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Purine metabolism

 

 
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Purine metabolism
 
 
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Many organisms have metabolic pathway
Metabolic pathway

In biochemistry, a metabolic pathway is a series of chemistry reactions occurring within a cell . In each pathway, a principal chemical is modified by chemical reactions....
s to synthesize and break down purine
Purine

Purine is a heterocyclic compound aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
s.

nes are biologically synthesized as nucleotide
Nucleotide

Nucleotides are molecules that comprise the structural units of RNA and DNA. Additionally, nucleotides play central roles in metabolism. In that capacity, they serve as sources of chemical energy , participate in cell signaling , and are incorporated into important cofactors of enzymatic reactions ....
s (bases attached to ribose 5-phosphate
Ribose 5-phosphate

Ribose 5-phosphate is both a product and an intermediate of the pentose phosphate pathway. The last step of the oxidative reactions in the pentose phosphate pathway is the production of ribulose-5-phosphate....
). The committed step is amidophosphoribosyltransferase
Amidophosphoribosyltransferase

Amidophosphoribosyltransferase is an enzyme which converts phosphoribosylpyrophosphate into 5-phosphoribosylamine. The enzyme uses the ammonia group from the glutamine side chain....
.

Both adenine
Adenine

Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactor s nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and Protein biosynthesis, as a chemical component of DNA and RNA....
 and guanine
Guanine

Guanine is one of the five main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, thymine, and uracil. In DNA, guanine is paired with cytosine....
 are derived from the nucleotide inosine monophosphate (IMP), which is synthesised on a pre-existing ribose-phosphate through a complex pathway using atoms from the amino acids glycine
Glycine

Glycine is the organic compound with the chemical formula NH2CH2COOH. It is the smallest of the 20 amino acids commonly found in proteins, coded by codons GGU, GGC, GGA and GGG....
, glutamine
Glutamine

Glutamine is one of the 20 amino acids encoded by the standard genetic code. Its side chain is an amide formed by replacing the side-chain hydroxyl of glutamic acid with an amine functional group....
, and aspartic acid
Aspartic acid

Aspartic acid is an a-amino acid with the chemical formula HO2CCHCH2CO2H. The carboxylate anion of aspartic acid is known as aspartate....
, as well as formate
Formate

Formate or methanoate is the ion CHOO− or HCOO− . It is the simplest carboxylate anion.A formate is a salt or ester of formic acid....
 ions transferred from the coenzyme
Coenzyme

Many enzymes require a cofactor for catalytic activity, accelerating the transformation of a specific substrate to a particular product. The inactive protein, without the cofactor is called an apoenzyme, while the complete enzyme with cofactor is the holoenzyme....
 tetrahydrofolate
Folic acid

Folic acid and Folate are forms of the water-soluble B vitamins. Vitamin B9 is essential to numerous bodily functions ranging from nucleotide synthesis to the remethylation of homocysteine....
.



nes are metabolised by several enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
s:



nes from turnover of nucleic acids (or from food) can also be salvaged and reused in new nucleotides.



a defective gene causes gaps to appear in the metabolic recycling process for purines and pyrimidines, these chemicals are not metabolised properly, and adults or children can suffer from any one of twenty-eight hereditary disorders, possibly some more as yet unknown.






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Encyclopedia


Many organisms have metabolic pathway
Metabolic pathway

In biochemistry, a metabolic pathway is a series of chemistry reactions occurring within a cell . In each pathway, a principal chemical is modified by chemical reactions....
s to synthesize and break down purine
Purine

Purine is a heterocyclic compound aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
s.

Synthesis

Purines are biologically synthesized as nucleotide
Nucleotide

Nucleotides are molecules that comprise the structural units of RNA and DNA. Additionally, nucleotides play central roles in metabolism. In that capacity, they serve as sources of chemical energy , participate in cell signaling , and are incorporated into important cofactors of enzymatic reactions ....
s (bases attached to ribose 5-phosphate
Ribose 5-phosphate

Ribose 5-phosphate is both a product and an intermediate of the pentose phosphate pathway. The last step of the oxidative reactions in the pentose phosphate pathway is the production of ribulose-5-phosphate....
). The committed step is amidophosphoribosyltransferase
Amidophosphoribosyltransferase

Amidophosphoribosyltransferase is an enzyme which converts phosphoribosylpyrophosphate into 5-phosphoribosylamine. The enzyme uses the ammonia group from the glutamine side chain....
.

