Vitamin B12 {90000185} Record Keys Parent:[ ] Definition:Vitamin B12 Queue:[ ] Details Initialisation date:2021-06-30 Specification: cobalaminSource: [ ] Meta Information Structural Type:[ ] Functional Type:Vitamin Function:Neurodevelopment Notes: [ ]Shared Reference Notes [1.1] [#Dementia] - Low B-12 not only causes central nervous system (CNS) damage by decreasing availability of methyl groups, but also allows accumulation of homocysteine, which appears to be toxic to nerve cells and blocks N-methyl-dasparate receptors. - It is also important to remember that for B-12 by itself to be functional, it needs to be converted to glutathionyl cobalamin, which requires glutathione for its synthesis. Oxidative stress can tie up glutathione and contribute further to lack of B-12 function. [1.2] - Vitamin B12 deficiency at the brain level is associated with affective disorders, behavior changes, psychosis, cognitive impairment or decline, and #Dementia (including #Alzheimer’s disease and vascular #Dementia protection) - Treatment with vitamin B12 in rats with experimental #Autism improved impaired markers of this neurologic condition [#Covid-19] - Methylcobalamin has a significant affinity to bind to the active site of the nsp12 protein of SARS-CoV-2, Thus, vitamin B12 may inhibit the RNA‐dependent RNA polymerase activity of nsp12 responsible for the replication of the viral genome. - The neurologic complications of B12 deficiency occur at a later stage of depletion and was associated with severe symptoms of #Depression, suicidal behaviors, reduced cognition, mental #Fatigue, bad or depressed moods, mania, psychosis, and intense agitation - Bacterial vitamin B12 is synthesized by the gut-resident Propionibacterium Freudenreichii, Lactobacillus reuteri, L.coryniformis, L. plantarum, Bifidobacterium animalis, B. infantis, and B. longum, among others, to produce adenosylcobalamin. -resident bacteria in the colon produce cobalamin, which regulates gene expression in gut Bacteroidetes. - severe vitamin B12 deficiency can also be associated with increased risk and severity of infections, because this deficiency affects the functions of phagocytes, production of interferon, replication of viruses, and maturation of T lymphocytes. - some scientists claim that natural methylcobalamin and adenosylcobalamin forms may have greater vitamin B12 activity than the synthetic cyanocobalamin form [1.3] - B12 supplementation may boost the production of protective #Butyrate [#Parkinson’s Disease] - increased fatty acids metabolism, and decreased biosynthesis of preQ0 and vitamin B12, at prodromal and early α-synucleinopathy. [#Parkinson’s Disease] - Low serum B12 level is common in early PD and related to the neuropathy in PD patients [1.4] - The smallintestine a lso contains microbes, such as #Bacteroides and #Prevotella, that aid in the synthesis of micronutrients, like #Vitamin K2 and B12 [1.5] - Vitamin B12 is a cofactor for the enzyme methylmalonyl-CoA mutase (MCM), which converts succinyl-CoA to methylmalonate in the #Succinate-#Propionate pathway. - Limiting vitamin B12 levels can lead to an accumulation of #Succinate. [1.6] [#Bifidobacterium infantis, #Bifidobacterium longum, #Clostridioides difficile, #Kingella denitrificans, #Propionibacterium freudenreichii] - Vitamin B12 producer are > #Pseudomonas denitrificans, #Bacillus megaterium, and Propionibacterium freudenreichi, #Bacteroides fragilis, #Prevotella copri, #Clostridium difficile, #Faecalibacterium prausnitzii, #Ruminococcus lactaris, #Bifidobacterium animalis, B.infantis, B.longum, and #Fusobacterium varium - Vitamin B12 supplementation in humans increased the relative abundance of #Prevotella, but decreased the abundance of #Bacteroides - #Bacteroides, do not have a vitamin B12 biosynthesis capability. However, most of them possess vitamin-B12-dependent enzymes [#Escherichia coli] - vitamin B12 supplementation in mice significantly decreased #Parabacteroides and #Lactobacillus and increased E. coli and #Enterococcus abundances in a murine model of #Colitis - Vitamin B12, also known as cobalamin, is one of the largest and most complex vitamins. - The other forms of this vitamin include cyano-, methyl-, deoxyadenosyl-, and hydroxy-cobalamin - There are limited bacteria that can synthesize vitamin B12 in the human gut, and most of them use precorrin-2 as a precursor. - Approximately 20% of gut bacteria can produce vitamin B12, and more than 80% of gut bacteria require B12 for their metabolic reactions - reduction in cell differentiation and intestinal barrier in vitamin-B12-deficient rats. - in patients with a vitamin B12 deficiency, the villus becomes shorter with a reduced villus/crypt ratio than in the control group [1.7] [#Metabolic associated fatty liver disease] - #Betaine, #Choline, #Betaine, #Folate, and vitamin B12 deficiencies may promote DNA methylation, boosting hepatic #Triglyceride production. [1.8] [#Akkermansia muciniphila, #Bilophila wadsworthia] - B12 biosynthesis genes were very common in gut microbes including B. wadsworthia, A. muciniphila, and #Escherichia/#Shigella [#Akkermansia muciniphila] - B12 producing capability of A. muciniphila [#Obesity] - severe but not moderate B12 deficiency induced adiposity [#Obesity] - #Silymarin and resulted bacterial B12 improved the liver lipid metabolism via suppressing lipogenesis and enhancing fatty acid oxidation. [#High Fat Diet] - B12 supplementation could help alleviate the HFD-induced liver fat accumulation in both rats and germ-free mice - #Silymarin treatment was associated with B12 biosynthesis and increased concentration of fecal as well as plasma B12 > due to bacterial biosynthesis - lipid metabolism by #Silymarin-adapted microbiota mainly attributed to bacterial B12 biosynthesis. [1.9] [#Plant Microbiome] - 128 MAGs harbored the cobC gene that encodes a cobalamin (vitamin B12) biosynthetic protein. This gene was highly prevalent in MAGs that belong to the bacterial orders #Sphingomonadales (44.8%), #Rhizobiales (46.4%), and #Pseudomonadales (34.6%). - #Helicobacter pylori infection > structural damage in gastric mucosa caused by chronic HP infection could affect the absorption of vitamin B12 and #Iron, a deficit of which is associated with #Dementia. [1.11] - Metabolic rewiring of these pathways by vitamin B12 reduces cholinergic signalling by limiting the availability of free #Choline required by neurons to synthesize #Acetylcholine - vitamin B12-producing bacteria that colonize the intestine can modulate excitatory cholinergic signalling and behaviour in the host #Caenorhabditis elegans. - vitamin B12 reduces cholinergic signalling in the nervous system through rewiring of the #Methionine (Met)/#S-adenosylmethionine cycle in the intestine. [1.12] - B12 appears to increase #Propionate and #Butyrate production by the human gut microbiota while also serving as a coenzyme of methylmalonyl-CoA mutase to break down #Propionate. - Unlike #Curli, B12 does not affect α-syn aggregation (Figure S1) and modulates neurodegeneration downstream of α-syn by inducing the breakdown of #Propionate, which is a key activator of metabolic genes involved in fatty acid and amino acid metabolism and energy production. - Removing B12 or supplementing #Propionate in the diet could metabolically rescue neurodegeneration without reversing α-syn aggregation, indicating the possibility of treating neurodegenerative diseases by simply changing the level of certain metabolites. [1.13] - #Lachnospiraceae NK4A136 group can synthesize #Vitamin K, specific B vitamins such as #Folic acid and vitamin B12References Notes[ ]