Coenzyme function
Methylcobalamin and adenosylcobalamin, as coenzyme forms of vitamin B12, are involved in three cobalamin-dependent metabolic reactions. Adenosylcobalamin acts in the mitochondria (power plants of cells). Mitochondria are responsible for energy production as part of cellular respiration and are found particularly in cells with high energy consumption, such as muscle, nerve, sensory and oocytes.Methylcobalamin exerts its effects in the cytosol, in the clear, liquid and slightly viscous portion of the cytoplasm. Adenosylcobalamin – intramolecular rearrangement of alkyl residues 5-deoxyadenosylcobalamin serves as a cofactor of methylmalonyl-CoA mutase. This enzyme is essential for the conversion of methylmalonyl-CoA to succinyl-CoA during the degradation of propionic acid in mitochondria. As a result of the rearrangement to succinyl-CoA, propionic acid generated during the degradation of odd-numbered fatty acids and branched-chain amino acids-isoleucine, leucine, and valine-as well as threonine and methionine can be introduced into the citrate cycle. Furthermore, adenosylcobalamin is required by leucine mutase as a cofactor and is thus involved in the reversible conversion of the amino acid leucine to 3-aminoisocaproic acid. The rearrangement to 3-aminoisocapronate (beta-leucine) initiates leucine degradation. Methylcobalamin – homocysteine methyl transferase reaction Methylcobalamin is a cofactor of methionine synthase and thus plays an essential role in the formation of methionine from homocysteine (homocysteine methyl transferase reaction). The vitamin is responsible for the transfer of methyl groups from methyltetrahydrofolic acid to homocysteine, with 5-methyltetrahydrofolic acid being the actual methyl group donor – synergy between vitamin B12 and folic acid. Remethylation of homocysteine leads to both synthesis of methionine and regeneration of metabolically active tetrahydrofolic acid (THF). THF is the biologically active form of folic acid and is a prerequisite for the synthesis of folate polyglutamate compounds, which are responsible for intracellular folate storage. By acting in the form of a coenzyme as a transmitter of active one-carbon compounds (C1 units, such as methyl, hydroxymethyl or formyl groups), THF regulates – especially in protein and nucleic acid metabolism – purine and pyrimidine synthesis, DNA synthesis, and the formation and degradation of various amino acids. Methionine is one of the essential amino acids and, as S-adenosylmethionine (SAM), which is formed by the reaction of methionine with ATP, is involved in a large number of metabolic processes. S-adenosylmethionine is a precursor in cysteine biosynthesis. In addition, it plays an important role in methyl group transfer as a key compound. S-adenosylmethionine provides a methyl group for certain methylation reactions, such as ethanolamine to choline, noradrenaline to epinephrine, or phosphatidylethanolamine to lecithin. In such methylations, homocysteine is always formed as an intermediate product, which must be remethylated with the help of methylcobalamin as a cofactor. Vitamin B12 deficiency impairs methionine as well as THF synthesis. The reduced formation of tetrahydrofolic acid results in a low synthesis of the storable folate polyglutamate compounds, which leads to a decrease in the folate concentration in all tissue cells including erythrocytes (red blood cells) in favor of serum folic acid. In addition, a deficit of cobalamin due to reduced degradation or remethylation leads to elevated homocysteine levels, which are a recognized risk factor for cardiovascular health. The focus is on the involvement of elevated plasma concentrations of homocysteine in the pathogenesis of atherosclerosis (arteriosclerosis, hardening of the arteries).