Both adenine
Adenine

Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactor s nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and Protein biosynthesis, as a chemical component of DNA and RNA....
 and guanine
Guanine

Guanine is one of the five main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, thymine, and uracil. In DNA, guanine is paired with cytosine....
 are derived from the nucleotide inosine monophosphate (IMP), which is synthesised on a pre-existing ribose-phosphate through a complex pathway using atoms from the amino acids glycine
Glycine

Glycine is the organic compound with the chemical formula NH2CH2COOH. It is the smallest of the 20 amino acids commonly found in proteins, coded by codons GGU, GGC, GGA and GGG....
, glutamine
Glutamine

Glutamine is one of the 20 amino acids encoded by the standard genetic code. Its side chain is an amide formed by replacing the side-chain hydroxyl of glutamic acid with an amine functional group....
, and aspartic acid
Aspartic acid

Aspartic acid is an a-amino acid with the chemical formula HO2CCHCH2CO2H. The carboxylate anion of aspartic acid is known as aspartate....
, as well as formate
Formate

Formate or methanoate is the ion CHOO− or HCOO− . It is the simplest carboxylate anion.A formate is a salt or ester of formic acid....
 ions transferred from the coenzyme
Coenzyme

Many enzymes require a cofactor for catalytic activity, accelerating the transformation of a specific substrate to a particular product. The inactive protein, without the cofactor is called an apoenzyme, while the complete enzyme with cofactor is the holoenzyme....
 tetrahydrofolate
Folic acid

Folic acid and Folate are forms of the water-soluble B vitamins. Vitamin B9 is essential to numerous bodily functions ranging from nucleotide synthesis to the remethylation of homocysteine....
.

GMP

  • IMP dehydrogenase
    IMP dehydrogenase

    IMP dehydrogenase is an enzyme which converts inosine monophosphate to xanthosine monophosphate....
     converts IMP into XMP
    Xanthosine monophosphate

    Xanthosine monophosphate is an intermediate in purine metabolism, formed from Inosine monophosphate, and forming Guanosine monophosphate....
  • GMP synthase
    GMP synthase

    Guanine monphosphate synthetase, also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate....
     converts XMP into GMP
  • GMP reductase
    GMP reductase

    GMP reductase is an enzyme which converts Guanosine monophosphate to Inosine monophosphate. In melanocytic cells GMP reductase gene expression may be regulated by Microphthalmia-associated transcription factor....
     converts GMP back into IMP


AMP

  • adenylosuccinate synthase
    Adenylosuccinate synthase

    Adenylosuccinate synthase is an enzyme which converts Inosine monophosphate to adenylosuccinate.External links...
     converts IMP to adenylosuccinate
    Adenylosuccinate

    Adenylosuccinate is an intermediate in purine metabolism.It is formed from inosine monophosphate by adenylosuccinate synthase....
  • adenylosuccinate lyase
    Adenylosuccinate lyase

    Adenylosuccinate lyase is an enzyme which converts adenylosuccinate to Adenosine monophosphate and fumarate.See also* Purine metabolism...
     converts adenylosuccinate into AMP
    Adenosine monophosphate

    Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is found in RNA. It is an ester of phosphoric acid and the nucleoside adenosine....
  • AMP deaminase
    AMP deaminase

    Adenosine monophosphate deaminase 1 , also known as AMPD1, is a human gene.Myoadenylate deaminase, also called AMP deaminase, is an enzyme that converts adenosine monophosphate to inosine monophosphate , freeing an ammonia molecule in the process....
     converts AMP back into IMP


Degradation

Purines are metabolised by several enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
s:

Guanine

  • A nuclease
    Nuclease

    A nuclease is an enzyme capable of cleaving the phosphodiester bonds between the nucleotide subunits of nucleic acids. Older papers may use terms such as "polynucleotidase" or "nucleodepolymerase"....
     frees the nucleotide
    Nucleotide

