Essential Vitamins in Metabolism: Impacts on Fatty Acid, Triglyceride, and Nucleotide Pathways

Table 1: Fatty Acid and Triglyceride Metabolism

Vitamin Impaired Reaction Enzyme Affected Consequence
Riboflavin (B2) β-oxidation of fatty acids Acyl-CoA dehydrogenase Reduced ATP production from fats
Niacin (B3) β-oxidation of fatty acids Hydroxyacyl-CoA dehydrogenase Energy generation from fats reduced
Triglyceride synthesis Glycerol-3-phosphate dehydrogenase Impaired triglyceride formation
Biotin Fatty acid synthesis Acetyl-CoA carboxylase Disrupted synthesis of fatty acids
Odd-chain fatty acid metabolism Propionyl-CoA carboxylase Accumulation of toxic intermediates
Vitamin B12 Odd-chain fatty acid metabolism Methylmalonyl-CoA mutase Impaired odd-chain fatty acid breakdown
Vitamin B6 (PLP) Essential fatty acid metabolism Δ6-Desaturase Reduced production of essential fatty acids

Key Reactions Explained:

  1. β-Oxidation (Riboflavin, Niacin):
    • Acyl-CoA dehydrogenase: FAD-dependent step in β-oxidation of fatty acids.
    • Hydroxyacyl-CoA dehydrogenase: NAD-dependent step in the oxidation of fatty acids.
  2. Fatty Acid Synthesis (Biotin):
    • Acetyl-CoA carboxylase: Initiates fatty acid synthesis by forming malonyl-CoA
  3. Triglyceride Synthesis (Niacin):
    • Glycerol-3-phosphate dehydrogenase: Converts DHAP to glycerol-3-phosphate for triglyceride assembly.
  4. Odd-Chain Fatty Acid Metabolism (Biotin, Vitamin B12):
    • Biotin-dependent Propionyl-CoA carboxylase produces methylmalonyl-CoA.
    • Vitamin B12-dependent methylmalonyl-CoA mutase converts methylmalonyl-CoA to succinyl-CoA for TCA cycle entry.

Table 2: Vitamin Deficiencies and Impairments in Nucleotide Metabolism

Vitamin Impaired Reaction Enzyme Affected Consequence
Folate (B9) Synthesis of thymidylate (dTMP) from dUMP Thymidylate synthase (via 5,10-Methylene-THF) Impaired DNA synthesis, megaloblastic anemia
Purine synthesis Formyltransferases Reduced nucleotide production
Vitamin B12 Conversion of homocysteine to methionine Methionine synthase Disrupted folate recycling, impaired DNA synthesis
Riboflavin (B2) Regeneration of thioredoxin for ribonucleotide reduction Thioredoxin reductase (FAD-dependent) Indirectly impaired DNA replication and repair due to lack of deoxyribonucleotide production
Thiamine (B1) Pentose phosphate pathway for ribose-5-phosphate synthesis Transketolase Reduced availability of ribose for nucleotide synthesis
Pyridoxine (B6) Synthesis of purines from glycine and formate Enzymes involved in one-carbon metabolism Disrupted purine synthesis

Key Reactions Explained:

  1. Folate (B9):
    • Thymidylate synthesis: Converts dUMP to dTMP for DNA synthesis.
    • Purine synthesis: Provides carbon units required for nucleotide bases (adenine, guanine).
  2. Vitamin B12:
    • Supports folate recycling, essential for one-carbon transfers in nucleotide biosynthesis.
  3. Riboflavin (B2):
    • Required for ribonucleotide reductase activity, converting ribonucleotides to deoxyribonucleotides.
  4. Thiamine (B1):
    • Participates in the pentose phosphate pathway to generate ribose-5-phosphate, a precursor for nucleotide synthesis.
  5. Vitamin B6:
    • Facilitates reactions in amino acid and one-carbon metabolism critical for purine ring assembly.
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