L7 Vitamins in One Carbon Metabolism
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Questions and Answers

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?

  • 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?

  • 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?

    <p>Formyl-FH4</p> Signup and view all the answers

    Which of the following represents a direct effect of folate deficiency?

    <p>Impaired cell division</p> Signup and view all the answers

    What role does Tetrahydrofolate (FH4) play in DNA synthesis?

    <p>It accepts one-carbon groups during thymine synthesis.</p> Signup and view all the answers

    Which statement accurately describes the function of Vitamin B12 in one-carbon metabolism?

    <p>It acts as a coenzyme transferring a methyl group to homocysteine.</p> Signup and view all the answers

    What is the significance of formyl-FH4 in human metabolism?

    <p>It is required for the synthesis of purines.</p> Signup and view all the answers

    What is a primary consequence of Vitamin B12 deficiency?

    <p>Megaloblastic anemia.</p> Signup and view all the answers

    How does methotrexate influence one-carbon metabolism?

    <p>It inhibits dihydrofolate reductase.</p> Signup and view all the answers

    What is the primary role of S-adenosylmethionine (SAM) in metabolism?

    <p>To donate methyl groups for various biochemical reactions.</p> Signup and view all the answers

    What enzyme converts folate to its active form Tetrahydrofolate (FH4)?

    <p>Dihydrofolate reductase.</p> Signup and view all the answers

    Which aspect of folate metabolism is crucial for preventing neural tube defects?

    <p>Importance of formyl-FH4 in DNA synthesis.</p> Signup and view all the answers

    What is the role of vitamin B12 in the conversion of homocysteine to methionine?

    <p>It donates a methyl group.</p> Signup and view all the answers

    What happens to folate if CH3 cannot be removed from FH4-CH3?

    <p>It accumulates and leads to a functional folate deficiency.</p> Signup and view all the answers

    Which process is directly associated with S-adenosylmethionine (SAM)?

    <p>Methyl donation for various biochemical reactions.</p> Signup and view all the answers

    What is the consequence of B12 deficiency on folate metabolism?

    <p>Results in a folate-trap phenomenon.</p> Signup and view all the answers

    What are the health effects associated with functional folate deficiency due to B12 deficiency?

    <p>Hyperhomocysteinemia.</p> Signup and view all the answers

    The methyl-trap hypothesis indicates that what occurs in the absence of adequate B12?

    <p>Functional folate is depleted and trapped.</p> Signup and view all the answers

    Which molecule donates methyl groups in most reactions requiring one-carbon units?

    <p>SAM.</p> Signup and view all the answers

    What could contribute to hyperhomocysteinemia?

    <p>Nutritional deficiencies and genetic factors.</p> Signup and view all the answers

    What is the primary target of the folate analog methotrexate?

    <p>Inhibits human dihydrofolate reductase</p> Signup and view all the answers

    Which drug inhibits bacterial growth by affecting folate metabolism?

    <p>Sulfonamides</p> Signup and view all the answers

    Both methotrexate and 5-fluorouracil lead to which type of cellular death?

    <p>Thymineless death</p> Signup and view all the answers

    What specific reaction in metabolism requires Vitamin B12?

    <p>Rearrangement of L-methylmalonyl-CoA to succinyl CoA</p> Signup and view all the answers

    Which mechanism is used by 5-fluorouracil to hinder cellular processes?

    <p>Inhibition of thymidylate synthase</p> Signup and view all the answers

    How does trimethoprim selectively inhibit bacteria?

    <p>It inhibits bacterial dihydrofolate reductase</p> Signup and view all the answers

    What is the role of NADPH in the folate metabolism process?

    <p>It serves as an electron carrier</p> Signup and view all the answers

    What is the significance of reducing FH4 availability in chemotherapy?

    <p>It limits the pool of active folate needed for DNA and RNA synthesis</p> Signup and view all the answers

    Which vitamin deficiency can lead to hyperhomocysteinemia?

    <p>Vitamin B12</p> Signup and view all the answers

    What is a consequence of hyperhomocysteinemia on cardiovascular health?

    <p>Increased risk of adverse cardiovascular events</p> Signup and view all the answers

    Which enzyme deficiency is NOT associated with hyperhomocysteinemia?

    <p>Amino acid decarboxylase</p> Signup and view all the answers

    What is a major dietary source of Vitamin B12?

    <p>Dairy products</p> Signup and view all the answers

    Which of the following symptoms is NOT directly associated with Vitamin B12 deficiency?

    <p>Severe muscle weakness</p> Signup and view all the answers

    What role does intrinsic factor play in Vitamin B12 absorption?

    <p>It is essential for B12 binding in the intestine</p> Signup and view all the answers

    What is the average daily intake of Vitamin B12 in micrograms?

    <p>5-30 μg</p> Signup and view all the answers

    What is NOT a symptom of pernicious anemia due to B12 deficiency?

    <p>Increased appetite</p> Signup and view all the answers

    Which of the following conditions is most directly caused by Vitamin B12 deficiency?

    <p>Megaloblastic anemia</p> Signup and view all the answers

    What role does the intrinsic factor play in the absorption of Vitamin B12?

    <p>It binds to B12 and facilitates its internalization in the ileum</p> Signup and view all the answers

    What is the major implication of mild hyperhomocysteinemia?

    <p>It confers an increased risk of cardiovascular events</p> Signup and view all the answers

    Which of the following symptoms is a common neurological dysfunction associated with Vitamin B12 deficiency?

    <p>Spastic gait disturbance</p> Signup and view all the answers

    What is the estimated average daily intake of Vitamin B12 required for adults?

    <p>5-30 μg</p> Signup and view all the answers

    What is a primary function of S-adenosylmethionine (SAM) in human metabolism?

