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Vitamin Deficiency in Patients with Terminal Cancer
Published in Victor R. Preedy, Handbook of Nutrition and Diet in Palliative Care, 2019
Renata Gorska, Dominic J. Harrington
The measurement of serum levels of vitamin B12 is commonly used as a marker of vitamin B12 status. It is often not widely appreciated that circulatory vitamin B12 is predominately bound to two proteins and that “front-line” laboratory assays do not discriminate between these forms. Although ∼80% of vitamin B12 is carried by haptocorrin (holohaptocorrin, abbreviated as HC), extrahepatic cellular receptors have not been described. HoloTC facilitates receptor-mediated uptake of cobalamin therein to all cells. Circulatory levels of HC decline slowly in response to the onset of a deficient state, typically taking three to six years to fall below the lower limit of most assay reference ranges. Circulatory levels of holoTC fall quickly and give an early indication of deficiency, although in assays that cannot discriminate between these two forms this decline is masked by the more abundant HC. Deficiency of vitamin B12 is common in patients with serum levels within the reference range and can be revealed by measuring holoTC, methylmalonic acid assay (MMA) and/or homocysteine (Harrington 2017).
Normal and Abnormal Intestinal Absorption by Humans
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
David W. Hobson, Valerie L. Hobson Balldin
Vitamin B12 absorption involves an active transport process. Four physiologically important forms of vitamin B12 are cyanocobalamin, hydroxycobalamin, methylcobalamin, and deoxyadenosylcobalamin. Up to 5 mg of Vitamin B12 is stored in the liver. About 70% of the Vitamin B12 present in the bile is reabsorbed. This liver storage is thought to be sufficient for 3–6 years [37]. Most cobalamins are bound to proteins and absorbed in the intestine. The low pH of the stomach and pepsin release cobalamins; which are bound to R proteins, i.e., haptocorrin (HC) secreted from salivary glands and gastric juice. Intrinsic factor (IF) is a cobalamin-binding protein secreted by the gastric parietal cells [38]. Its secretory rate usually parallels that of HC. Dietary cobalamin bound to food proteins is released in the stomach by pepsin and acid pH and more free cobalamin binds to HC than to IF. The cobalamin-HC complex moves to the intestinal lumen, is digested by pancreatic proteases, and the liberated cobalamin now complexes with IF. The cobalamin-IF complex moves through the small intestine and binds to a transmembrane receptor (IFCR) in the ileum. After endocytosis of the complex, cobalamin is released intracellularly and transferred to transcobalamin II (TC II). This cobalamin-TC II complex leaves the ileal mucosal cell and enters the circulation.
Vitamin B12
Published in Judy A. Driskell, Ira Wolinsky, Sports Nutrition, 2005
The most common biochemical indicator of B12 status is the demonstration of low serum or plasma cobalamin concentrations, which are usually associated with decreased tissue content of the vitamin. The lower levels of the normal range are about 200–250 pg/mL.8 Serum B12 levels can be determined by microbiological or radioisotope dilution assay. Although the latter procedures are used most often and are generally quite accurate, the presence of haptocorrins (transcobalamin analogues) in the plasma can sometimes obfuscate the binding of cobalamin,7 leading to erroneous interpretations. For example, B12 that is bound to haptocorrin is not available for cellular uptake, so subjects can have “normal” serum B12 levels and still be deficient in available B12 when there is an abnormally high level of B12 bound to haptocorrin.
Vitamin B12, homocysteine, and folic acid in patients suffering from bipolar disorders: Relationship with suicide
Published in The World Journal of Biological Psychiatry, 2023
Paola Mangiapane, Manuel Glauco Carbone, Alessandro Arone, Lucia Massa, Stefania Palermo, Walter Flamini, Elisabetta Parra, Benedetto Morana, Florinda Morana, Giovanni Bertini, Donatella Marazziti
Vitamin B12, also known as cobalamin, is a group-B vitamin regulating a variety of functions and requires dietary intake, as the human body cannot synthesise it (Watanabe and Bito 2018). Its sources include meat, eggs, legumes, some cheeses and others that influence its bioavailability (Allen 2010; Doets et al. 2013). Once ingested, B12 is released from animal proteins through the action of gastric factors, such as HCl and pepsin, and it is bound to a protein known as haptocorrin that is then destroyed in the intestine, thus allowing B12 to bind to a key glycoprotein, the intrinsic factor (IF) (Nielsen et al. 2012). The next step is the bonding of the B12-IF complex to the cubulin receptor in the ileum and then B12 gets transported to the plasma (Nielsen et al. 2012), where it is bound to transcobalamin and, to a greater extent, to haptocorrin, being then driven to cells or, alternatively, being stored in the liver (Carmel 2008; Stabler 2013; Miller and Green 2014).
Pediatric fibrolamellar hepatocellular carcinoma: case report and review of the literature
Published in Acta Chirurgica Belgica, 2021
Laura Depauw, Glenn De Weerdt, Ben Gys, Sofie Demeulenaere, Wouter Mebis, Dirk Ysebaert
Tumor markers are not very useful in diagnosing FL-HCC. AFP, the conventional marker for HCC, is not or unremarkably elevated in most FL-HCC cases [22]. Darcy et al. [7] reported elevated AFP (>20 ng/ml) in only 2.3% of their cases. Other authors have suggested neurotensin as a biomarker, though it has not been proven sensitive or specific enough to be a diagnostic marker [23,24]. Also, higher levels of serum vitamin B12 and unsaturated B12 binding capacities in FL-HCC, caused by the hepatoma B12-binding protein Haptocorrin, have been said to be associated with FL-HCC development [3,25,26]. Lildballe et al. monitored a 15-year-old boy diagnosed with FL-HCC, and found that there was an increased vitamin B12 and Haptocorrin at time of diagnosis, which normalised to values within the reference interval after tumor resection [26]. In this case report, the vitamin B12 and Haptocorrin levels were not measured at the time of diagnosis. A specific biomarker for FL-HCC is currently not available yet.
Vitamin B12 and its binding proteins in patients with non-small cell lung cancer referred to fast-track diagnostic work-up for lung cancer
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2020
Taj Lo-Bisgaard, Ulrick Espelund, Jan Frystyk, Torben Riis Rasmussen, Ebba Nexo, Johan Frederik Håkonsen Arendt
Circulating cobalamin is bound to transcobalamin or haptocorrin. Cobalamin-saturated transcobalamin, also known as holotranscobalamin, is responsible for delivering cobalamin to all tissues, while the function of haptocorrin remains to be clarified [6]. Curiously, haptocorrin is also present in various body fluids, including pulmonary secretions and intracellularly in leucocytes, which appear to contain very high concentrations [7]. Alterations in plasma cobalamin levels are caused by either increased concentration and/or saturation of transcobalamin and/or haptocorrin. Notably, an increased concentration of haptocorrin, and thereby also cobalamin, has been related to malignant conditions such as hematological malignancies and certain types of liver tumors [8]. Increased concentrations of total transcobalamin have been associated to macrophage activation [9,10].