Hydroxycobalamin: Function & Diseases

Hydroxycobalamin is one of the naturally occurring substances in the vitamin B12 complex. It can be converted into the bioactive adenosylcobalamin (coenzyme B12) relatively easily by the body’s metabolism through a few steps. Hydroxycobalamin is more suitable than any other compound from the B12 complex for replenishing B12 stores in the body. It performs functions in blood formation and cell division and is considered a detoxifier in hydrogen cyanide (HCN) poisoning.

What is hydroxycobalamin?

Hydroxycobalamin (vitamin B12b), also known as hydroxocobalamin, is one of the biologically inactive forms of coenzyme B12 that can be converted by body metabolism via cyanocobalamin to the biochemically active adenosylcobalamin (coenzyme B12). Cyanocobalamin – although also biochemically inactive – is referred to as the actual vitamin B12. Hydroxycobalamin, which occurs naturally in many foods – especially animal foods – is well suited for storage in the body. The chemical molecular formula C62H89CoN13O15P reveals a central cobalt atom, or cobalt ion, with a one- to threefold positive charge in the complex structure. Cobalamins are the only known natural products with a built-in central cobalt ion, which is characteristic of all cobalamins. Hydroxycobalamin cannot be synthesized by the body’s own metabolism, but is ingested with food. As an acetate, the organometallic compound hydrocobalamin forms deep red, odorless crystal-like needles or platelets that are moderately soluble in water (20 g/l). The melting point is over 300 degrees Celsius.

Function, action and tasks

The overriding functions that bioactive coenzyme B12 (adenosylcobalamin) performs in human metabolism is its participation as a coenzyme in methionine metabolism. It serves in methionine synthase to regenerate S-adenosylmethionine (SAM) and to form methionine by remethylation of harmful homocysteine. The second important function of coenzyme B12 is its participation in the function of the enzyme methylmalonyl-CoA mutase (MCM). MCM has a central role in the metabolism of some amino acids, fatty acids and certain cholesterols. Its functions play a special role in the necessary replication or synthesis of DNA and RNA strands during cell division and have effects on erythrocyte formation (red blood cells) and in the formation of nerve tissue. Hydroxycobalamin, even in its unmodified form, has specific functions that other bioactive cobalamins do not have. These are its extraordinarily good depot function and its abilities to take over cyanide groups. The substance therefore has a detoxifying effect in cases of hydrogen cyanide poisoning, smoke poisoning and is effective in detoxifying the body during smoking cessation. In addition, hydroxycobalanin acts as an effective scavenger of NO radicals. This is a special form of oxidative stress and is referred to as nitrosative stress. Hydroxycobalamin is able to render NO radicals harmless. Unlike nitric oxide (NO), which performs important physiological functions as a neurotransmitter, NO radicals and the peroxinitrite formed from degradation products are harmful.

Formation, occurrence, properties, and optimal levels

Hydroxycobalamin is synthesized exclusively by a variety of microbes, mainly bacteria. Most microbes capable of synthesizing vitamin B12b are found as symbionts in the forestomachs of ruminants or in the large intestines of other herbivores, so that in the latter, vitamin B12 supply is ensured by symbiosis with the producing bacteria. A small percentage of cobalamin-producing bacteria in the large intestine of humans, as well as in omnivores and carnivores, shows no influence on the supply of hydroxycobalamin, because hydroxycobalamin can only be absorbed in the small intestine, i.e. the intestinal section before the large intestine, and is therefore excreted unused. Relevant amounts of absorbable vitamin B12b are found primarily in meat products, especially in fish and offal (e.g. liver). Smaller amounts are still found in milk and dairy products. Plant foods contain almost no hydroxycobalamin, except in lactic acid fermented products such as sauerkraut and in some legumes. The biological half-life of cobalamin in the body is 450 to 750 days.The vitamin is constantly released into the small intestine with bile acid, but is largely reabsorbed in the terminal ileum with the help of intrinsic factor. The total requirement of an adult is therefore only about 2.5 to 3 µg/day. With replenished vitamin B12 stores, a deficiency can be compensated for by the body over several years, so that symptoms of a deficiency may not become apparent until very late in some cases.

Diseases and disorders

A deficiency of cobalamin affects many metabolic processes. The main symptoms of vitamin B12 deficiency are seen in anemia, anemia, and neurological problems. Basically, a deficiency of vitamin B12 can develop due to a long-term undersupply, as can occur in vegans who completely abstain from eating animal products. More commonly than an undersupply of the vitamin, a deficiency occurs due to impaired absorption in the small intestine. A well-known autoimmune disease, pernicious anemia, is caused by gradual destruction of the parietal cells in the gastric mucosa that synthesize a specific protein, intrinsic factor, in the protection of which hydroxycobalamin survives intestinal passage undigested to be absorbed in the terminal ileum. Other factors that lead to decreased absorption of the vitamin include side effects of gastric acid inhibiting drugs and the use of nitrous oxide as an anesthetic. On the other hand, with a normal supply and normal absorption, deficiency can be caused by an increased requirement, which can occur, for example, in chronic stress situations, in nicotine abuse, and also in excessive alcohol consumption.