Role of Vitamin B12 in the Synthesis of Iron-Sulphur Proteins

Production of iron-sulphur proteins involves the movement of the sulphur atom from methionine into the sulphation pathway, via the enzyme cystathionine beta synthase. The activity of cystathionine beta synthase requires stimulation by high levels of S-Adenosylmethionine. Maintenance of S-Adenosylmethionine levels is dependent upon the methylation cycle, and more specifically of methyl-Co(III)cobalamin. Urinary Organic Acids Test data has been used to compare markers of functional vitamin B12 deficiency, with levels of the functional markers of aconitase deficiency (citrate) and succinate dehydrogenase deficiency (succinate). Studies reported here have shown for the first time that the activity of two iron-sulphur proteins, aconitase and succinate dehydrogenase are dramatically reduced in functional vitamin B12 deficiency. Such reduction is accompanied by increased secretion of succinic acid, aconitic acid and pyroglutamate. These studies have profound implications for understanding the processes involved in the development of diseases such as dementia, Parkinson’s Disease, and autism, each of which is associated with the vitamin B12 deficiency marker, homocysteine.