    Nucleotides are molecules that comprise the structural units of RNA and DNA. Additionally, nucleotides play central roles in metabolism. In that capacity, they serve as sources of chemical energy , participate in cell signaling , and are incorporated into important cofactors of enzymatic reactions ....
  • A nucleotidase
    Nucleotidase

    A nucleotidase is a hydrolase that catalyzes the hydrolysis of a nucleotide into a nucleoside and a phosphate. For example, they convert adenosine monophosphate to adenosine, and guanosine monophosphate to guanosine....
     creates guanosine
    Guanosine

    Guanosine is a nucleoside comprising guanine attached to a ribose ring via a ?-N9-glycosidic bond.Guanosine can be phosphorylated to become GMP , cGMP , GDP and GTP ....
  • Purine nucleoside phosphorylase
    Purine nucleoside phosphorylase

    Purine nucleoside phosphorylase is an enzyme involved in Purine#Metabolism. PNP metabolizes adenosine into adenine, inosine into hypoxanthine, and guanosine into guanine, in each case creating ribose phosphate....
     converts guanosine
    Guanosine

    Guanosine is a nucleoside comprising guanine attached to a ribose ring via a ?-N9-glycosidic bond.Guanosine can be phosphorylated to become GMP , cGMP , GDP and GTP ....
     to guanine
    Guanine

    Guanine is one of the five main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, thymine, and uracil. In DNA, guanine is paired with cytosine....
  • Guanase converts guanine to xanthine
    Xanthine

    Xanthine , , is a purine base found in most body tissues and fluids and in other organisms. A number of mild stimulants are derived from xanthine, including caffeine and theobromine....
  • Xanthine oxidase
    Xanthine oxidase

    The enzyme xanthine oxidase, or XO, catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid....
     converts xanthine to uric acid
    Uric acid

    Uric acid is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3....


Adenine

  • A nuclease
    Nuclease

    A nuclease is an enzyme capable of cleaving the phosphodiester bonds between the nucleotide subunits of nucleic acids. Older papers may use terms such as "polynucleotidase" or "nucleodepolymerase"....
     frees the nucleotide
    Nucleotide

    Nucleotides are molecules that comprise the structural units of RNA and DNA. Additionally, nucleotides play central roles in metabolism. In that capacity, they serve as sources of chemical energy , participate in cell signaling , and are incorporated into important cofactors of enzymatic reactions ....
    • A nucleotidase
      Nucleotidase

      A nucleotidase is a hydrolase that catalyzes the hydrolysis of a nucleotide into a nucleoside and a phosphate. For example, they convert adenosine monophosphate to adenosine, and guanosine monophosphate to guanosine....
       creates adenosine
      Adenosine

      Adenosine is a nucleoside composed of a molecule of adenine attached to a ribose sugar molecule moiety via a ?-N9-glycosidic bond....
      , then adenosine deaminase
      Adenosine deaminase

      Adenosine deaminase is an enzyme involved in Purine#Metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues....
       creates inosine
      Inosine

      Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring via a ?-N9-glycosidic bond.Inosine is commonly found in tRNAs and is essential for proper translation of the genetic code in wobble base pairs....
    • Alternatively, AMP deaminase
      AMP deaminase

      Adenosine monophosphate deaminase 1 , also known as AMPD1, is a human gene.Myoadenylate deaminase, also called AMP deaminase, is an enzyme that converts adenosine monophosphate to inosine monophosphate , freeing an ammonia molecule in the process....
       creates inosinic acid
      Inosinic acid

      Inosinic acid or inosine monophosphate is a nucleotide, specifically a nucleoside monophosphate. Inosinic acid is important in metabolism....
      , then a nucleotidase
      Nucleotidase

      A nucleotidase is a hydrolase that catalyzes the hydrolysis of a nucleotide into a nucleoside and a phosphate. For example, they convert adenosine monophosphate to adenosine, and guanosine monophosphate to guanosine....
       creates inosine
      Inosine

      Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring via a ?-N9-glycosidic bond.Inosine is commonly found in tRNAs and is essential for proper translation of the genetic code in wobble base pairs....
  • Purine nucleoside phosphorylase
    Purine nucleoside phosphorylase

    Purine nucleoside phosphorylase is an enzyme involved in Purine#Metabolism. PNP metabolizes adenosine into adenine, inosine into hypoxanthine, and guanosine into guanine, in each case creating ribose phosphate....
     acts upon inosine to create hypoxanthine
    Hypoxanthine

    Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids where it is present in the anticodon of tRNA in the form of its nucleoside inosine....
  • Xanthine oxidoreductase acts upon hypoxanthine to create xanthine
    Xanthine

    Xanthine , , is a purine base found in most body tissues and fluids and in other organisms. A number of mild stimulants are derived from xanthine, including caffeine and theobromine....
  • Xanthine oxidoreductase acts upon xanthine to create uric acid
    Uric acid

    Uric acid is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3....


Salvage

Purines from turnover of nucleic acids (or from food) can also be salvaged and reused in new nucleotides.

  • The enzyme adenine phosphoribosyltransferase
    Adenine phosphoribosyltransferase

    Adenine phosphoribosyltransferase, also known as APRT, is a human gene.The protein encoded by this gene, APRTase is an enzyme involved in the purine nucleotide salvage pathway....
     (APRT) salvages adenine
    Adenine

    Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactor s nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and Protein biosynthesis, as a chemical component of DNA and RNA....
    .
  • The enzyme hypoxanthine-guanine phosphoribosyltransferase
    Hypoxanthine-guanine phosphoribosyltransferase

    Hypoxanthine-guanine phosphoribosyltransferase is an enzyme in purine metabolism....
     (HGPRT) salvages guanine
    Guanine

    Guanine is one of the five main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, thymine, and uracil. In DNA, guanine is paired with cytosine....
     and hypoxanthine
    Hypoxanthine

    Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids where it is present in the anticodon of tRNA in the form of its nucleoside inosine....
    . (Genetic deficiency of HGPRT causes Lesch-Nyhan syndrome
    Lesch-Nyhan syndrome

    Lesch-Nyhan syndrome , also known as Nyhan?s syndrome or Kelley-Seegmiller syndrome, is a rare, inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase , produced by mutations in the HPRT gene....
    .)


Disorders

When a defective gene causes gaps to appear in the metabolic recycling process for purines and pyrimidines, these chemicals are not metabolised properly, and adults or children can suffer from any one of twenty-eight hereditary disorders, possibly some more as yet unknown. Symptoms can include gout, anaemia, autism, epilepsy, delayed development, deafness, compulsive self-biting, kidney failure or stones, or loss of immunity.

Pharmacotherapy

Modulation of purine metabolism has pharmacotherapeutic value.

Purine synthesis inhibitors inhibit the proliferation of cells, especially leukocytes. These inhibitors include azathioprine
Azathioprine

Azathioprine is an immunosuppressant used in organ transplantation, autoimmune disease such as rheumatoid arthritis and pemphigus or inflammatory bowel disease such as Crohn's disease and ulcerative colitis as well as multiple sclerosis....
, an immunosupressant used in organ transplant
Organ transplant

Organ transplant is the moving of an organ from one body to another , for the purpose of replacing the recipient's damaged or failing organ with a working one from the donor site....
ation, autoimmune disease
Autoimmune disease

Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body attacks its own cells....
 such as rheumatoid arthritis
Rheumatoid arthritis

Rheumatoid arthritis is a chronic, systemic disease inflammation that may affect many tissues and organs, but principally attacks the joints producing a inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints....
 or inflammatory bowel disease such as Crohn's disease
Crohn's disease

Crohn's disease is an inflammatory disease which may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms....
 and ulcerative colitis
Ulcerative colitis

Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the intestine, specifically the large intestine or colon , that includes characteristic Peptic ulcer, or open sores, in the colon....
.

Allopurinol is a drug which inhibits the enzyme xanthine oxidoreductase and thus lowers the level of uric acid in the body. This may be useful in the treatment of gout, which is a disease caused by excess uric acid forming crystals in joints.

External links