METABOLISM OF NUCLEOTIDES & ASSOCIATED DISEASES Flashcards
List the types of purine
- Adenine
- Guanine
List types of pyrimidine
- Uracil
- Thymine
- Cytosine
Explain the biochemical event that leads to production of uric acid
- The degradation of purine nucleotides occurs mainly in the liver.
- AMP is deaminated to produce IMP or also known as adenosine
- Adenosine is deaminated to inosine by adenosine deaminase (ADA).
- Inosine is then catalysed by the purine nucleoside phosphorylase (PNP) to convert to hypoxanthine.
- While, GMP is converted guanosine with the help from nucleotides
- Guanosine is then catalysed by the purine nucleoside phosphorylase to form guanine.
- Guanine is converted to xanthine with the help from guanase.
- In fact, hypoxanthine also is converted to xanthine with the help from xanthine oxidase.
- The pathway for degradation for purine merge at this hypoxanthine and guanine steps.
- Xanthine is converted to uric acid with the help from the xanthine oxidase.
- The excessive amount of uric acid produced going to lead to gout.
Explain why gout is seen in individuals with a partial deficiency of HGPRT
- Gout is seen in individuals with a partial deficiency of HGPRT is called as primary gout.
- In primary gout, the amount of HGPRT is deficient.
- This causes the amount of phosphoribosyl phyryphosphate (PRPP) to be increased.
- The increased amount of PRPP causes the amidotransferase which is an allosteric enzyme to be stimulated.
- The stimulation of amidotransferase causes the synthesis of nucleotides to be increased.
- Hence, the amount of degradation of nucleotides also will increases.
- Other than that, in primary gout, it also will increase the amount hypoxanthine and guanine.
- As we know, hypoxantine and guanine will merge at this point to form xanthine
- The high amount of hypoxanthine and guanine causes the amount of xanthine to be increased as well.
- Hence, excess uric acid will form.
- This excess uric acid causes gout.
Briefly explain how allopurinol helps in treating gout,
- Allopurinol is an analog of hypoxanthine.
- It will compete with hypoxanthine to bind with xanthine oxidase.
- In other words, allopurinol is a competitive inhibitor.
- Allopurinol will block the action of xanthine oxidase in substrate competition to form xanthine.
- Hence, allopurinol will become alloxanthine or oxypurinol which tightly bound to the xanthine oxidase to prevent any catalytic activity.
- Due to this, the formation of uric acid will be decreases.
- Hence, gout can be treated.
State the types of gout.
- Primary gout
- Secondary gout
Briefly explain the secondary gout
- Secondary gout happened due to multi- source such as leukemia and polycythemia.
- It also can occur during an anti-cancer chemotherapy.
- In secondary gout, there is an absent of HGPRT and deficiency of Glu-6- phosphate.
- Absent of HGPRT will lead to Lesch- Nyhan syndrome
- While, deficiency of glu-6-phosphate lead to von gierke’s disease.
State 5 symptoms of Lesch- Nyhan syndrome
- Hyperuricemia
- Mental retardation
- Neurological abnormalities
- Agressive
- Spasticity
- Bite fingers and lips
- Self destructive behavior
Briefly explain the biochemical basis of orotic aciduria
- Orotic aciduria is caused by the defects of the protein chain with enzyme activity of the last two step in the synthesis of pyrimidine which is the UMP synthetase.
- Hence, pyrimidine cannot be produced
- Therefore, normal growth cannot occur.
- In fact, orotic aciduria can lead to anemia
- However, this disease can be treated with cytidine and uridine,
- This diseases can be inherited through autosomal recessive disorder.
Briefly explain the menifestation of megaloblastic anaemia.
- Megaloblastic anaemia is a condition in which the bone marrow produces unusually large, structurally abnormal, immature RBC (megaloblast)
- Megaloblastic anaemia is caused by UMP synthase deficiency leading to inability of RBC precursors to synthesise DNA and to divide.
- This lead to large, partially replicated cells being released into blood vessel to attempt to replenish the dead cell.
State 3 importance of nucleotides.
- Nucleotides plays a roles in various biochemical reactions such as precursors for the synthesis of DNA and RNA as well as the energy molecules like ATP and GTP.
- Adenine nucleotide is a component of coenzymes such as NAD+, NADP+, FAD, and CoA.
- Nucleotides as metabolic regulator (effectors) such as cAMP, AMP, IMP and GMP.
WHAT IS DENOVO BIOSYNTHESIS OF PURINE?
DENOVO BIOSYNTHESIS IS:
- FROM THE BUILDING BLOCKS (RIBOSE 5 PHOSPHATE)
- IT WILL USE A LOT OF ENERGY (6 ATP) WHICH IS USE AS GROUP TRANSFER INSTEAD OF COUPLING
- IT IS VERY ACTIVE IN THE LIVER EXCEPT IN ERYTHROCYTES, BRAIN AND PMN.
WHAT IS SALVAGE PATHWAY OF PURINE?
SALVAGE PATHWAY IS:
- OCCUR IN ALL CELLS ESP LYMPHOCYTES
- SALVAGE OF FREE NITROGENOUS BASES.
- HYPOXANTHINE, GUANINE, ADENINE
STATE 3 FACTORS THAT CAN INFLUENCE THE EXCRETION OF URIC ACID.
KETONE BODIES
LACTATE
ASPIRIN
