Podcast
Questions and Answers
Which of the following clinical manifestations is NOT associated with folate deficiency?
Which of the following clinical manifestations is NOT associated with folate deficiency?
What is the primary role of tetrahydrofolate (THF) in folate metabolism?
What is the primary role of tetrahydrofolate (THF) in folate metabolism?
How does methotrexate, as a folate antagonist, primarily exert its effects?
How does methotrexate, as a folate antagonist, primarily exert its effects?
Which of the following conditions is primarily associated with inadequate folate intake during pregnancy?
Which of the following conditions is primarily associated with inadequate folate intake during pregnancy?
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Which carrier is responsible for the transfer of a methyl group in one-carbon metabolism?
Which carrier is responsible for the transfer of a methyl group in one-carbon metabolism?
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What is the primary carbon source of one-carbon groups in humans?
What is the primary carbon source of one-carbon groups in humans?
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Which product is synthesized from homocysteine using CH3-THF?
Which product is synthesized from homocysteine using CH3-THF?
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Which enzyme facilitates the production of N5,N10-methylene-FH4 from serine?
Which enzyme facilitates the production of N5,N10-methylene-FH4 from serine?
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Which of the following reactions involves the transfer of one-carbon units in the synthesis of purine nucleotides?
Which of the following reactions involves the transfer of one-carbon units in the synthesis of purine nucleotides?
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Which amino acid leads to the production of formyl THF as a result of its metabolism?
Which amino acid leads to the production of formyl THF as a result of its metabolism?
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Study Notes
One Carbon Unit Metabolism
- Covered by Dr. Walaa Ibrahim & Dr. Reem Sallam
- Medical Biochemistry & Molecular Biology
Intended Learning Outcomes
- Identify forms of one-carbon units
- Identify carriers of one-carbon units
- Describe sources and fate of each unit
- Explain biomedical importance of Folic Acid analogues
- Enumerate clinical manifestations of folate deficiency
Overview
- Some synthetic pathways need single carbon groups
- These single carbon groups are transferred from carrier compounds like THF and SAM to specific structures being synthesized
- The one carbon pool refers to single carbon units attached to these carriers
Types of One Carbon Units
- Methyl group (-CH3)
- Methylene group (-CH2-)
- Methenyl group (-CH=)
- Formyl group (-CH=O)
- Formimino group (-CH=NH)
- CO2 group
Carriers of One-Carbon Units
- 1-Biotin carries CO2
- Tetrahydrofolate (THF) carries -CH3, CH2, CH=, CHO, CHN
- S-adenosyl methionine carries CH3
1-Biotin
- Carries CO2
- Involved in carboxylation reactions, but not part of the one-carbon pool
2-Tetrahydrofolate (THF)
- The biologically active form of folic acid
- Produced by two-step reduction of folate by dihydrofolate reductase (DHFR)
- DHFR is an enzyme dependent on NADPH
- Folic acid reduced to dihydrofolate then to tetrahydrofolate
Key Feature of THF
- Carries various one-carbon groups
- One-carbon groups attach to N5 or N10, or bridge between N5 and N10
- The collection of one-carbon groups attached to THF is the one-carbon pool
Oxidation States of One-Carbon Pool
- Most reduced: Methyl (-CH3)
- Intermediate: Methylene (-CH2-)
- Most oxidized: Formyl (-CHO), Formimino (-CH=NH), Methenyl (-CH=)
Sources of One-Carbon Units
- Glycine: a-carbon
- Serine: β-carbon (major source)
- Tryptophan: forms formyl kynurenine which produces formyl THF
- Histidine: forms formimino glutamate which produces formimino THF
Example: Serine Hydroxymethyl Transferase
- Serine is a major carbon source for one-carbon units
- This reaction is catalyzed by serine hydroxymethyl transferase
- PLP is a coenzyme for this reaction
- Produces glycine and N5,N10-methylene-FH4
Fates of One-Carbon Units
- Synthesis of serine from glycine
- Synthesis of methionine from homocysteine using CH3-THF
- Synthesis of purine nucleotides using formyl THF
- Synthesis of dTMP from dUMP using methylene group (-CH2)
Synthesis of Methionine from Homocysteine
- Methyl-THF is used in this process
- This process involves SAM (S-adenosyl methionine) and SAH
Synthesis of Purine Nucleotides
- Formyl THF is the source of carbon 2 and 8
- This is important for DNA synthesis (especially in rapidly dividing cells)
Synthesis of dTMP from dUMP
- The source of carbon is N5,N10-methylene-THF
- Two hydrogen atoms from THF are used in the reaction
- Dihydrofolate (DHF) is produced then reduced by dihydrofolate reductase (DHFR) to regenerate THF
Tetrahydrofolate (THF) Requirements
- THF needed for dTMP and purine base synthesis for DNA replication
- THF needed for cell division
- Deficiency or blockage in THF synthesis leads to decreased rate of cell division and growth
Folic Acid Analogues (e.g., Methotrexate)
- Methotrexate is an inhibitor of human dihydrofolate reductase (DHFR), preventing folate activation to THF
- A potent anti-cancer drug
Clinical Manifestations of Folate Deficiency
- Megaloblastic anemia (macrocytic, hyperchromic)
- Glossitis and gastrointestinal disturbances
- Neural tube defects (NTDs) occur in first week's pregnancy
Practice Questions and Answers (Some)
-
Practice Question 1: What is the source of carbon 2 and 8 in purine nucleotides?
- Answer: Formyl group carried by tetrahydrofolate (THF)
-
Practice Question 2: Mechanism of action of methotrexate?
- Answer: Inhibits dihydrofolate reductase (DHFR) enzyme
-
Practice Question 3: Which one-carbon unit is often carried in neural tube defects?
- Answer: Methyl, methylene, methenyl, Formyl, formimino.
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Description
Test your knowledge on the metabolism of one-carbon units, including their carriers and biomedical importance. This quiz covers the various types of one-carbon units, their sources and fates, as well as the implications of folate deficiency. Ideal for students in Medical Biochemistry and Molecular Biology.
