Cobalamin (vitamin B12) is essential to human metabolism, and genetic diseases involving its absorption comprise an increasing portion of inherited newborn disease.

Production and absorption occur simultaneously, though certain factors can impede its production or interfere with absorption such as proton pump inhibitors and antacids that interfere with absorption.

Deficiency

B12 stands apart among vitamins in that it can only be produced by certain bacteria. As such, its production remains an evolutionary mystery due to requiring specific enzymes that have yet to be discovered in genome databases.

Cobalamin is required by two eukaryotic enzymes known as MS (methylene thiolate reductase) and MCM (methylmalonyl-CoA synthase). Prokaryotic organisms utilize numerous other enzymes requiring cobalamin, including methyltransferases such as d-lysine-5,6-aminomutase) and isomerases such as ribonucleotide reductase/diol dehydratase).

Biosynthesis of cobalamin takes place exclusively within bacteria and microorganisms; however, its transport through mammalian intestines to its final destination remains unknown. Thus far, little was understood regarding how cobalamin enters bloodstream and cells within body as it travels across intestinal mucosa to be absorbed.

Ulrich Kleinekathofer of Constructor University Bremen in Germany led a team of scientists who recently discovered how this is accomplished, publishing their findings in “Nature Communications” at the beginning of August.

To test their hypothesis, the researchers collaborated with students at a nearby school to grow garden cress seedlings in media with increasing concentrations of B12. After seven days they examined these seedlings and observed some taking up this nutrient into vacuoles within their cells to store.

To verify their findings, the team cloned the gene that encodes MMAA (methylene thiolate reductase). They identified more than 30 mutations found among cblA patients; most were chain-terminating frameshift mutants, suggesting MMAA may play a part in exporting molecules out of lysosomal compartment. Furthermore, even with such severe mutations present, most did not display symptoms associated with megaloblastic anemia or homocystinuria while responding well to supplementation with B12. Perhaps involvement of MMAA in uptake may help explain this phenomenon?

Treatment

The B complex comprises eight water-soluble vitamins: Thiamine (vitamin B1), Riboflavin (vitamin B2), Niacin (vitamin B3), Pantothenic Acid (vitamin B5), Pyridoxyine (vitamin B6), Biotin, and Vitamin B12. All eight water-soluble B vitamins play key but distinct roles within our bodies – unlike many other vitamins though, water-soluble B vitamins cannot be stored by the body so they must be replenished through diet or supplements regularly.

Scientists can diagnose pernicious anemia based on low levels of B12 in the blood, and treat it by administering an injection of B12. While this treatment helps correct anemia and make people feel more perky, memory issues associated with pernicious anemia still aren’t fully remedied by it. If large quantities of B12 production were to become feasible in future, an inexpensive pill that supplies sufficient levels could provide enough nutrient to correct memory issues caused by pernicious anemia.

Researchers from the University of Kent recently conducted a groundbreaking research project that demonstrated how it is possible to cultivate plants that can absorb and store cobalamin, normally only found in meat products. Together with students from local schools, researchers at UoK used common garden cress seedlings as test subjects while monitoring uptake with fluorescent B12 molecules.

Scientists can track the movement of molecules using this technique, hoping to use this approach to understand why certain people are more prone to B12 deficiency than others. Furthermore, this technique has shown that mutant proteins commonly seen in late-onset cblC patients don’t bind as strongly to CNCbl as OHCbl; an essential finding which may provide insight into its causes.

By integrating their technology into common crops that people eat already, the team hopes to make it easier for people to access enough B12, an essential nutrient required for neurological function, red blood cell formation and DNA synthesis. At present, people can only access sufficient B12 via meat-based foods or by receiving an injection of cyanocobalamin.

Prevention

UK scientists have developed an innovative solution for making plants produce and absorb vitamin B12, potentially revolutionising food production and human health. Prior to now, those following a plant-based diet had to supplement their intake through fortified food or supplements.

Research teams from the University of Kent and Sir Roger Manwood’s School in Sandwich, working alongside year 11 and 12 students, successfully produced common garden cress seedlings which absorbed cobalamin; then tracked its movement using fluorescent B12 molecules activated with laser light that emit light when activated allowing scientists to observe where it entered and stored in plant cells.

Vitamin B12 has long been recognized for its critical role, yet has proved an extremely difficult molecule to comprehend. Produced exclusively by bacteria and consisting of around 30 individual components, its structure remains complex despite our best efforts at understanding it. Unfortunately, until now it had not been possible to fully assemble this puzzle piece.

Ulrich Kleinekathofer and his colleagues at Constructor University of Bremen published in Nature Communications have at long last provided us with the answer as to how bacteria in our gut are able to take in vitamin B12. They identified proteins which act like lids on buckets; when vitamin B12 is nearby they open and take it in before closing again after taking in what they can from it.

By uncovering this ‘pedal-bin mechanism’, researchers gained a better understanding of how bacteria in the gut absorb vitamin B12. With this new knowledge in hand, the scientists began to comprehend why some individuals may be more prone to deficiency. Furthermore, this breakthrough could ultimately aid them in creating B12-enriched plants as a natural source for those following plant-based diets.

Diet

Vitamin B12 is essential for healthy blood cells that carry oxygen around the body while eliminating carbon dioxide, and its deficiency can lead to serious health conditions such as anemia and mental health issues, according to MedlinePlus. People deficient in this essential nutrient often feel tired, struggle breathing and have memory and mental health problems that impede recovery – getting adequate amounts in through food alone may not suffice, so supplements may provide additional help if absorption issues exist.

Traditional sources of this nutrient were animal sources such as liver and meat; however, as more individuals opt for plant-based diets for ethical or environmental reasons, vitamin B12 deficiency has seen an upsurge. Researchers are making strides towards solving this problem through biofortifying plants with essential vitamin content.

Team from John Innes Centre, LettUs Grow and Quadram Institute have discovered that certain plants can absorb and transport vitamin B12. Scientists were able to use an unusual strain of garden cress which was capable of taking in and storing cobalamin from its growth medium, then used special light tracking the movement of nutrients inside seedlings; this allowed them to confirm whether the nutrient had actually reached cells before being stored within vacuoles (Phys.org).

Scientists were able to observe that both folate and B12 presence had led to changes in DNA methylation patterns within cells, signalling that such modifications can be affected by nutritional factors beyond genetic mutations and diseases alone. This discovery demonstrated the power of nutrition as an influencer on DNA methylation patterns.

The findings of this research could have major ramifications for food production and global health. According to the team behind it, using B12 synthesis by plants for creating products more suited for vegetarian or vegan diets as well as supplements for those who experience difficulty digesting certain forms of protein could make an enormous difference to production costs and global wellbeing.