Podcast
Questions and Answers
Which of the following one-carbon units can FH4 carry?
Which of the following one-carbon units can FH4 carry?
- Methyl (CH3) (correct)
- Acetyl (C2H3)
- Hydroxymethyl (CH2OH)
- Formyl (CHO) (correct)
What is the consequence of folate deficiency in rapidly dividing cells?
What is the consequence of folate deficiency in rapidly dividing cells?
- Enhanced DNA synthesis
- Decreased red blood cell size
- Development of macrocytic, normochromic red blood cells (correct)
- Increase in cell division rate
Which reaction involves thymidylate synthase?
Which reaction involves thymidylate synthase?
- Conversion of dTMP to dUMP
- Transfer of one-carbon groups from serine
- Conversion of dUMP to dTMP (correct)
- Synthesis of purine rings
Which one-carbon donor is involved in the synthesis of purine rings?
Which one-carbon donor is involved in the synthesis of purine rings?
Which of the following represents a direct effect of folate deficiency?
Which of the following represents a direct effect of folate deficiency?
What role does Tetrahydrofolate (FH4) play in DNA synthesis?
What role does Tetrahydrofolate (FH4) play in DNA synthesis?
Which statement accurately describes the function of Vitamin B12 in one-carbon metabolism?
Which statement accurately describes the function of Vitamin B12 in one-carbon metabolism?
What is the significance of formyl-FH4 in human metabolism?
What is the significance of formyl-FH4 in human metabolism?
What is a primary consequence of Vitamin B12 deficiency?
What is a primary consequence of Vitamin B12 deficiency?
How does methotrexate influence one-carbon metabolism?
How does methotrexate influence one-carbon metabolism?
What is the primary role of S-adenosylmethionine (SAM) in metabolism?
What is the primary role of S-adenosylmethionine (SAM) in metabolism?
What enzyme converts folate to its active form Tetrahydrofolate (FH4)?
What enzyme converts folate to its active form Tetrahydrofolate (FH4)?
Which aspect of folate metabolism is crucial for preventing neural tube defects?
Which aspect of folate metabolism is crucial for preventing neural tube defects?
What is the role of vitamin B12 in the conversion of homocysteine to methionine?
What is the role of vitamin B12 in the conversion of homocysteine to methionine?
What happens to folate if CH3 cannot be removed from FH4-CH3?
What happens to folate if CH3 cannot be removed from FH4-CH3?
Which process is directly associated with S-adenosylmethionine (SAM)?
Which process is directly associated with S-adenosylmethionine (SAM)?
What is the consequence of B12 deficiency on folate metabolism?
What is the consequence of B12 deficiency on folate metabolism?
What are the health effects associated with functional folate deficiency due to B12 deficiency?
What are the health effects associated with functional folate deficiency due to B12 deficiency?
The methyl-trap hypothesis indicates that what occurs in the absence of adequate B12?
The methyl-trap hypothesis indicates that what occurs in the absence of adequate B12?
Which molecule donates methyl groups in most reactions requiring one-carbon units?
Which molecule donates methyl groups in most reactions requiring one-carbon units?
What could contribute to hyperhomocysteinemia?
What could contribute to hyperhomocysteinemia?
What is the primary target of the folate analog methotrexate?
What is the primary target of the folate analog methotrexate?
Which drug inhibits bacterial growth by affecting folate metabolism?
Which drug inhibits bacterial growth by affecting folate metabolism?
Both methotrexate and 5-fluorouracil lead to which type of cellular death?
Both methotrexate and 5-fluorouracil lead to which type of cellular death?
What specific reaction in metabolism requires Vitamin B12?
What specific reaction in metabolism requires Vitamin B12?
Which mechanism is used by 5-fluorouracil to hinder cellular processes?
Which mechanism is used by 5-fluorouracil to hinder cellular processes?
How does trimethoprim selectively inhibit bacteria?
How does trimethoprim selectively inhibit bacteria?
What is the role of NADPH in the folate metabolism process?
What is the role of NADPH in the folate metabolism process?
What is the significance of reducing FH4 availability in chemotherapy?
What is the significance of reducing FH4 availability in chemotherapy?
Which vitamin deficiency can lead to hyperhomocysteinemia?
Which vitamin deficiency can lead to hyperhomocysteinemia?
What is a consequence of hyperhomocysteinemia on cardiovascular health?
