Pseudovitamin B12

Pseudovitamin B₁₂ is a coordination complex of cobalt, which occupies the center of a corrin ligand and is further bound to an adenosine-containing sidechain. The sixth ("upper") ligand for the metal is alternatively cyano, methyl, hydroxo, or a second adenosyl group.^[4][5] All these analogs are biologically inactive in humans.^[1]

Compared to cobalamin (vitamin B₁₂), pseudovitamin B₁₂ has the "lower" ligand, 5,6-dimethylbenzimidazole (DMB), replaced with adenine.^[6]

Most cyanobacteria, including Spirulina, and some algae, such as Porphyra tenera (used to make a dried seaweed food called nori in Japan), have been found to contain mostly pseudovitamin B₁₂ instead of biologically active B₁₂.^[3][7] These pseudo-vitamin compounds can be found in some types of shellfish,^[1] in edible insects,^[8] and at times as metabolic breakdown products of cyanocobalamin added to dietary supplements and fortified foods.^[2][9]

Pseudovitamin B₁₂ can act as a coenzyme in a similar way to normal vitamin B₁₂ when a microbiological assay with Lactobacillus delbrueckii subsp. lactis is used, as that bacteria can utilize the pseudovitamin despite it being unavailable to humans. To get a reliable reading of B₁₂ content, more advanced techniques are available. One such technique involves pre-separation by silica gel and then assessment with B₁₂-dependent E. coli bacteria.^[1]

Pseudovitamin B₁₂ is the main corrin cofactor produced by Clostridium cochlearium,^[4] Limosilactobacillus reuteri, and the methanogenic methanococcales and Methanoplanus^[10] under anaerobic conditions, and by the cyanobacteria Nostoc commune and Aphanizomenon flos-aquae.^[11][12]

Despite production of this compound in groups as distantly related as lactic acid bacteria^[13] and cyanobacteria, DMB is preferred over adenine by the vast majority of versions of CobT, the enzyme responsible for making the active phosphoribosylated lower sidechain of cobalamin.^[6]

Salmonella enterica is able to make either B₁₂ or pseudovitamin B₁₂ depending on the availability of DMB. Its enzymes prefer DMB, but it remains able to grow when DMB is unavailable and pseudo-B₁₂ has to be made instead.^[11]

In organisms that produce pseudovitamin B₁₂, it takes the same role as vitamin B₁₂ does in humans: as a corrin cofactor that facilitates the function of enzymes.^[11] Pseudovitamin B₁₂ is also functional in some non-corrin-producing relatives of organisms that produce pseudovitamin B₁₂. This includes Lactobacillus delbrueckii subsp. lactis (LLD), which is in the same family as Limosilactobacillus reuteri.^[1] LLD is also able to use factor S and factor A (see § Other human-inactive cobamides below).^[14]

Cobalamide-dependent growth behavior of Sinorhizobium meliloti largely correlates with the cofactor binding selectivity of its methylmalonyl-CoA mutase (MCM). Among adenyl-cobamides, paseudovitamin B₁₂ does not bind to its MCM, factor A (see below) does slightly, and vitamin B₁₂ binds well.^[15]

Human apo-methionine synthase (MS) is able to be activated by methyl-pseudovitamin B₁₂ in vitro (in solution). Apo-MS is extremely unselective of cofactors: It is activated by all tested cobamides (vitamin B₁₂). It appears to only require the central cobalt atom to have an oxidation state of +2.^[16] Hydroxo-pseudovitamin B₁₂ is able to activate the MS in COS-7 cells, but unlike hydroxo-vitamin B₁₂, it does not increase the translation of MS (hydroxo-B₁₂ achieves this by binding to the internal ribosome entry site of MS mRNA).^[5]

Human methylmalonyl-CoA mutase (MCM) normally relies on the adenosyl form of vitamin B₁₂. It binds and works with some vitamin B₁₂ analogs in vitro (in solution), but not purinyl ones such as pseudovitamin B₁₂.^[17] Adenyl-pseudovitamin B₁₂ does not function as a cofactor or inhibitor of MCM in COS-7 cells.^[5]