Nucleotide and Vitamin Metabolism

🧬 Nucleotide Metabolism & Vitaminology

Ultimate Master Guide for CSIR-NET | GATE | DBT-BET

1. Purine Biosynthesis

Purines (Adenine, Guanine) are synthesized primarily in the liver. Unlike pyrimidines, the purine ring is constructed atom-by-atom directly onto a pre-existing Ribose-5-Phosphate (PRPP) molecule.

• Key Intermediate: IMP (Inosine Monophosphate) is the first purine nucleotide formed, acting as a branch point to synthesize both AMP and GMP.
• Rate-Limiting Enzyme: PRPP Glutamyl Amidotransferase (Inhibited by end-products AMP, GMP, and IMP).
• Salvage Pathway: Brain and RBCs cannot synthesize purines de novo. They salvage free bases using the enzyme HGPRT. A severe deficiency in HGPRT leads to Lesch-Nyhan Syndrome (hyperuricemia and self-mutilation).

2. Purine Catabolism & Gout

Unlike carbohydrates and lipids, the purine ring cannot be cleaved and oxidized for energy in humans. It is converted into a highly insoluble waste product: Uric Acid.

AMP / GMP → Xanthine → Uric Acid → Excreted in Urine

• Key Enzyme: Xanthine Oxidase catalyzes the final conversion of Xanthine to Uric Acid.
• Gout (Hyperuricemia): Overproduction or under-excretion of uric acid leads to the crystallization of monosodium urate in joints (typically the big toe), causing severe inflammation.
• Treatment (Allopurinol): Allopurinol is a structural analog of Hypoxanthine. It acts as a suicide (mechanism-based) inhibitor of Xanthine Oxidase, stopping uric acid production.

3. Pyrimidine Biosynthesis

Contrary to purines, the pyrimidine ring (Cytosine, Thymine, Uracil) is completely assembled first, and then attached to a PRPP molecule.

• Atom Sources: The entire ring comes from just two molecules: Aspartate and Carbamoyl Phosphate (which provides Glutamine and CO₂).
• Rate-Limiting Enzyme: CPS-II (Carbamoyl Phosphate Synthetase II), located in the cytosol. (Note: CPS-I is in the mitochondria for the Urea Cycle).
• Orotic Aciduria: A genetic defect in UMP Synthase leads to the massive accumulation of Orotic Acid in urine and megaloblastic anemia.

4. Pyrimidine Catabolism

Unlike purines, the pyrimidine ring can be completely cleaved and degraded in humans.

The end products of pyrimidine catabolism are highly water-soluble molecules: β-alanine (from Cytosine/Uracil), β-aminoisobutyrate (from Thymine), NH₃, and CO₂. Because these are highly soluble, pyrimidine catabolism rarely causes any disease or crystallization issues.

5. Fat-Soluble Vitamins (A, D, E, K)

These vitamins require bile salts and dietary fat for absorption. They are stored in the liver and adipose tissue, meaning excessive intake can lead to Hypervitaminosis (Toxicity).

Vitamin A (Retinoids)

Function: Precursor for Rhodopsin (vision in low light); maintains epithelial tissues.

Deficiency: Night blindness, Xerophthalmia (dry eyes).

Vitamin D (Calciferol)

Function: Acts as a steroid hormone to absorb Calcium and Phosphate from the gut.

Deficiency: Rickets (children), Osteomalacia (adults).

Vitamin E (Tocopherol)

Function: Major lipid-soluble antioxidant. Protects cell membranes from lipid peroxidation.

Deficiency: Rare. Hemolytic anemia, neurological deficits.

Vitamin K (Phylloquinone)

Function: Coenzyme for γ-carboxylation of glutamic acid (essential for blood clotting factors II, VII, IX, X).

Deficiency: Severe bleeding, hemorrhage. (Targeted by Warfarin).

6. Water-Soluble Vitamins (B-Complex & C)

These are generally not stored in the body (excess is excreted in urine), meaning they must be supplied continuously in the diet. They primarily function as crucial coenzymes in energy metabolism.

Vitamin Name	Active Coenzyme Form	Biochemical Function	Deficiency Disease
B1 (Thiamine)	Thiamine Pyrophosphate (TPP)	Decarboxylation (PDH complex, α-KGDH)	Beriberi, Wernicke-Korsakoff
B2 (Riboflavin)	FAD, FMN	Redox reactions (Succinate DH)	Cheilosis, Glossitis
B3 (Niacin)	NAD⁺, NADP⁺	Redox reactions (Dehydrogenases)	Pellagra (3 D's: Dermatitis, Diarrhea, Dementia)
B5 (Pantothenic Acid)	Coenzyme A (CoA)	Acyl carrier (Acetyl-CoA formation)	Rare (Burning foot syndrome)
B6 (Pyridoxine)	Pyridoxal Phosphate (PLP)	Transamination (ALT, AST), Decarboxylation	Neuropathy, Sideroblastic anemia
B7 (Biotin)	Enzyme-bound Biotin	Carboxylation (Pyruvate carboxylase). Inhibited by Avidin in raw eggs.	Dermatitis, Alopecia
B9 (Folate)	Tetrahydrofolate (THF)	1-Carbon transfer (Purine/pyrimidine synthesis)	Megaloblastic anemia, Neural tube defects
B12 (Cobalamin)	Methylcobalamin	Odd-chain fatty acid breakdown. Requires Intrinsic Factor for absorption.	Pernicious anemia, Subacute combined degeneration

🍊 Vitamin C (Ascorbic Acid)

Humans lack the enzyme L-gulonolactone oxidase and cannot synthesize Vitamin C.

• Biochemical Function: Acts as an essential cofactor for Prolyl Hydroxylase and Lysyl Hydroxylase. These enzymes hydroxylate proline and lysine residues in procollagen, allowing the collagen triple-helix to cross-link and stabilize.
• Secondary Function: A potent water-soluble antioxidant. Keeps iron in the reduced (Fe²⁺) state, aiding iron absorption in the gut.
• Deficiency (Scurvy): Results in defective, weak collagen. Symptoms include swollen, bleeding gums, poor wound healing, and easy bruising.