What is a consequence of hyperhomocysteinemia on cardiovascular health?
Which enzyme deficiency is NOT associated with hyperhomocysteinemia?
Which enzyme deficiency is NOT associated with hyperhomocysteinemia?
What is a major dietary source of Vitamin B12?
What is a major dietary source of Vitamin B12?
Which of the following symptoms is NOT directly associated with Vitamin B12 deficiency?
Which of the following symptoms is NOT directly associated with Vitamin B12 deficiency?
What role does intrinsic factor play in Vitamin B12 absorption?
What role does intrinsic factor play in Vitamin B12 absorption?
What is the average daily intake of Vitamin B12 in micrograms?
What is the average daily intake of Vitamin B12 in micrograms?
What is NOT a symptom of pernicious anemia due to B12 deficiency?
What is NOT a symptom of pernicious anemia due to B12 deficiency?
Which of the following conditions is most directly caused by Vitamin B12 deficiency?
Which of the following conditions is most directly caused by Vitamin B12 deficiency?
What role does the intrinsic factor play in the absorption of Vitamin B12?
What role does the intrinsic factor play in the absorption of Vitamin B12?
What is the major implication of mild hyperhomocysteinemia?
What is the major implication of mild hyperhomocysteinemia?
Which of the following symptoms is a common neurological dysfunction associated with Vitamin B12 deficiency?
Which of the following symptoms is a common neurological dysfunction associated with Vitamin B12 deficiency?
What is the estimated average daily intake of Vitamin B12 required for adults?
What is the estimated average daily intake of Vitamin B12 required for adults?
What is a primary function of S-adenosylmethionine (SAM) in human metabolism?
What is a primary function of S-adenosylmethionine (SAM) in human metabolism?
Which form of tetrahydrofolate (FH4) is specifically required for both purine synthesis and DNA synthesis?
Which form of tetrahydrofolate (FH4) is specifically required for both purine synthesis and DNA synthesis?
What role does vitamin B12 play in the metabolism of homocysteine?
What role does vitamin B12 play in the metabolism of homocysteine?
Which coenzyme is primarily involved in the transfer of carbon dioxide (CO2) in metabolic reactions?
Which coenzyme is primarily involved in the transfer of carbon dioxide (CO2) in metabolic reactions?
What is the biochemical basis for using methotrexate in cancer treatment?
What is the biochemical basis for using methotrexate in cancer treatment?
Which of the following is NOT a function of tetrahydrofolate (FH4)?
Which of the following is NOT a function of tetrahydrofolate (FH4)?
What important dietary source is often required for adequate vitamin B12 absorption?
What important dietary source is often required for adequate vitamin B12 absorption?
Which of the following conditions is primarily associated with deficiencies in both vitamin B12 and folate?
Which of the following conditions is primarily associated with deficiencies in both vitamin B12 and folate?
Which one-carbon unit is specifically utilized in the conversion of dUMP to dTMP?
Which one-carbon unit is specifically utilized in the conversion of dUMP to dTMP?
What is the primary mechanism by which folate deficiency leads to megaloblastic anemia?
What is the primary mechanism by which folate deficiency leads to megaloblastic anemia?
Which of the following is NOT a source of one-carbon groups transferred to FH4?
Which of the following is NOT a source of one-carbon groups transferred to FH4?
What type of anemia is associated with impaired cell division due to folate deficiency?
What type of anemia is associated with impaired cell division due to folate deficiency?
Which biosynthetic function is HB4 particularly important for?
Which biosynthetic function is HB4 particularly important for?
Which cell types are particularly affected by one-carbon metabolism disruptions due to folate deficiency?
Which cell types are particularly affected by one-carbon metabolism disruptions due to folate deficiency?
From which group does Vitamin B12 obtain a methyl group in one-carbon metabolism?
From which group does Vitamin B12 obtain a methyl group in one-carbon metabolism?
What happens to red blood cells as a result of folate deficiency?
What happens to red blood cells as a result of folate deficiency?
Which enzyme is directly involved in the synthesis of thymidine from dUMP using FH4?
Which enzyme is directly involved in the synthesis of thymidine from dUMP using FH4?
What clinical condition results from the release of large reticulocytes into circulation due to folate deficiency?
What clinical condition results from the release of large reticulocytes into circulation due to folate deficiency?
