scholarly journals Biological function of cobalamin: causes and effects of hypocobalaminemia at the molecular, cellular, tissue and organism level

2020 ◽  
Vol 74 ◽  
pp. 443-451
Author(s):  
Zuzanna Rzepka ◽  
Mateusz Maszczyk ◽  
Dorota Wrześniok

Cobalamin (vitamin B12) is a complex compound, which is classified as a water-soluble vitamin. Absorption of cobalamin in the gut and its transport to cells is a unique process, in which many proteins are involved. The loss of function of these proteins causes serious cell homeostasis disturbance, which may result in the dysfunction of many tissues and organs. Vitamin B12, a cofactor of methionine synthase, provides methylation process and nucleic acid synthesis. Cobalamin is also necessary for methylmalonyl-CoA mutase activity. The enzyme synthesizes succinyl-CoA, an intermediate in tricarboxylic acid cycle. Vitamin B12 deficiency is an important and current health problem. It may be caused by insufficient dietary intake, age, or disease-related malabsorption and genetic defects of mechanisms involved in the absorption, transport and metabolism of cobalamin. Hypocobalaminemia can also result from long-term pharmacotherapy with medicines: metformin, proton pump inhibitors (e.g. omeprazole) and H2-receptor antagonists (e.g. ranitidine). Significant clinical symptoms of cobalamin deficiency include hematological abnormalities, mainly megaloblastic anemia, as well as neurological disorders resulting from degeneration within the nervous system. Early diagnosis and starting treatment with vitamin B12 increase chances for a complete cure. Therefore, the diagnostically important symptom of hypocobalaminemia may be skin manifestations, mainly hyperpigmentations, but also premature graying of hair. The aim of this review article was to summarize the current state of knowledge on the biological function of cobalamin, as well as the causes and consequences of its deficiency at the molecular, cellular, tissue and organism level.

2019 ◽  
Vol 18 (3) ◽  
pp. 70-77
Author(s):  
M. A. Lunyakova ◽  
V. G. Demikhov ◽  
S. N. Dronova ◽  
Yu. Yu. Kalinina ◽  
O. N. Zhurina

Vitamin B12 (cobalamin) deficiency in infants exclusively breastfed is usually the result of its deficiency in the mothers (vegetarians or in the presence of unrecognized pernicious anemia or malabsorption syndrome). Cobalamin is crucial for the normal development of the nervous system, the production of erythrocytes and the synthesis of DNA. The classic manifestation of its deficiency is megaloblastic anemia and, in advanced cases, pancytopenia. However, infants often present neurological symptoms (fatigue, failure to thrive, regress of developmental skills, lethargy, motor disorders), as a consequence of inadequate myelination of the brain. Cobalamin treatment is effective in the most children, however, the neurological deficit varying degrees may persist. The long-term prognosis depends on overall duration of vitamin B12 deficiency and severity of symptoms. The article presents our own interesting clinical observations. Parents gave their permission for using personal data for clinical research and publications.


2015 ◽  
Vol 17 (4) ◽  
pp. 444-454 ◽  
Author(s):  
Emma L. Kurnat-Thoma ◽  
Faith Pangilinan ◽  
Amy M. Matteini ◽  
Bob Wong ◽  
Ginette A. Pepper ◽  
...  

Cobalamin (vitamin B12) deficiency is a subtle progressive clinical disorder, affecting nearly 1 in 5 individuals > 60 years old. This deficiency is produced by age-related decreases in nutrient absorption, medications that interfere with vitamin B12 absorption, and other comorbidities. Clinical heterogeneity confounds symptom detection for elderly adults, as deficiency sequelae range from mild fatigue and weakness to debilitating megaloblastic anemia and permanent neuropathic injury. A better understanding of genetic factors that contribute to cobalamin deficiency in the elderly would allow for targeted nursing care and preventive interventions. We tested for associations of common variants in genes involved in cobalamin transport and homeostasis with metabolic indicators of cobalamin deficiency (homocysteine and methylmalonic acid) as well as hematologic, neurologic, and functional performance features of cobalamin deficiency in 789 participants of the Women’s Health and Aging Studies. Although not significant when corrected for multiple testing, eight single nucleotide polymorphisms (SNPs) in two genes, transcobalamin II ( TCN2) and the transcobalamin II-receptor ( TCblR), were found to influence several clinical traits of cobalamin deficiency. The three most significant findings were the identified associations involving missense coding SNPs, namely, TCblR G220R (rs2336573) with serum cobalamin, TCN2 S348F (rs9621049) with homocysteine, and TCN2 P259R (rs1801198) with red blood cell mean corpuscular volume. These SNPs may modify the phenotype in older adults who are more likely to develop symptoms of vitamin B12 malabsorption.


