the tumor is the Received for publication 30 December 1974 and in revised form 8 July 1975. cause of the high levels of R-type protein found in the plasma of certain patients with hepatocellular carcinoma. Plasma survival studies performed with rabbits indicate that the hepatoma B,2 BP has a prolonged plasma survival and suggests that this parameter is also of importance. INTRODUCTIONA recent report (1) described three adolescents who presented with hepatocellular carcinomas, normal leukocyte counts, extraordinary elevations of serum vitamin B, (B,2),' (15-53 ng/ml, normal 0.3-0.9 ng/ml), and serum unsaturated B12-binding capacity, (5-480 ng/ml, normal 0.8-1.4 ng/ml). Studies (2) using sera from two of these patients indicate that the elevations of serum B12 and unsaturated B,2-binding capacity are due to the presence of a B,2-binding protein (B12 BP) that belongs to the R-type' class of immunologically related Bl2 BPs that are normally present in a number of human tissues and body fluids (3). These studies also demonstrated that the hepatoma-related B12 BP differs from the R-type B,2 BP found in increased

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“…Manual methods to determine UBBC are available 17. The reference range for UBBC is 670–1200 ng/L;18 for plasma collected into EDTA-sodium fluoride, it is 505–1208 ng/L;19 for haptocorrin, 49–132 ng/L; and for transcobalamin, 402–930 ng/L.…”

Section: Serum B12 Assaysmentioning

confidence: 99%

Laboratory assessment of vitamin B₁₂status

Harrington

2016

J Clin Pathol

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The detection and correction of vitamin B 12 (B 12 ) deficiency prevents megaloblastic anaemia and potentially irreversible neuropathy and neuropsychiatric changes. B 12 status is commonly estimated using the abundance of the vitamin in serum, with ∼148 pmol/L (200 ng/L) typically set as the threshold for diagnosing deficiency. Serum B 12 assays measure the sum of haptocorrin-bound and transcobalamin-bound (known as holotranscobalamin) B 12 . It is only holotranscobalamin that is taken up by cells to meet metabolic demand. Although receiver operator characteristic curves show holotranscobalamin measurement to be a moderately more reliable marker of B 12 status than serum B 12 , both assays have an indeterminate range. Biochemical evidence of metabolic abnormalities consistent with B 12 insufficiency is frequently detected despite an apparently sufficient abundance of the vitamin. Laboratory B 12 status markers that reflect cellular utilisation rather than abundance are available. Two forms of B 12 act as coenzymes for two different reactions. Methionine synthase requires methylcobalamin for the remethylation of methionine from homocysteine. A homocysteine concentration >20 mmol/L may suggest B 12 deficiency in folate-replete patients. In the second B 12 -dependent reaction, methylmalonyl-CoA mutase uses adenosylcobalamin to convert methylmalonyl-CoA to succinyl-CoA. In B 12 deficiency excess methylmalonylCoA is hydrolysed to methylmalonic acid. A serum concentration >280 nmol/L may suggest suboptimal status in young patients with normal renal function. No single laboratory marker is suitable for the assessment of B 12 status in all patients. Sequential assay selection algorithms or the combination of multiple markers into a single diagnostic indicator are both approaches that can be used to mitigate inherent limitations of each marker when used independently.

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Studies on Derivation of Transcobalamin III from Granulocytes ENHANCEMENT BY LITHIUM AND ELIMINATION BY FLUORIDE OF IN VITRO INCREMENTS IN VITAMIN B12-BINDING CAPACITY

Cited by 76 publications

References 26 publications

Absorption, Plasma Transport, and Cellular Retention of Cobalamin Analogues in the Rabbit

Absorption, Plasma Transport, and Cellular Retention of Cobalamin Analogues in the Rabbit

Isolation and characterization of a novel vitamin B12-binding protein associated with hepatocellular carcinoma.

Laboratory assessment of vitamin B₁₂status

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Studies on Derivation of Transcobalamin III from Granulocytes ENHANCEMENT BY LITHIUM AND ELIMINATION BY FLUORIDE OF IN VITRO INCREMENTS IN VITAMIN B12-BINDING CAPACITY

Cited by 76 publications

References 26 publications

Absorption, Plasma Transport, and Cellular Retention of Cobalamin Analogues in the Rabbit

Absorption, Plasma Transport, and Cellular Retention of Cobalamin Analogues in the Rabbit

Isolation and characterization of a novel vitamin B12-binding protein associated with hepatocellular carcinoma.

Laboratory assessment of vitamin B12status

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Laboratory assessment of vitamin B₁₂status