A New Principle for Measurement of Cobalamin and Corrinoids, Used for Studies of Cobalamin Analogs on Serum Haptocorrin

Hardlei, Tore Forsingdal; Nexø, Ebba

doi:10.1373/clinchem.2008.114132

Cited by 27 publications

(30 citation statements)

References 25 publications

(30 reference statements)

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“…Moreover, the present study demonstrated a strong correlation between aHC and totalHC, a result consistent with previously reported findings (19 ). It is possible that these associations may be explained by the molecular dynamics in the blood.…”

Section: Impairmentsupporting

confidence: 93%

“…TC saturation (TCsat) was calculated as: 100 ϫ holoTC/totalTC (reference interval 2%-17%). Total corrinoids on HC (corHC) (reference interval 210 -740 pmol/L) and B 12 on HC (B 12 -HC) (reference interval 60 -400 pmol/L) were measured simultaneously with an analytical imprecision Ͻ13% (19 ). The total amount of B 12 analogs on HC (aHC) (reference interval 100 -380 pmol/L) was calculated as the difference between corHC and B 12 -HC.…”

Section: Laboratory Methodsmentioning

confidence: 99%

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Association of Cognitive Impairment with Combinations of Vitamin B12–Related Parameters

et al. 2011

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BACKGROUND: Low vitamin B 12 concentrations have been associated with higher risks of cognitive impairment, but whether these associations are causal is uncertain. The associations of cognitive impairment with combinations of vitamin B 12 , holotranscobalamin, methylmalonic acid, and total homocysteine, and with the vitamin B 12 transport proteins transcobalamin and haptocorrin, have not been previously studied.

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Section: Impairmentsupporting

confidence: 93%

Section: Laboratory Methodsmentioning

confidence: 99%

Association of Cognitive Impairment with Combinations of Vitamin B12–Related Parameters

et al. 2011

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“…These data indicate that CN2-Cbi may be a prototype for a novel type of sGC-regulating therapeutic agent. It is unlikely that physiological concentrations of circulating cobinamides (Ͻ30 pM) or B 12 vitamins (ϳ300 pM) (Hardlei and Nexo, 2009) have any effects on sGC func- Because of high affinity to cyano groups, cobinamides are used for cyanide detoxification (Broderick et al, 2006) and doses of 800 mg/kg are deemed safe for laboratory animals (Brenner et al, 2010). Previous studies reported that nitrosyl-cobinamide functions as an NO donor (Broderick et al, 2007), increasing vasodilation and vasodilator-stimulated phosphoproteinphosphorylation, presumably through NO-dependent activation of sGC.…”

Section: Discussionmentioning

confidence: 99%

Cobinamides Are Novel Coactivators of Nitric Oxide Receptor That Target Soluble Guanylyl Cyclase Catalytic Domain

Sharina

Sobolevsky

Doursout³

et al. 2011

J Pharmacol Exp Ther

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Soluble guanylyl cyclase (sGC), a ubiquitously expressed hemecontaining receptor for nitric oxide (NO), is a key mediator of NOdependent processes. In addition to NO, a number of synthetic compounds that target the heme-binding region of sGC and activate it in a NO-independent fashion have been described. We report here that dicyanocobinamide (CN2-Cbi), a naturally occurring intermediate of vitamin B 12 synthesis, acts as a sGC coactivator both in vitro and in intact cells. Heme depletion or heme oxidation does not affect CN2-Cbi-dependent activation. Deletion mutagenesis demonstrates that CN2-Cbi targets a new regulatory site and functions though a novel mechanism of sGC activation. Unlike all known sGC regulators that target the N-terminal regulatory regions, CN2-Cbi directly targets the catalytic domain of sGC, resembling the effect of forskolin on adenylyl cyclases. CN2-Cbi synergistically enhances sGC activation by NO-independent regulators 3-(4-amino-5-cyclopropylpyrimidine- (cinaciguat or BAY58-2667), and 5-chloro-2-(5-chloro-thiophene-2-sulfonylamino-N-(4-(morpholine-4-sulfonyl)-phenyl)-benzamide sodium salt (ataciguat or HMR-1766). BAY41-2272 and CN2-Cbi act reciprocally by decreasing the EC 50 values. CN2-Cbi increases intracellular cGMP levels and displays vasorelaxing activity in phenylephrine-constricted rat aortic rings in an endothelium-independent manner. Both effects are synergistically potentiated by BAY41-2272. These studies uncover a new mode of sGC regulation and provide a new tool for understanding the mechanism of sGC activation and function. CN2-Cbi also offers new possibilities for its therapeutic applications in augmenting the effect of other sGC-targeting drugs.

