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Questions and Answers
Which factor is primarily responsible for the regulation of erythropoiesis?
Which factor is primarily responsible for the regulation of erythropoiesis?
What role does erythropoietin play in erythropoiesis?
What role does erythropoietin play in erythropoiesis?
Which of the following is a clinical sign of Vitamin B₁₂ deficiency?
Which of the following is a clinical sign of Vitamin B₁₂ deficiency?
Which vitamin is essential for the production of DNA and the formation of red blood cells?
Which vitamin is essential for the production of DNA and the formation of red blood cells?
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What dietary source is rich in Vitamin B₁₂?
What dietary source is rich in Vitamin B₁₂?
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How does a deficiency in folic acid primarily affect the body?
How does a deficiency in folic acid primarily affect the body?
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What is the recommended daily intake of Vitamin B₁₂ for adults?
What is the recommended daily intake of Vitamin B₁₂ for adults?
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What is one of the key functions of folic acid in the body?
What is one of the key functions of folic acid in the body?
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What is the recommended dietary allowance (RDA) for folate during pregnancy?
What is the recommended dietary allowance (RDA) for folate during pregnancy?
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Which of the following is a biologically active coenzyme form of folic acid?
Which of the following is a biologically active coenzyme form of folic acid?
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Which statement about the absorption of folic acid is true?
Which statement about the absorption of folic acid is true?
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In which form is folate primarily found in the blood?
In which form is folate primarily found in the blood?
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What type of vitamin B₁₂ administration is required for life-long therapy?
What type of vitamin B₁₂ administration is required for life-long therapy?
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Which food is NOT a good source of folate?
Which food is NOT a good source of folate?
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What is the primary role of folic acid's active coenzyme forms?
What is the primary role of folic acid's active coenzyme forms?
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How is folic acid transported in the blood?
How is folic acid transported in the blood?
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What is a major cause of Vitamin B₁₂ deficiency related to the absorption process?
What is a major cause of Vitamin B₁₂ deficiency related to the absorption process?
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Which condition is primarily characterized by the inhibition of DNA synthesis during red blood cell production?
Which condition is primarily characterized by the inhibition of DNA synthesis during red blood cell production?
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Which of the following correctly describes the effect of high levels of folic acid in the presence of Vitamin B₁₂ deficiency?
Which of the following correctly describes the effect of high levels of folic acid in the presence of Vitamin B₁₂ deficiency?
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Which of the following conditions is directly associated with impaired uptake of Vitamin B₁₂ due to lack of intrinsic factor?
Which of the following conditions is directly associated with impaired uptake of Vitamin B₁₂ due to lack of intrinsic factor?
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What role does methylmalonyl CoA play in the pathology of neuropathy due to Vitamin B₁₂ deficiency?
What role does methylmalonyl CoA play in the pathology of neuropathy due to Vitamin B₁₂ deficiency?
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Which of the following is NOT typically a characteristic of megaloblastic anemia?
Which of the following is NOT typically a characteristic of megaloblastic anemia?
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Vitamin B₁₂ can be assessed through which of the following methods?
Vitamin B₁₂ can be assessed through which of the following methods?
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Which genetic condition is linked to a defect in the transport of Vitamin B₁₂?
Which genetic condition is linked to a defect in the transport of Vitamin B₁₂?
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Study Notes
Learning Objectives
- Discuss factors regulating erythropoiesis
- Discuss vitamin B12 and folic acid metabolism
- Describe biochemical functions, dietary sources, and recommended daily intake of vitamin B12 and folic acid
- Discuss clinical significance of vitamin B12 and folic acid deficiency
Erythropoiesis Regulation
- Tissue oxygenation is a primary regulator of red blood cell (RBC) production.
- Factors like low blood volume, low blood flow, low hemoglobin, anemia, and impaired oxygen absorption in pulmonary disease decrease tissue oxygenation.
- Erythropoietin (a glycoprotein), primarily from the kidneys (80-90%), and also from the liver and macrophages, stimulates pro-erythroblast production from hematopoietic stem cells, increasing RBC production.
Vitamin Classification
- Vitamins are categorized as water-soluble and fat-soluble.
- B-complex vitamins include thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid, biotin, vitamin B6 (pyridoxine, pyridoxal, pyridoxamine), vitamin B12, and folic acid.
- Fat-soluble vitamins include Vitamin A, D, E, and K.
Vitamin B12
- Role: Essential for RBC formation, cell metabolism, nerve function, and DNA production.
- Deficiency symptoms: Weak muscles, numbness, trouble walking, nausea, weight loss, irritability, fatigue, and increased heart rate.