Which vitamin is essential for the transfer of a methyl group from FH4-CH3 to homocysteine?
Which vitamin is essential for the transfer of a methyl group from FH4-CH3 to homocysteine?
What condition might result from a deficiency in Vitamin B12 or methionine synthase?
What condition might result from a deficiency in Vitamin B12 or methionine synthase?
What is the primary action of methotrexate in relation to folate metabolism?
What is the primary action of methotrexate in relation to folate metabolism?
Which of the following statements about S-adenosylmethionine (SAM) is true?
Which of the following statements about S-adenosylmethionine (SAM) is true?
Which of the following drugs specifically inhibits bacterial dihydrofolate reductase?
Which of the following drugs specifically inhibits bacterial dihydrofolate reductase?
What term describes the situation where functional folate is locked in the FH4-CH3 form due to B12 deficiency?
What term describes the situation where functional folate is locked in the FH4-CH3 form due to B12 deficiency?
What is the mechanism by which 5-Fluorouracil induces cell death?
What is the mechanism by which 5-Fluorouracil induces cell death?
What are the potential health effects of functional folate deficiency due to Vitamin B12 deficiency?
What are the potential health effects of functional folate deficiency due to Vitamin B12 deficiency?
Which compound is directly formed from the rearrangement involving Vitamin B12?
Which compound is directly formed from the rearrangement involving Vitamin B12?
Which of the following reactions does NOT require methyl donations from SAM?
Which of the following reactions does NOT require methyl donations from SAM?
Hyperhomocysteinemia can arise from which of the following factors?
Hyperhomocysteinemia can arise from which of the following factors?
The term 'thymineless death' specifically refers to a consequence of the inhibition of which enzyme?
The term 'thymineless death' specifically refers to a consequence of the inhibition of which enzyme?
Sulfonamides inhibit bacterial growth by targeting which specific metabolic step?
Sulfonamides inhibit bacterial growth by targeting which specific metabolic step?
Which of the following is NOT a consequence of DNA synthesis deficiency associated with functional folate deficiency?
Which of the following is NOT a consequence of DNA synthesis deficiency associated with functional folate deficiency?
Both methotrexate and 5-Fluorouracil are effective in cancer treatment because they reduce the availability of which compound?
Both methotrexate and 5-Fluorouracil are effective in cancer treatment because they reduce the availability of which compound?
What can result from the trapping of folate as FH4-CH3?
What can result from the trapping of folate as FH4-CH3?
Which reaction is most directly impacted by a deficiency in methionine synthase?
Which reaction is most directly impacted by a deficiency in methionine synthase?
In terms of their action mechanism, how do methotrexate and trimethoprim differ?
In terms of their action mechanism, how do methotrexate and trimethoprim differ?
What role does NADPH play in folate metabolism?
What role does NADPH play in folate metabolism?
Methotrexate and 5-Fluorouracil are both used in chemotherapy primarily due to their effects on which biological process?
Methotrexate and 5-Fluorouracil are both used in chemotherapy primarily due to their effects on which biological process?
Flashcards
Tetrahydrofolate (FH4)
Tetrahydrofolate (FH4)
A key coenzyme in one-carbon metabolism involved in transferring activated one-carbon groups.
Tetrahydrofolate (FH4)
Tetrahydrofolate (FH4)
The active form of folate, essential for DNA synthesis, amino acid metabolism, and red blood cell production.
Dihydrofolate Reductase (DHFR)
Dihydrofolate Reductase (DHFR)
An enzyme that converts dihydrofolate (FH2) to tetrahydrofolate (FH4), the active form of folate, using NADPH as a reducing agent.
One-Carbon Metabolism
One-Carbon Metabolism
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Thymine Synthesis
Thymine Synthesis
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Purine Synthesis
Purine Synthesis
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Vitamin B12
Vitamin B12
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S-adenosylmethionine (SAM)
S-adenosylmethionine (SAM)
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What is tetrahydrofolic acid (FH4)?
What is tetrahydrofolic acid (FH4)?
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What is the role of FH4 in purine synthesis?
What is the role of FH4 in purine synthesis?
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How does FH4 contribute to DNA synthesis?
How does FH4 contribute to DNA synthesis?
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What happens when there is a deficiency of FH4?
What happens when there is a deficiency of FH4?
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Why is folate important for health?
