One Carbon Unit Metabolism Quiz

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.

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.