The metabolic processes of folic acid and Vitamin B12 deficiency Mahmood L - J Health Res Rev
Folate and B12 are both involved in the conversion of homocysteine to Along with their sidekick, vitamin C) they help with the break down, creation, and use. Explains how the vitamin B12 and folate tests are used, when Vitamin B12 and folate are primarily ordered to detect deficiencies and to help. Interaction between vitamin B status and serum folate in relation to seem to support the idea that the neuropsychiatric consequences of.
Hyperhomocysteinemia is another consequence of deficiencies of either folate or vitamin B 2. This effect is due, in part, to the requirement by MS for both folate and vitamin B S-adenosylmethionine also serves as the sole methyl donor for the central nervous system, which may explain associations between folate deficiency and vitamin B deficiency and cognitive impairment and mental illness 34.
One of the most devastating consequences of vitamin B deficiency is a classic neuropathy called combined degeneration of the spinal cord 5. The mechanism by which vitamin B deficiency leads to this fatal demyelinating illness is unknown, but its specific link to vitamin B deficiency, but not folate deficiency, may provide a clue to the causal pathway. Another unique consequence of vitamin B deficiency relates to its role in the isomerization of L-methylmalonyl—coenzyme A CoA to succinyl-CoA—a reaction that, unlike the remethylation of homocysteine, occurs in the mitochondria and does not involve folate.
Thus, vitamin B deficiency specifically results in increased methylmalonic acid MMA concentrations in both plasma and urine. Pernicious anemia and excessive intake of folic acid After studying malnourished pregnant women in India in the late s, Lucy Wills described a macrocytic anemia that shared some features with the blood abnormalities of elderly Europeans with pernicious anemia 6. For example, the cytologic properties of the 2 anemias were identical, and both types responded well to crude liver extract.
However, only the tropical illness responded to yeast extract. Furthermore, although purified liver extract had proved effective in the treatment of pernicious anemia, it did not cure the tropical form 6. This hypothesis was subsequently verified.
However, the identification of vitamin B as the anti—pernicious anemia factor in liver 7 followed the isolation of folic acid from yeast 8 by several years, during which time folic acid was administered in large doses to patients with pernicious anemia 9. Because the inappropriateness of this treatment quickly became apparent, reports of cases thus treated in the late s and early s comprise the entire body of literature on the effect of folic acid administration on persons deficient for vitamin B 10 — Reviews of the historic case reports allude to rapid neurologic deterioration after improvement of anemia 10 Consequently, the idea has developed that excessive intake of folic acid can obscure or mask vitamin B deficiency and potentially delay its diagnosis until neurologic consequences become irreversible Food folic acid fortification and the debate on folic acid safety The move by the United States and other governments to fortify staple food products with folic acid for the prevention of neural tube defects rekindled the debate over the safety of folic acid for the elderly, who are at high risk of vitamin B deficiency.
The high degree of uncertainty led some to question the safety of fortification 1920 and inspired others to criticize the upper intake as too conservative 21 Particularly in light of continued demands for a higher level of fortification 2324clearly defining the benefits and risks of high folic acid intake assumes vital importance. Writing about this challenge, Moore 25 observed that the current fortification program provides the perfect opportunity for epidemiologic study of the unanswered questions, including those related to the interaction between folate and vitamin B Folate status and intake in the era of folic acid fortification Mandatory folic acid fortification of enriched cereal grain products sold in the United States officially took effect in January Both serine and glycine are transported across the mitochondrial membrane rapidly.
Also, many processes inside the body are impaired, such as impaired function of RNA and DNA, fat and fatty acid metabolism, and muscle formation. Low level of either serotonin or tryptophan has been linked to depression, confusion, insomnia, and anxiety.
Vitamin B12 And Folic Acid | Dr. Schweikart
Moreover, low serine level leads to decreased performance of the immune system since serine is involved in antibody formation. It is involved as 5-methyl tetrahydrofolate methionine in the methylation process where the methyl group is transferred to homocysteine to form methionine in the presence of methionine synthase enzyme. Methionine synthase is one of the only two enzymes known to be Bdependent enzymes. This process depends on both folic acid as well as vitamin B This reaction needs ATP and vitamin B12 and also the presence of methionine adenosyl transferase [Figure 1].
Methionine is also known to be essential for the formation of collagen that is involved in the formation of skin, nails, and connective tissues, and low methionine level has negative effects in these processes and functions.