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“…Therefore, we collected fortysix post-column fractions every 20 s (320 µl/fraction) between 9 and 25 min after injection. The samples were lyophilised and dissolved in 240 µl of 0·1 % PBS with 0·1 % bovine serum albumin (PBA) before measurement of B 12 , employing in-house haptocorrin ELISA (15,17) with a detection limit of 8 pmol/l B 12 . In brief, 100 µl (sample or calibrator) was incubated with apohaptocorrin, and excessive apo-haptocorrin was removed with B 12 -coated magnetic beads.…”

Section: Determination Of Vitamin B 12 Forms In Rat Tissuementioning

confidence: 99%

The tissue profile of metabolically active coenzyme forms of vitamin B₁₂ differs in vitamin B₁₂-depleted rats treated with hydroxo-B₁₂ or cyano-B₁₂

et al. 2018

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Recent rat studies show different tissue distributions of vitamin B 12 (B 12 ), administered orally as hydroxo-B 12 ) (predominant in food) and cyano-B 12 ) (common in supplements). Here we examine male Wistar rats kept on a low-B 12 diet for 4 weeks followed by a 2-week period on diets with HO-B 12 (n 9) or CN-B 12 (n 9), or maintained on a low-B 12 diet (n 9). Plasma B 12 was analysed before, during and after the study. The content of B 12 and its variants (HO-B 12 , glutathionyl-B 12 , CN-B 12 , 5'-deoxyadenosyl-B 12 (ADO-B 12 ), and methyl-B 12 (CH 3 -B 12 )) were assessed in the tissues at the end of the study. A period of 4 weeks on the low-B 12 diet reduced plasma B 12 by 58 % (from median 1323 (range 602-1791) to 562 (range 267-865) pmol/l, n 27). After 2 weeks on a high-B 12 diet (week 6 v. week 4), plasma B 12 increased by 68 % (HO-B 12 ) and 131 % (CN-B 12 ). Total B 12 in the tissues accumulated differently: HO-B 12 > CN-B 12 (liver, spleen), HO-B 12 < CN-B 12 (kidneys), and HO-B 12 ≈CN-B 12 (brain, heart). Notably, more than half of the administered CN-B 12 remained in this form in the kidneys, whereas HO-B 12 was largely converted to the bioactive ADO-B 12 . Only <10 % of the other cofactor, CH 3 -B 12 , were found in the tissues. In conclusion, dietary CN-B 12 caused a higher increase in plasma and total kidney B 12 but provided less than half of the active coenzymes in comparison to dietary HO-B 12 . These data argue that HO-B 12 may provide a better tissue supply of B 12 than CN-B 12 , thereby underscoring the lack of a direct relation between plasma B 12 and tissue B 12 . ]-coordinating anions. These reactions occur irrespectively of light (6) . All forms of B 12 are metabolically transformed into and CH 3 -B 12 in the cell (3) . Here, ADO-B 12 acts as a cofactor for methylmalonyl-CoA mutase in the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondria. CH 3 -B 12 acts as a cofactor for methionine synthase in the folatedependent methylation of homocysteine to methionine in the cytoplasm (1,2) .Both human and animal studies have demonstrated that synthetic and natural forms of B 12 are absorbed equally (7)(8)(9)(10)(11) . However, our recent data show that HO-B 12 accumulates in the liver to a higher degree than CN-B 12 , but that the patterns are opposite in the brain and plasma. These observations were based on the administration of acute doses of radiolabelled HO-B 12 and CN-B 12 to rats (10,11) . In accordance with this, acute human studies showed CN-B 12 to cause a 2-3-fold higher increase in the active circulating B 12 , holotranscobalamin, relative to HO-B 12 upon oral administration (12) . These findings Abbreviations: ADO-B 12 ,

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A New Principle for Measurement of Cobalamin and Corrinoids, Used for Studies of Cobalamin Analogs on Serum Haptocorrin

Abstract: BACKGROUND: Transcobalamin (TC) and haptocorrin (HC) are serum corrinoid-binding proteins. We developed new methods for measurement of the corrinoids bound to HC and TC.

Cited by 27 publications

References 25 publications

Association of Cognitive Impairment with Combinations of Vitamin B12–Related Parameters

Association of Cognitive Impairment with Combinations of Vitamin B12–Related Parameters

Cobinamides Are Novel Coactivators of Nitric Oxide Receptor That Target Soluble Guanylyl Cyclase Catalytic Domain

The tissue profile of metabolically active coenzyme forms of vitamin B₁₂ differs in vitamin B₁₂-depleted rats treated with hydroxo-B₁₂ or cyano-B₁₂

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A New Principle for Measurement of Cobalamin and Corrinoids, Used for Studies of Cobalamin Analogs on Serum Haptocorrin

Abstract: BACKGROUND: Transcobalamin (TC) and haptocorrin (HC) are serum corrinoid-binding proteins. We developed new methods for measurement of the corrinoids bound to HC and TC.

Cited by 27 publications

References 25 publications

Association of Cognitive Impairment with Combinations of Vitamin B12–Related Parameters

Association of Cognitive Impairment with Combinations of Vitamin B12–Related Parameters

Cobinamides Are Novel Coactivators of Nitric Oxide Receptor That Target Soluble Guanylyl Cyclase Catalytic Domain

The tissue profile of metabolically active coenzyme forms of vitamin B12 differs in vitamin B12-depleted rats treated with hydroxo-B12 or cyano-B12

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The tissue profile of metabolically active coenzyme forms of vitamin B₁₂ differs in vitamin B₁₂-depleted rats treated with hydroxo-B₁₂ or cyano-B₁₂