Why is folate important for health?
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Methotrexate
Methotrexate
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Trimethoprim
Trimethoprim
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Sulfonamides
Sulfonamides
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5-Fluorouracil
5-Fluorouracil
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Thymineless Death
Thymineless Death
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Vitamin B12 (Cobalamin)
Vitamin B12 (Cobalamin)
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Methylmalonyl-CoA Mutase
Methylmalonyl-CoA Mutase
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Homocysteine Remethylation
Homocysteine Remethylation
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Hyperhomocysteinemia
Hyperhomocysteinemia
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Methionine Synthase
Methionine Synthase
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Methylene FH4 reductase (MTHFR)
Methylene FH4 reductase (MTHFR)
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Cystathionine synthase
Cystathionine synthase
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Pernicious Anemia
Pernicious Anemia
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Vitamin B12 deficiency
Vitamin B12 deficiency
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Intrinsic factor
Intrinsic factor
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Transcobalamin II
Transcobalamin II
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Folate-trap hypothesis
Folate-trap hypothesis
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Functional folate deficiency
Functional folate deficiency
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Methylenetetrahydrofolate reductase (MTHFR)
Methylenetetrahydrofolate reductase (MTHFR)
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Folate Trap
Folate Trap
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What is FH4's role in purine synthesis?
What is FH4's role in purine synthesis?
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What happens with FH4 deficiency?
What happens with FH4 deficiency?
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How is dTMP synthesized?
How is dTMP synthesized?
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What is the function of formyl-FH4?
What is the function of formyl-FH4?
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What is the role of THF in purine and thymidine synthesis?
What is the role of THF in purine and thymidine synthesis?
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What is the one-carbon pool?
What is the one-carbon pool?
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How does vitamin B12 use FH4?
How does vitamin B12 use FH4?
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What are the consequences of folate deficiency?
What are the consequences of folate deficiency?
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What is methotrexate and what does it do?
What is methotrexate and what does it do?
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How do trimethoprim and sulfonamides target bacterial growth?
How do trimethoprim and sulfonamides target bacterial growth?
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Why are drugs that target folate metabolism effective in cancer treatment?
Why are drugs that target folate metabolism effective in cancer treatment?
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How does 5-Fluorouracil inhibit DNA synthesis?
How does 5-Fluorouracil inhibit DNA synthesis?
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What are the two key metabolic reactions that vitamin B12 is involved in?
What are the two key metabolic reactions that vitamin B12 is involved in?
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How is vitamin B12 involved in the conversion of L-methylmalonyl-CoA to succinyl CoA?
How is vitamin B12 involved in the conversion of L-methylmalonyl-CoA to succinyl CoA?
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How is vitamin B12 involved in the conversion of homocysteine to methionine?
How is vitamin B12 involved in the conversion of homocysteine to methionine?
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What are the consequences of vitamin B12 deficiency?
What are the consequences of vitamin B12 deficiency?
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What is the folate-trap hypothesis?
What is the folate-trap hypothesis?
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What is a functional folate deficiency?
What is a functional folate deficiency?
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What is the role of vitamin B12 in methionine synthesis?
What is the role of vitamin B12 in methionine synthesis?
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What is S-adenosylmethionine (SAM) and its role?
What is S-adenosylmethionine (SAM) and its role?
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What is the role of methylenetetrahydrofolate reductase (MTHFR)?
What is the role of methylenetetrahydrofolate reductase (MTHFR)?
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What is hyperhomocysteinemia?
What is hyperhomocysteinemia?
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What happens in methionine synthase deficiency?
What happens in methionine synthase deficiency?
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What are the neurological consequences of B12 deficiency?
What are the neurological consequences of B12 deficiency?
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How does vitamin B12 contribute to the folate cycle?
How does vitamin B12 contribute to the folate cycle?
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What are the multiple roles of SAM in metabolism?
What are the multiple roles of SAM in metabolism?
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Study Notes
Vitamins in One Carbon Metabolism
- Vitamins involved in one-carbon metabolism include tetrahydrofolate (FH4), vitamin B12, and S-adenosylmethionine (SAM).
- These vitamins play critical roles in various reactions, including DNA synthesis, one-carbon transfer reactions, and the synthesis of other molecules/hormones.
- Methotrexate and 5-fluorouracil are used in chemotherapy to disrupt the folate cycle.