Thymidylate synthase is involved in catalyzing the transfer of formaldehyde from folate to dUMP in order to form dTMP. Thymidylate synthase It is an enzyme that plays a role in the replication of cells and tissues. From this cycle, the role of folate can be linked to cancer. Thymidylate synthase is a metabolic poison that is involved in causing functional folate deficiency, and body's cells grow rapidly as a result of increase in DNA synthesis.
Many anti-cancer drugs act indirectly by inhibiting DHFR or directly by inhibiting thymidylate synthase. Purine has many important roles in cell growth, division, and development, since it is considered to be along with the pyrimidine base of the DNA helix. In case of folate deficiency, there is an impairment of functions of purine, which means impairment in production of DNA, and leads to many problems inside the body, since DNA is the basis of every process.
DNA defects affect each part of the body, i. Megaloblastic anemia is described as presence of large-sized red blood cells than normal. It results from the inhibition of DNA synthesis within red blood cell production. Since DNA synthesis becomes impaired, the cell cycle cannot progress and cell continues to grow without division, which presents as macrocytosis.
It can be a result of vitamin B12 deficiency and also due to trapping folate, preventing it from doing its normal function. This defect is caused by thymidylate synthesis defective with deoxyuridine triphosphate enlargement. Megaloblastic anemia leads to impairment of RBC, painful tingling of the hands and feet, gastrointestinal problems e. Also, formyltetrahydrofolate synthetase, which is known as domain of C1 tetrahydrofolate synthetase gene, has been shown that it is linked to a high risk of having neural tube defect.
The most well-known type of this defect is "spina bifida," which can lead to many problems and issues, e. According to the spina bifida association, it can also lead to learning disabilities, gastrointestinal disorders, obesity, depression, urinary and bowel dysfunction, tendonitis, and allergies.
Vitamin B12 commonly known as cyanocobalamin is the most chemically complex of all the vitamins. The structure of vitamin B12 is based on a corrin ring, which is similar to the porphyrin ring found in heme, chlorophyll, and cytochrome and has two of the pyrrole rings directly bonded.
Cyanocobalamin cannot be made by plants or animals; bacteria and archaea are the only types of organisms that have the enzymes required for the synthesis of cyanocobalamin. Higher plants do not concentrate cyanocobalamin from the soil, and so are poor sources of the substance, as compared with animal tissues.
Vitamin B12 is naturally found in foods including meat especially liver and shellfisheggs, and milk products. Infants adequate intake months: The enzyme methionine synthase needs methylcobalamin as a cofactor. This enzyme is normally involved in the conversion of the amino acid homocysteine into methionine, while methionine, in turn, is required for DNA methylation.
What Is the Relationship Between Folate & Vitamin B12?
This conversion is an important step in the extraction of energy from proteins and fats. In addition, succinyl CoA is necessary for the production of hemoglobin which is the substance that carries oxygen in red blood cells.
In case of vitamin B12 deficiency, the body does not have the ability to produce methionine, which leads to many problems. Also, the body does not have the ability to produce S-adenosyl methionine which is known as "SAM" product. These impairments lead to many problems and issues. The body loses its ability to produce the TCA cycle intermediate, succinyl CoA, which will lead to an impairment of TCA cycle as there is reduced conversion of succinate to fumarate, malate, and to the end product of the cycle, which is responsible for providing small amount of energy before going to electron transport chain which is responsible of high energy production.
When the fatty acid is oxidized into propionyl CoA, the role of succinyl CoA appears which is known as succinyl CoA precursor, that is then converted to pyruvate and enters the gluconeogenesis cycle. The most common disease caused as a result of B12 deficiency is pernicious anemia. Pernicious anemia Pernicious anemia is a type of anemia with the term "anemia" that usually refers to a condition in which the blood has a lower than normal number of red blood cells.
Vitamin B12 And Folic Acid
In pernicious anemia, the body has no ability to make enough healthy red blood cells because it does not have enough vitamin B Without enough vitamin B12, the red blood cells do not divide normally and are too large, and they may have trouble getting out of the bone marrow.
Not having enough red blood cells to carry oxygen to the body may give a feel of being tired and weak.
Severe or long-lasting pernicious anemia can damage the heart, brain, and other organs in the body. Pernicious anemia can also cause other problems such as nerve damage, neurological problems such as memory lossand digestive tract problems.
People who have pernicious anemia also may be at higher risk for weakened bone strength and stomach cancer.