Author(s):  
Vivek Kumar Verma ◽  
V. Vijayavarman

Cobalamin (Vitamin B12) is a water-soluble vitamin. Cobalamin is synthesized only by microorganisms. The only source of vitamin B12 for humans is food of animal origin. Hyperpigmentation of skin has been reported only rarely as the presenting manifestation of vitamin B12 deficiency. We report a patient who had hyperpigmentation as her presenting medical complaint and in whom Vitamin B12 deficiency was the cause.  A 36-year-old female presented with generalised weakness and progressive and asymptomatic hyperpigmentation of hand and feet for 5 months. She is vegetarian by diet. On examination, hyperpigmentation was present over dorsal aspect of metacarpophalangeal, proximal and distal interphalangeal joints. Hyperpigmentation were present over dorsum of the foot and over the joints. The tongue was depaillated, and hyperpigmentation was present. Her serum level of vitamin B12 was diminished (83pg/ml). Megaloblastic anemia presents with protean manifestations. The association between vitamin B12 deficiency and hyperpigmentation, although unusual, has been described. Cutaneous manifestations associated with B12 deficiency include characteristic mucocutaneous hyperpigmentation (most common), vitiligo, angular cheilitis, and hair-nail changes. It mainly affects knuckle pads and oral mucosa. It is an under-recognized sign of megaloblastic anemia and should always be looked for in the setting of pallor. Hyperpigmentation could be the earliest manifestation of vitamin B12 deficiency before anemia sets in. It is worthwhile to consider the possibility of vitamin B12 or folate deficiency in a patient with unexplained pigmentary changes. Early detection and adequate treatment will prevent anemia and various neurological manifestations.


2020 ◽  
Vol 90 (1-2) ◽  
pp. 151-155
Author(s):  
Khalid M. Al-Batayneh ◽  
Mazhar Salim Al Zoubi ◽  
Bahaa Al-Trad ◽  
Emad Hussein ◽  
Wesam Al Khateeb ◽  
...  

Abstract. Vitamin B12 (Cobalamin) deficiency, due to improper internalization of cobalamin, is a metabolic disorder prevalent in impoverished and elderly populations and is associated with megaloblastic anemia and dementia. It has been suggested that mutations in transcobalamin II ( TCN2) or gastric intrinsic factor (GIF) proteins can alter their binding efficiency to cobalamin or reduce the ability of their receptors to internalize them. In this case-control study, the correlation between vitamin B12 deficiency and alternative alleles of TCN2 and GIF was investigated in a Jordanian population. One hundred individuals with vitamin B12 deficiency (B12 < 200 mg/mL) were enrolled in our study to evaluate the TCN2 and GIF polymorphisms. The control group (B12 > 200 mg/mL) included 100 individuals. Our results indicated a significant association between the homologous variant of the TCN2 gene (G776G) and vitamin B12 deficiency, and an intermediate phenotype in heterozygous individuals ( p < 0.001, OR = 5.6, 95% CI = 2.95 to 10.63). The GIF gene, however, showed no correlation between the A68G variant and vitamin B12 deficiency ( p = 0.2). This study expounds the association of TCN2 polymorphism with cobalamin levels in a Jordanian population and highlights the necessity of further studies to elucidate the molecular basis and impact of TCN2 and GIF genes polymorphisms on vitamin B12 deficiency and associated disorders.


2019 ◽  
Vol 3 (1) ◽  
pp. 9-15
Author(s):  
Kanaparthi Alekhya ◽  
Srikar Muppirala

Vitamin B12, also known as cobalamin is a water soluble vitamin. It is critical for normal functioning of the red blood cell formation and nervous system. It is a complex vitamin and it’s deficiency is known to be one of the commonest deficiency in Indian population particularly in elderly and in vegans as it requires castles intrinsic factor released by parietal cells in the stomach for its absorption.  Vitamin B12 deficiency may also result from pernicious anemia, gastrectomy & intestinal malabsorption. It is often overlooked and may cause several oral, haematological, gastrointestinal, psychiatric and neurological manifestations. As it affects the oral mucosal tissues, early diagnosis of the manifestations may aid in diagnosing the underlying cause even before haematological examination. Hence, oral physicians should be vigilant enough to identify signs or symptoms of suspected vitamin deficiency in populations at risk. Early diagnosis is crucial for starting replacement therapy to avoid irreversible neurological damage. This article reviews the various oral manifestations of vitamin B12 deficiency and its management.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1913
Author(s):  
Alessandra Vincenti ◽  
Laura Bertuzzo ◽  
Antonio Limitone ◽  
Giuseppe D’Antona ◽  
Hellas Cena