- Vitamin B12 is involved in two enzymatic reactions: methylmalonyl-CoA mutase and methionine synthase.
Learning Objectives
- Understand the functions of one-carbon metabolism (FH4, B12, and SAM).
- Evaluate the biochemical basis of using methotrexate and 5-fluorouracil in chemotherapy.
- Explain the role of formyl-FH4 and methylene-FH4 in DNA synthesis, megaloblastic anemia, and neural tube defects.
- Describe the process of vitamin B12 absorption, including the role of intrinsic factor and R-binders.
- Detail the function of B12 in SAM synthesis and folate regeneration, including the transfer of methyl groups from FH4 to homocysteine to form methionine.
- Explain the pathophysiology of B12 and folate deficiencies.
- Detail the functions of the one-carbon components carried by FH4 for various metabolic processes.
Functions of One-Carbon Metabolism
- One-carbon metabolism involves the transfer of activated one-carbon units from a donor to an acceptor molecule.
- Tetrahydrofolate (FH4) is a crucial carrier for one-carbon units (methyl, methylene, formyl).
- Vitamin B12 is a coenzyme for converting methyl-FH4 to methionine, which is essential for SAM synthesis.
- SAM is the main donor of methyl groups in many metabolic processes.
- The process allows for transfer of carbon groups for different types of biological molecules.
Folate
- Folate consists of three components: pteridine ring, para-aminobenzoic acid (PABA), and glutamate.
- The active form of folate is tetrahydrofolate (FH4).
- FH4 carries one-carbon units (methyl, methylene, formyl) required for various biosynthetic reactions.
- Dihydrofolate reductase (DHFR) converts folate to FH2 and then FH4, requiring NADPH.
Importance of FH4 in Biosynthetic Reactions
- FH4-related one-carbon units participate in DNA synthesis, purine synthesis, and thymidine synthesis.
- Vitamin B12 obtains a methyl group from 5-methyl-FH4.
Synthesis of Purines and Thymidine
- The synthesis of all purines and thymidine requires THF as a one-carbon donor.
Deficiency of Folate
- Folate deficiency leads to megaloblastic anemia due to impaired DNA synthesis.
- Symptoms include decreased red blood cell number, macrocytic, normochromic red blood cells (megaloblasts), and impaired cell division.
- Inadequate folate during pregnancy increases the risk of neural tube defects (like spina bifida).
Folate Metabolism and Chemotherapy
- Folate analogs (like methotrexate) inhibit DHFR, disrupting the folate cycle.
- 5-fluorouracil is an analog; it competitively inhibits thymidylate synthase.
- Both drugs cause "thymineless death."
Vitamin B12
- B12 (cobalamin) acts as a coenzyme for two reactions:
- methylmalonyl-CoA mutase (methylmalonyl-CoA → succinyl CoA).
- homocysteine methyltransferase (homocysteine → methionine).
Functions of Vitamin B12
- Rearrangement of L-methylmalonyl-CoA to succinyl CoA
- Transfer of methyl groups from FH4-CH3 to homocysteine to form methionine
- B12 is needed for SAM synthesis and FH4 regeneration, involving specific enzymes.
Deficiency of B12
- Dietary deficiency or lack of intrinsic factor can lead to pernicious anemia, neurological issues (like demyelination), and hyperhomocysteinemia.
- Deficiency of B12 interferes with folate function, causing a "folate-trap" by preventing the regeneration of one-carbon groups carried by FH4.
Sources of Vitamin B12
- Meat, fish, eggs, and milk are major dietary sources.
- Average daily intake is 5-30 µg, with 1-5 µg absorbed.
- RDA is 2.4 µg/day.
- Deficiency usually takes years to develop on a diet lacking this vitamin.
Vitamin B12 Absorption
- B12 binds R-binders (secreted by salivary glands and stomach).
- In the small intestine, R-binders are digested.
- B12 binds to intrinsic factor (secreted by gastric mucosa).
- The intrinsic factor-B12 complex binds to receptors in the ileum and is internalized.
- Transcobalamin II delivers B12 to tissues.
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Description
Test your knowledge on folate metabolism, its one-carbon units, and the implications of deficiency in rapidly dividing cells. This quiz explores key reactions and consequences associated with folate. Assess your understanding of how folate interacts with cellular processes and its role in purine and thymidine synthesis.
