Vitamin B12 Deficiency: What are the consequences?

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Vitamin B12 : An essential part of energy production

The main powerhouses for energy production within  the cell are the mitochondria. Within the mitochondria, fatty acids, sugars and amino acids can be converted to energy in the form of ATP via the glycolysis, Krebs cycle and the Electron Transport Chain. . Whilst is it is generally accepted that the B group vitamins play an essential role in energy production, vitamin B12 has several unique roles to play. Through its interaction with the folate and methylation cycles, methylcobalamin contributes the methyl group that is essential for the production of creatine (2-(Methylguanidino)ethanoic acid). In the muscles creatine and creatine phosphate supply "instant" energy through the conversion of creatine phosphate to ATP. Carnitine, formed from the break-down of N-methyl-lysine is essential for transport of free fatty acids into the mitochondria for use in energy production. In addition, methylcobalamin, through its role in the production of S-AdenosylMethionine (SAM), also is essential for the production of the electron-shuffle molecule ubiquinone (CoQ10), and in methyl B12 deficiency CoQ10 levels decrease. Elevated levels of SAM are also required in order to turn on the enzyme cystathionine beta synthase, and to pull the sulphur, originally resident in methionine, through CBS to generate iron-sulphur complexes, and in reduced B12 levels the activity of Fe-S proteins can be observed to decrease. The activity of one of these, aconitase, is critical for energy movement around Krebs cycle and in reduced B12, aconitase activity is reduces. Reduced aconitase activity has been associated with reduced mini mental score estimations, and dementia. In the mitochondria, adenosylcobalamin serves as an essential co-factor in the enzyme methylmalonyl-Co mutase, which utilizes odd chain fatty acids and odd chain amino acids for energy production. A deficiency of adenosylcobalamin can in itself lead to alterations in mitochondrial morphology and function..

Deficiency in adenosylcobalamin leads to the accumulation of methylmalonic acid, which disrupts normal glucose and glutamic acid metabolism in the cell due to its inhibitory activity on the Krebs cycle and by inhibition of ATP synthase. Continued deficiency of adenosylcobalamin, with resultant reduction in energy output can lead to anorexia, lacrimation, alopecia, and eventual emaciation. In addition there is a build up of lesions in the liver and the development of optic neuropathies. Elevated MMA also results in the formation of faulty lipids for incorporation into the myelin sheath of nerves.

Several studies have also shown that mitochondrial function can be affected by the generation of reactive oxygen species (ROS), which can result from decreased levels of glutathione within the cells due to VB12 deficiency and also because vitamin B12 is known to be a scavenger of nitric oxide.

In summary vitamin B12 deficiency has a dramatic effect on energy levels within the cell due to decreased creatine phosphate, reduced fatty acid uptake into the mitochondria, the toxicity of methylmalonic acid and increased levels of ROS. .

Further Information on the role of vitamin B12 in energy production and mitochondria

http://www.ncbi.nlm.nih.gov/pubmed/6886087

http://www.ncbi.nlm.nih.gov/pubmed/16814759

http://www.ncbi.nlm.nih.gov/pubmed/19760748