    <p>Methylation of various biomolecules</p> Signup and view all the answers

    Which form of tetrahydrofolate (FH4) is specifically required for both purine synthesis and DNA synthesis?

    <p>Formyl-FH4</p> Signup and view all the answers

    What role does vitamin B12 play in the metabolism of homocysteine?

    <p>Transfers a methyl group to homocysteine to form methionine</p> Signup and view all the answers

    Which coenzyme is primarily involved in the transfer of carbon dioxide (CO2) in metabolic reactions?

    <p>Biotin</p> Signup and view all the answers

    What is the biochemical basis for using methotrexate in cancer treatment?

    <p>Inhibits dihydrofolate reductase, thus decreasing FH4 availability</p> Signup and view all the answers

    Which of the following is NOT a function of tetrahydrofolate (FH4)?

    <p>Regeneration of dihydrofolate reductase (DHFR)</p> Signup and view all the answers

    What important dietary source is often required for adequate vitamin B12 absorption?

    <p>Animal-based foods</p> Signup and view all the answers

    Which of the following conditions is primarily associated with deficiencies in both vitamin B12 and folate?

    <p>Megaloblastic anemia</p> Signup and view all the answers

    Which one-carbon unit is specifically utilized in the conversion of dUMP to dTMP?

    <p>Methylene (CH2)</p> Signup and view all the answers

    What is the primary mechanism by which folate deficiency leads to megaloblastic anemia?

    <p>Reduced synthesis of red blood cells from stem cells</p> Signup and view all the answers

    Which of the following is NOT a source of one-carbon groups transferred to FH4?

    <p>Acetyl-CoA</p> Signup and view all the answers

    What type of anemia is associated with impaired cell division due to folate deficiency?

    <p>Megaloblastic anemia</p> Signup and view all the answers

    Which biosynthetic function is HB4 particularly important for?

    <p>Synthesis of purine rings</p> Signup and view all the answers

    Which cell types are particularly affected by one-carbon metabolism disruptions due to folate deficiency?

    <p>Stem cells and immune system cells</p> Signup and view all the answers

    From which group does Vitamin B12 obtain a methyl group in one-carbon metabolism?

    <p>5-methyl-FH4</p> Signup and view all the answers

    What happens to red blood cells as a result of folate deficiency?

    <p>They decrease in number leading to anemia.</p> Signup and view all the answers

    Which enzyme is directly involved in the synthesis of thymidine from dUMP using FH4?

    <p>Thymidylate synthase</p> Signup and view all the answers

    What clinical condition results from the release of large reticulocytes into circulation due to folate deficiency?

    <p>Megaloblastic anemia</p> Signup and view all the answers

    Which vitamin is essential for the transfer of a methyl group from FH4-CH3 to homocysteine?

    <p>Vitamin B12</p> Signup and view all the answers

    What condition might result from a deficiency in Vitamin B12 or methionine synthase?

    <p>Accumulation of FH4-CH3</p> Signup and view all the answers

    What is the primary action of methotrexate in relation to folate metabolism?

    <p>Reduces the availability of active folate</p> Signup and view all the answers

    Which of the following statements about S-adenosylmethionine (SAM) is true?

    <p>SAM is involved in activating and inactivating various compounds.</p> Signup and view all the answers

    Which of the following drugs specifically inhibits bacterial dihydrofolate reductase?

    <p>Trimethoprim</p> Signup and view all the answers

    What term describes the situation where functional folate is locked in the FH4-CH3 form due to B12 deficiency?

    <p>Methyl-trap hypothesis</p> Signup and view all the answers

    What is the mechanism by which 5-Fluorouracil induces cell death?

    <p>Inhibition of thymidylate synthase</p> Signup and view all the answers

    What are the potential health effects of functional folate deficiency due to Vitamin B12 deficiency?

    <p>Fatigue and shortness of breath</p> Signup and view all the answers

    Which compound is directly formed from the rearrangement involving Vitamin B12?

    <p>Succinyl CoA</p> Signup and view all the answers

    Which of the following reactions does NOT require methyl donations from SAM?

    <p>Conversion of homocysteine to methionine</p> Signup and view all the answers

    Hyperhomocysteinemia can arise from which of the following factors?

    <p>Genetic predisposition</p> Signup and view all the answers

    The term 'thymineless death' specifically refers to a consequence of the inhibition of which enzyme?

    <p>Thymidylate synthase</p> Signup and view all the answers

    Sulfonamides inhibit bacterial growth by targeting which specific metabolic step?

    <p>Synthesis of pteroic acid</p> Signup and view all the answers

    Which of the following is NOT a consequence of DNA synthesis deficiency associated with functional folate deficiency?

    <p>Improved wound healing</p> Signup and view all the answers

    Both methotrexate and 5-Fluorouracil are effective in cancer treatment because they reduce the availability of which compound?

    <p>Folate</p> Signup and view all the answers

    What can result from the trapping of folate as FH4-CH3?

    <p>Functional folate deficiency</p> Signup and view all the answers

    Which reaction is most directly impacted by a deficiency in methionine synthase?

    <p>Transfer of a methyl group to homocysteine</p> Signup and view all the answers

    In terms of their action mechanism, how do methotrexate and trimethoprim differ?

    <p>Methotrexate inhibits human DHFR, while trimethoprim does not</p> Signup and view all the answers

    What role does NADPH play in folate metabolism?

    <p>It serves as a reducing agent in FH4 production</p> Signup and view all the answers

    Methotrexate and 5-Fluorouracil are both used in chemotherapy primarily due to their effects on which biological process?

    <p>Nucleic acid synthesis</p> Signup and view all the answers

    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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    L7 Vitamins in One Carbon Metabolism PDF

    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.

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