- Function: Healthy red blood cell and marrow production, nervous system function, sperm production, strong immunity, improved mental energy and memory. Protects against toxins like cyanide (in cigarettes)
- Sources: Milk, eggs, liver, dairy products, fish, and shellfish.
- Prevention: Pernicious anemia, intestinal malabsorption
- Toxicity: Slight stomach upset
Forms of Vitamin B12
- Cyanocobalamin (commercial preparation)
- Hydroxycobalamin
- Adenosylcobalamin (major storage form in the liver)
- Methylcobalamin (mostly found in blood circulation)
Vitamin B12 Structure
- Consists of a nucleotide, a tetrapyrrole corrin ring, a cobalt ion, and an R-group.
- Different forms of vitamin B12 vary based on the R-group. (e.g., cyanide in cyanocobalamin, hydroxyl in hydroxycobalamin)
- Coenzyme forms of vitamin B12, such as adenosylcobalamin and methylcobalamin, have specific R groups (adenosyl and methyl).
Coenzyme Forms
- Adenosylcobalamin and methylcobalamin are coenzymes, essential for metabolic reactions.
Dietary Recommendations of Vitamin B12
- Recommended daily intake 2.4ugm/day for men and women.
Vitamin B12 in Metabolism
- Two crucial reactions require Vitamin B12 in the body
- Methylmalonyl CoA conversion through propionyl CoA and methylmalonyl CoA mutase.
- Causes methylmalonic aciduria: Methylmalonyl CoA is excreted in the urine, disrupting myelin fatty acid synthesis which causes nerve damage.
- Important for converting homocysteine to methionine, a process crucial for maintaining neurological function
- Tetrahydrofolate synthesis, which is also crucial for DNA synthesis and cell division.
Deficiency of Vitamin B12
- Deficiency leads to homocysteine accumulation, leading to neurological manifestations.
- Impedes the formation of purines and thymidine monophosphate, resulting in megaloblastic anemia (abnormal blood cell formation)
Folate
- The word folate is derived from the Latin word for "leaf," referring to its presence in leafy green vegetables and spinach.
- Folic acid comprises a pteridine ring, para-aminobenzoic acid (PABA), and glutamic acid residues.
- Stored mainly in the liver.
Biochemical Function of Folate
- The active coenzyme forms of folic acid are tetrahydrofolic acid (FH4), N5-methyltetrahydrofolic acid (N5-methyl-THF), and N10-formyltetrahydrofolate.
- Essential for various synthetic reactions involving one-carbon units.
Folate Requirements
- Folate requirements are adjusted for varying folate absorption efficiencies in dietary forms versus supplements.
- Adult needs: 400µg DFE
- Pregnant needs: 600 µg DFE
- Lactation needs: 500 µg DFE
Folate Absorption
- Readily absorbed in the jejunum.
- Transported by beta-globulins.
- Taken up by the liver, where coenzymes are produced.
Folate Tissue Distribution
- 50% of total body folate located in the liver.
- Rapid cell division tissues have high folate requirements.
Folate Functions and Mechanisms
- THF acts as a coenzyme in both mitochondria and cytoplasm for accepting one-carbon units generated from amino acid metabolism.
- Folate derivatives are key donors of one-carbon units for various synthetic reactions, including amino acid synthesis.
- Methyl groups accepted by THF bind to nitrogen positions 5 or 10 (or both).
Folate in Heme Synthesis
- Involved in converting methylmalonyl CoA to succinyl CoA.
- THF involved in other synthetic reactions.
Folic Acid Deficiency Causes
- Alcoholism
- Folic acid antagonists
- Oral contraceptives
- Low dietary intake (e.g., excessive goat milk)
- Infection with giardia
- Celiac Sprue
- Pregnancy and psoriasis
- Old age
- Dilantin (phenytoin)
Deficiency Symptoms
- Symptoms similar to vitamin B12 deficiency.
- Folate deficiency affects cellular processes by impairing DNA synthesis, specifically dTMP and purine synthesis.
- Megaloblastic anemia is the result.
- Pregnancy deficiency can cause neural tube defects.
- Deficiency during pregnancy.
Folate Deficiency Anemia Assessment
- Methylmalonic aciduria
- Serum folate level (normal is ~ 20ng/mL)
- Peripheral smear (macrocytic, hypochromic)
- Homocysteinuria
Vitamin B12 & Folate Deficiency Treatment
- Initiated with folic acid and vitamin B12 until the cause is determined.
- Therapy with Vitamin B12 is typically lifelong and can involve oral supplements or IM injections.
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Description
Explore the critical factors regulating erythropoiesis, including the role of tissue oxygenation and erythropoietin. Delve into the metabolism of vitamin B12 and folic acid, their dietary sources, recommended intakes, and the clinical effects of their deficiencies.
