Metabolism of Folic Acid and Vitamin B12 Flashcards
(a) What are the active forms of Vitamin B12 in the body?
(b) Other forms of Vitamin B12 such as ____________ and ____________ can be converted to these active forms within the body, ensuring that the body has sufficient active Vitamin B12 to support critical physiological functions.
(a) methylcobalamin and adenosylcobalamine]
(b) hydroxycobalamin, cyanocobalamin
What are food sources rich in Vitamin B12?
Liver, Kidney, Muscle, Egg, Dairy Products, Seafood
[fruits and vegetables are not a reliable source]
Vitamin B12 is primarily stored in the liver. In which form is it stored?
adenosylcobalamin
Discuss Vitamin B12 absorption.
📝 In the stomach, hydrochloric acid and pepsin help release vitamin B12 from the proteins in food.
📝 Free vitamin B12 binds to a glycoprotein called R-protein [also known as haptocorrin or transcobalamin I], which is secreted by the salivary glands and gastric mucosa.
📝 The vitamin B12-R-protein complex travels to the duodenum. Here, pancreatic enzymes degrade the R-protein, releasing free vitamin B12.
📝 Free vitamin B12 then binds to intrinsic factor, a glycoprotein produced by the parietal cells of the stomach.
📝 The complex travels to the ileum, the final part of the small intestine. Here, it is absorbed into the enterocytes via receptor-mediated endocytosis.
📝 Inside the enterocytes, vitamin B12 is released from intrinsic factor and binds to another protein called transcobalamin II.
📝 The vitamin B12-transcobalamin II complex enters the bloodstream and is transported to various tissues and organs, including the liver, where it is stored.
[Diagram 1] [Diagram 2]
Outline functions of Vitamin B12.
(1) Red blood cell formation
Vitamin B12 plays a role in the maturation of red blood cells in the bone marrow.
(2) DNA synthesis
It acts as a cofactor for the enzyme methionine synthase, which is involved in the conversion of homocysteine to methionine. Methionine is necessary for the formation of S-adenosymethionine (SAM), a universal methyl donor required for DNA methylation.
(3) Nervous system health
Vitamin B12 is vital for maintaining the health of the nervous system. It is involved in the synthesis of myelin.
(4) Energy production
Cobalamin plays a role in the metabolism of fatty acids and amino acids. It is a cofactor for the enzyme L-methylmalonyl-CoA mutase, which converts L-methylalonyl-CoA to succinyl-CoA, a critical step in the production of energy from fats and proteins.
(5) Homocysteine metabolism
By converting homocysteine to methionine, vitamin B12 helps regulate homocysteine levels in the blood. Elevated homocysteine levels are associated with an increased risk of cardiovascular diseases.
(6) Brain function and Mental health
Adequate levels of vitamin B12 are essential for cognitive function and mental health. Deficiency in cobalamin has been linked to memory loss, depression, and other cognitive impairments.
List causes of Vitamin B12 deficiency.
(1) Dietary insufficiency e.g. complete vegeterianism.
(2) Malabsorption issues
(i) pernicious anaemia, (ii) atrophic gastritis, (iii) gastrointestinal disorders e.g. Crohn’s disease, celiac disease, and bacterial overgrowth
(iii) surgical procedures that remove parts of the stomach or small intestine e.g. gastric bypass surgery
(3) Medications
Discuss symptoms of vitamin B12 deficiency.
atrophic glossitis, shuffling broad gait, anemia, vaginal atrophy, malabsorption, jaundice, personality changes, hyperhomocysteinemia, neurologic symptoms [e.g. numbness and tingling in hands and feet, difficulty walking, memory loss and cognitive difficulties, mood changes]
What are some folate rich foods?
green leafy vegetables, liver, kidney
Briefly discuss the absorption of folate/folic acid.
🩸 Naturally occuring folates are typically in the form of polyglutamates. These are hydrolysed to monoglutamates by enzymes in the small intestine before absorption. The synthetic form, folic acid, is already in the monoglutamate form and does not require hydrolysis.
🩸 Folate is primarily absorbed in the jejunum of the small intestine through an active transport mechanism involving specific folate transporters. [When pharmacological doses of folic acid are consumed, some absorption can occur through passive diffusion.]
🩸 Once inside the enterocytes, folate is reduced to dihydrofolate and then to tetrahydrofolate. THF is further converted to 5-methyltetrahydrofolate, the primary active form of folate in the plasma.
[Diagram 1] [Diagram 2] [Diagram 3]
Where is folate primarily stored and in what form is it stored?
liver, 5-MTHF
List functions of folate.
(1) DNA and RNA synthesis: Essential for genetic material creation and repair.
(2) Red blood cell formation: Prevents anemia by aiding in red blood cell production.
(3) Amino acid metabolism: converts homocysteine to methionine
(4) Neural tube development: During early pregnancy, folate is crucial for the proper development of the neural tube, which becomes the brain and spinal cord.
(5) Cell growth and function: supports overall tissue and cell health
(6) Mental health: some studies suggest that folate may play a role in mental health, potentially helping to reduce the risk of depression.
Briefly discuss folate deficiency symptoms.
(a) Fatigue, paleness and shortness of breath: common symptoms due to reduced red blood cell production, leading
(b) Oral symptoms: mouth sores, swollen tongue, reduced sense of taste
(c) Neurological symptoms: memory loss, difficulty concentrating, confusion
(d) Neural tube defects: in pregnant women, folate deficiency can lead to severe birth defects such as spina bifida and anencephaly
Discuss some effects of folate excess.
(1) Folate excess may mask vitamin B12 deficiency, which can delay diagnosis and treatment. This is particularly concerning because untreated B12 deficiency can lead to irreversible neurological damage.
(2) Increased cancer risks
What is the “methyl-folate” trap?
Vitamin B12 and folate are interdependent. Without vitamin B12, folate becomes trapped in its inactive form (5-methyl tetrahydrofolate), preventing it from participating in DNA synthesis. This “methyl-folate trap” leads to a functional folate deficiency even if folate levels are adequate.
