Exam 3 Biochem-Lecture 34

What are purines and pyrimidines?

 

Purines and pyrimidines, often called bases, are nitrogen-containing heterocyclic compounds.

Purine bases you will find in DNA are

  • Adenine
  • Guanine

 

Pyrimidines have a single …….sided ring structure.

 

Pyrimidines have a single six sided ring structure.

   Example of Pyrimidines base

 

Uracil is found in RNA.

 The purine NSs  end in 
“-sine”
The pyrimidine NSs end in
“-dine”
To name the NTs:

  • use the NS name
  •  followed by “mono-“, “di-“

NMP means

 

Nucleotide monophosphate

NDP means

 

Nucleotide diphosphate

NTP means

 

Nucleotide triphosphate

Functions of Nucleotides

nEnergy metabolism
nMonomeric units of nucleic acids
nPhysiological mediators
nPrecursor function
nComponents of coenzymes
nActivated intermediates
nAllosteric effectors

 

Nucleotides are  components of coenzymes:

  • Coenzyme A
  •  FAD
  • NAD+
  • NADP+

Nucleotide activate intermediates like:

  • SAM (AdoMet)
  •  CDP-choline (phospholipids)

Why is purine salvage pathway of metabolism of purine  important?

  • Because free purines are somewhat toxic.

The salvage pathway decreases the levels of PRPP, and therefore decreases the rate 

  • The salvage pathway decreases the levels of PRPP, and therefore decreases the rate 

of purine synthesis. This is an important regulatory mechanism for purine metabolism.

Synthesis of purines requires

 

nAmino acids
¨Glycine
¨Glutamine (2)
¨Aspartate
nCO2   
nOne carbon units transferred via THF (2)

GOUT is a disorder characterized by:
high levels of uric acid in blood, as a result of either the overproduction or under excretion of uric acid.

 

nGout is treated with drug such as

allopurinol  that inhibit xanthineoxidase
CPS I has:

  • Mitochondria
  • Urea Cycle
  • Ammonia
  • Activator:N-acetyl-glutamate

 

              CPS II

 Cytosol

Pyrimidine Synthesis
g-amide group of glutamine
Activator:ATP
Inhibitor:UTP

Source of carbon and nitrogen on pyrimidines are

  • 1,4,5,6 from ASparate
  • 2 from HCO3-
  • 3 from Glutamine amide

Source of carbon and nitrogen atoms in purine ring

1 from Asparate amine

2 from C1-H4folate

3 from Glutamine amide

4, 5,7 from Glycine

8 from C1 H4folate

9 from Glutamine amide 

 

In de novo synthesis, the pyrimidine ring is synthesized from

  • bicarbonate
  • aspartate
  • glutamine (or ammonium ion).

Synthesis of pyrimidines vs. purines.

nFirst, the ring structure is assembled as a free base in pyrimidines, not built upon PRPP like purines.

nSecond, there is no branch in the pyrimidine synthesis pathway.

 

In Synthesis of Pyrimidine Nucleotides, what is regulated step?

 Carbamoyl phosphate

   Synthetase II

 

 

In Synthesis of Pyrimidine Nucleotides, committed step involves which enzyme?

Carbamoylaspartate

The regulatory step in  Synthesis of Pyrimidine

Nucleotides involves which enzyme?

  • Carbamoyl phosphate
  • aspartate

Regulation of Purine Synthesis

Inactivate Purine + PRPP—-> Active Purine

Activate Purine + IMP/GMP/IMP—> Inactivate Purine

Inactivate Purine + ????—-> Active Purine

 

PRPP
Activate Purine +????—> Inactivate Purine
 IMP/GMP/IMP
Metabolism of Purine Nucleotides include:

 

nSynthesis of purine nucleotides
nPurine salvage
nPurine nucleotide interconversions
nGTP and tetrahydobiopterin
nUric acid

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