Vitamin B12 (also known as cobalamin) is an essential water-soluble vitamin that plays a pivotal role for several physiologic functions during one’s lifespan. Only certain microorganisms are able to synthetize B12, thus humans obtain cobalamin exclusively from their diet, specifically from animal-derived foods. Specific sub-group populations are at risk of vitamin B12 subclinical deficiency due to different factors including poor intake of animal source foods and age-dependent decrease in the capacity of intestinal B12 uptake. Consumption of animal products produces some negative health issues and negatively impacts sustainability while a plant-based diet increases the risk of B12 deficiency. Taking a cue from the aforementioned considerations, this narrative review aims to summarize facts about B12 deficiency and the burden of inadequate dietary intake in elderly population, as well as to discuss sustainable approaches to vitamin B12 deficiency in aging population.


Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 987-1000 ◽  
Author(s):  
R Carmel ◽  
B Tatsis ◽  
L Baril

A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% of the endogenous vitamin B12 and was not found in his saliva, granulocytes, or urine. This protein was shown to be a complex of TC II and a circulating immunoglobulin (IgGkappa and IgGlambda). Each IgG molecule appeared to bind two TC II molecules. The reacting site did not interfere with the ability of TC II to bind vitamin B12, but did interfere with its ability to transfer the vitamin to cells in vitro. The site was not identical to that reacting with anti-human TC II antibody produced in rabbits. Because of this abnormal complex, 57Co-vitamin B12 injected intravenously was cleared slowly by the patient. However, no metabolic evidence for vitamin B12 deficiency was demonstrable, although the patient initially had megaloblastic anemia apparently due to folate deficiency. The course of the vitamin B12-binding abnormalities was followed over 4 yr and appeared to fluctuate with the status of the patient's illness. The IgG-TC II complex resembled one induced in some patients with pernicious anemia by intensive treatment with long-acting vitamin B12 preparations. The mechanism of induction of the antibody formation in our patient is unknown.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyan Chen ◽  
Rong Wang ◽  
Xusheng Huang ◽  
Fei Yang ◽  
Shengyuan Yu

Subacute combined degeneration (SCD) is a neurological complication of cobalamin deficiency, which is usually caused by chronic autoimmune atrophic gastritis. Serum pepsinogen 1 and the ratio of pepsinogen 1/pepsinogen 2 (PG1/2) can reflect the severity of gastric atrophy.Objective: This work aims to investigate whether decreased serum PG1 and PG1/2 ratio are helpful in diagnosing SCD and reflecting the severity of SCD.Methods: We retrospectively analyzed the clinical and laboratory tests of 65 cases of SCD due to vitamin B12 deficiency and compared the laboratory parameters of SCD with 65 age- and sex-matched amyotrophic lateral sclerosis (ALS) patients.Results: PG1 and PG1/2 ratio were decreased in 80 and 52.3% of SCD patients, respectively. Compared to patients with PG1/2 ratio ≥3.0, patients with PG1/2 ratio &lt;3.0 had more severe anemia, larger mean corpuscular volume (MCV), lower level of vitamin B12, higher folate and homocysteine (Hcy), more severe changes in somatosensory evoked potential (SEP), and higher rate of lesions in spinal MRI (P &lt; 0.05). PG1 and PG1/2 ratio had inverse correlation with MCV and N20 latency in SEP examination (P &lt; 0.05). PG1/2 ratio, RBC count, and Hcy were independent risk factors for SCD in logistic regression analyses. The ROC curve analysis revealed that the diagnostic accuracy of PG1 and PG1/2 ratio was 72.2 and 73.0%, respectively, while the cutoff values were 22.4 ng/ml and 2.43 for SCD, respectively.Conclusions: Decreased PG1 and PG1/2 ratio are helpful for the diagnosis and evaluation of the severity of SCD due to vitamin B12 deficiency.


2019 ◽  
Vol 59 (2) ◽  
pp. 40 ◽  
Author(s):  
Synara Cavalcante Lopes ◽  
Daniel Duarte Gadelha ◽  
Manuela Dias de Carvalho ◽  
Virgínia Oliveira Fernandes ◽  
Renan Magalhães Montenegro Junior

Vitamin B12 is a water-soluble essential micronutrient, required by all the body cells. Its deficiency has been implicated not only in hematological and neurological disorders, but also in many metabolic processes, such as insulin resistance and body composition changes, which have aroused particular interest in recent years. This study reviews the physiology of vitamin B12 from its digestion and absorption to its distribution in tissues, metabolic effects and controversies regarding the diagnosis of deficiency, and to dietary and pharmacological treatments.


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