Purines and pyrimidines are essential components of nucleotides which form DNA RNA ATP and other biomolecules necessary for life. Their metabolism involves a complex process of synthesis degradation and recycling ensuring a steady supply for cellular functions.
This topic explores the metabolism of purine and pyrimidine their biological importance and the disorders associated with their dysfunction.
What Are Purines and Pyrimidines?
Purines and pyrimidines are nitrogenous bases that serve as building blocks for nucleotides.
- Purines include adenine (A) and guanine (G) which are found in both DNA and RNA.
- Pyrimidines include cytosine (C) thymine (T) in DNA and uracil (U) in RNA.
Metabolism of Purines
1. Purine Biosynthesis
Purine synthesis occurs primarily in the liver through the de novo pathway and the salvage pathway.
De Novo Purine Synthesis
- Begins with ribose-5-phosphate derived from the pentose phosphate pathway.
- The key intermediate inosine monophosphate (IMP) is formed and converted into adenosine monophosphate (AMP) and guanosine monophosphate (GMP).
- The enzyme glutamine phosphoribosyl pyrophosphate amidotransferase (PRPP amidotransferase) regulates the pathway.
Salvage Pathway for Purines
- Recycles purines from degraded nucleotides.
- Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and adenine phosphoribosyltransferase (APRT) play key roles in reusing purine bases.
2. Purine Degradation
- Purines break down into uric acid which is excreted in urine.
- The enzyme xanthine oxidase converts hypoxanthine to xanthine and then to uric acid.
- Excess uric acid can lead to gout a painful inflammatory condition caused by uric acid crystal buildup.
Metabolism of Pyrimidines
1. Pyrimidine Biosynthesis
Unlike purines pyrimidines are synthesized before being attached to ribose-phosphate.
De Novo Pyrimidine Synthesis
- Begins with carbamoyl phosphate (from glutamine and bicarbonate).
- Forms the key intermediate orotate which combines with PRPP to form uridine monophosphate (UMP).
- UMP is then converted to cytidine monophosphate (CMP) and thymidine monophosphate (TMP).
- Carbamoyl phosphate synthetase II (CPS II) is a key regulatory enzyme.
2. Pyrimidine Degradation
- Pyrimidines break down into β-alanine and β-aminoisobutyrate which are water-soluble and excreted easily.
- Unlike purine metabolism pyrimidine degradation does not produce harmful uric acid.
Regulation of Nucleotide Metabolism
- Feedback inhibition prevents overproduction of purines and pyrimidines.
- PRPP concentration controls nucleotide synthesis rates.
- Enzymes like xanthine oxidase and CPS II regulate purine and pyrimidine pathways.
Disorders Related to Purine and Pyrimidine Metabolism
1. Gout
- Caused by excess uric acid from purine degradation.
- Leads to joint pain and inflammation due to uric acid crystal deposits.
- Managed with allopurinol which inhibits xanthine oxidase.
2. Lesch-Nyhan Syndrome
- A genetic disorder caused by HGPRT deficiency.
- Leads to excessive uric acid production neurological problems and self-mutilating behavior.
3. Orotic Aciduria
- A defect in UMP synthase leading to excess orotic acid excretion.
- Causes megaloblastic anemia and growth delays.
- Treated with uridine supplements.
4. Adenosine Deaminase Deficiency (ADA Deficiency)
- Affects purine metabolism leading to Severe Combined Immunodeficiency (SCID).
- Results in immune system failure.
- Treatment includes gene therapy or enzyme replacement therapy.
Purine and pyrimidine metabolism plays a vital role in DNA synthesis energy production and cellular function. Proper regulation ensures normal biological processes while metabolic disorders can lead to severe health issues. Understanding these pathways helps in diagnosing and treating metabolic disorders effectively.
