UNLABELLED Targeting cancer cells with vitamin B12 (cobalamin) is hampered by unwanted physiologic tissue uptake mediated by transcobalamin. Adhering to good manufacturing practice, we have developed a new (99m)Tc-cobalamin derivative ((99m)Tc(CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino-acetato] cobalamin, (99m)Tc-PAMA-cobalamin). The derivative shows no binding to transcobalamin but is rec...

1. The isolated perfused rat liver and suspensions of isolated rat hepatocytes fail to form glucose from histidine, in contrast with the liver in vivo. Both rat liver preparations readily metabolize histidine. The main end product is N-formiminoglutamate. In this respect the liver preparations behave like the liver of cobalamin- or folate-deficient mammals. 2. Additions of L-methionine in physi...

The level of the vitamin B12 transport protein BtuB in the outer membrane of Escherichia coli is strongly reduced by growth in the presence of cobalamins. Previous analyses of regulatory mutants and of btuB-lacZ fusions indicated that the primary site of btuB gene regulation was at the translational level, and this required sequences throughout the 240-nucleotide (nt) leader region. Cobalamin-d...

We have read with interest Hvas and Nexo’s very informative update article about the diagnosis and treatment of vitamin B12 deficiency. Authors also stated that vitamin B12 deficiency is an important public health problem. It is well known that diagnostic approach to this deficiency is very important to reveal the underlying cause that is usually attributed to malabsorption. Carmel et al.’s fou...

The challenges in medical management of cobalamin deficiency lie in attention to the unique pathophysiology that underlies cobalamin deficiency, more than in the mechanics of therapy. The central physiologic principles are that clinically important deficiency is more likely to occur (and progress) when intrinsic factor-driven absorption fails than when diet is poor and that most causes take yea...

Cultured fibroblasts from a recently described patient with homocystinuria and megaloblastic anemia of infancy without methylmalonic aciduria were previously shown to have normal cobalamin uptake and a specific decrease in the proportion of intracellular methylcobalamin. As in control cells but unlike in those from patients with combined homocystinuria and methylmalonic aciduria (cobalamin C an...

AIMS To compare the efficacy of sublingual and oral administration of 500 micro g of cobalamin in subjects with cobalamin deficiency. MATERIALS AND RESULTS Thirty subjects with low serum concentrations of cobalamin participated in the study. Subjects were randomly allocated to receive one tablet daily of 500 micro g cobalamin sublingually or orally, or two tablets daily of a vitamin B complex...

n engl j med 367;4 nejm.org july 26, 2012 385 Failures of Cobalamin Assays in Pernicious Anemia To the Editor: Cobalamin (vitamin B12) assays have been central to the diagnosis of clinical cobalamin deficiency such as pernicious anemia because the diagnostic sensitivities of older assays have been approximately 95%.1 However, the competitive-binding luminescence assay (CBLA) replaced older micr...

Cobalamin synthesis probably requires 20 to 30 different enzymatic steps. Pseudomonas putida and Agrobacterium tumefaciens mutants deficient in cobalamin synthesis (Cob have been isolated. In P. putida, Cob mutants were identified as being unable to use ethanolamine as a source of nitrogen in the absence of added cobalamin (deamination of ethanolamine requires coenzyme B12 as a cofactor). In A....