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WordNet

a colorless crystalline organic base containing nitrogen; the parent compound of various biologically important substances
any of several bases that are derivatives of purine
production of a chemical compound by a living organism (同)biogenesis

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/04/26 01:30:41」(JST)

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Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

Biosynthesis

The synthesis of IMP.

The color scheme is as follows: enzymes, coenzymes, substrate names, metal ions, inorganic molecules

Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to ribose 5-phosphate. A key regulatory step is the production of 5-phospho-α-D-ribosyl 1-pyrophosphate (PRPP) by PRPP synthetase, which is activated by inorganic phosphate and inactivated by purine ribonucleotides. It is not the committed step to purine synthesis because PRPP is also used in pyrimidine synthesis and salvage pathways. The first committed step is the reaction of PRPP, glutamine and water to 5'-phosphoribosylamine, glutamate, and pyrophosphate - catalyzed by pyrophosphate amidotransferase, which is activated by PRPP and inhibited by AMP, GMP and IMP.

Both adenine and guanine are derived from the nucleotide inosine monophosphate (IMP), which is the first compound in the pathway to have a completely formed purine ring system.

Inosine monophosphate is synthesized on a pre-existing ribose-phosphate through a complex pathway (as shown in the figure on the right). The source of the carbon and nitrogen atoms of the purine ring, 5 and 4 respectively, come from multiple sources. The amino acid glycine contributes all its carbon (2) and nitrogen (1) atoms, with additional nitrogen atoms from glutamine (2) and aspartic acid (1), and additional carbon atoms from formyl groups (2), which are transferred from the coenzyme tetrahydrofolate as 10-formyltetrahydrofolate, and a carbon atom from bicarbonate (1). Formyl groups build carbon-2 and carbon-8 in the purine ring system, which are the ones acting as bridges between two nitrogen atoms.

GMP

IMP dehydrogenase converts IMP into XMP
GMP synthase converts XMP into GMP
GMP reductase converts GMP back into IMP
GMP reductase converts IMP

AMP

adenylosuccinate synthase converts IMP to adenylosuccinate
adenylosuccinate lyase converts adenylosuccinate into AMP
AMP deaminase converts AMP back into IMP

Degradation

Purines are metabolised by several enzymes:

Guanine

A nuclease frees the nucleotide
A nucleotidase creates guanosine
Purine nucleoside phosphorylase converts guanosine to guanine
Guanase converts guanine to xanthine
Xanthine oxidase (a form of xanthine oxidoreductase) catalyzes the oxidation of xanthine to uric acid

Adenine

A nuclease frees the nucleotide
- A nucleotidase creates adenosine, then adenosine deaminase creates inosine
- Alternatively, AMP deaminase creates inosinic acid, then a nucleotidase creates inosine
Purine nucleoside phosphorylase acts upon inosine to create hypoxanthine
Xanthine oxidoreductase catalyzes the biotransformation of hypoxanthine to xanthine
Xanthine oxidoreductase acts upon xanthine to create uric acid

Salvage

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

The enzyme adenine phosphoribosyltransferase (APRT) salvages adenine.
The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) salvages guanine and hypoxanthine. (Genetic deficiency of HGPRT causes Lesch-Nyhan syndrome.)

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, 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, an immunosuppressant used in organ transplantation, autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease such as Crohn's disease and ulcerative colitis.

Mycophenolate mofetil is an immunosuppressant drug used to prevent rejection in organ transplantation; it inhibits purine synthesis by blocking inositol monophosphate dehydrogenase. Also Methotrexate indirectly inhibits purine synthesis by blocking the metabolism of folic acid (it is an inhibitor of the Dihydrofolate reductase).

Allopurinol is a drug that 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

The Medical Biochemistry Page
Purine metabolism - Reference pathway
PUMPA: Purine Metabolic Patients’ Association

UpToDate Contents

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1. 先天性代謝異常：分類 inborn errors of metabolism classification

English Journal

Metabolomics study of intervention effects of Wen-Xin-Formula using ultra high-performance liquid chromatography/mass spectrometry coupled with pattern recognition approach.

Wang X, Wang Q, Zhang A, Zhang F, Zhang H, Sun H, Cao H, Zhang H.SourceNational TCM Key Lab of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, and Key Pharmacometabolomics Platform of Chinese Medicines, Heping Road 24, Harbin 150040, China. Electronic address: pharresearch@hotmail.com.
Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2013 Feb 23;74:22-30. doi: 10.1016/j.jpba.2012.10.009. Epub 2012 Oct 16.
Metabolomics is a new approach based on the systematic study of the full complement of small molecular metabolites in a biological sample. It could map the perturbations of early biochemical changes on diseases and hence provides an opportunity to develop predictive biomarkers that can result in ear
PMID 23245229

Does uric acid qualify as an independent risk factor for cardiovascular mortality?

Jeemon P, Prabhakaran D.AbstractUA (uric acid) is the final product of purine metabolism in humans and is implicated in many disease conditions. Sustained hyperuricaemia has putative adverse roles in cardiovascular diseases. Despite strong evidence emerging from large epidemiological studies supporting the hypothesis that UA independently influences cardiovascular disease outcomes and mortality, a causal role is yet to be established. Serum UA is also considered as a useful biomarker for mortality in high-risk patients with acute coronary syndromes, heart failure and hypertension and in patients with Type 2 diabetes mellitus. Post-hoc analyses of clinical trial data suggest beneficial effects of reducing serum UA. However, these findings are inconclusive and are only hypothesis-generating. In the present issue of Clinical Science, Ndrepepa and co-workers have investigated the prognostic role of UA in high-risk Type 2 diabetic patients with established coronary artery disease in predicting 1-year survival and cardiovascular mortality. These results support the independent role of serum UA in predicting survival in Type 2 diabetic patients. However, long-term follow-up studies are required with serial UA measurement to establish the time-dependent association of UA with mortality outcomes.
Clinical science (London, England : 1979).Clin Sci (Lond).2013 Feb;124(4):255-7. doi: 10.1042/CS20120524.
UA (uric acid) is the final product of purine metabolism in humans and is implicated in many disease conditions. Sustained hyperuricaemia has putative adverse roles in cardiovascular diseases. Despite strong evidence emerging from large epidemiological studies supporting the hypothesis that UA indep
PMID 23043434

Japanese Journal

Alkaloid transporters in plants

Shitan Nobukazu,Kato Keita,Shoji Tsubasa
Plant Biotechnology, 453-463, 2014
… Indeed, molecular and cellular approaches have identified alkaloid transporters of the ATP-binding cassette (ABC) protein, multidrug and toxic compound extrusion (MATE), and purine permease (PUP) families. … Interestingly, some of these transporters were found to be required for the efficient biosynthesis of alkaloids in plants. …
NAID 130004713026

Arabidopsis xanthine dehydrogenase mutants defective in purine degradation show a compromised protective response to drought and oxidative stress

Watanabe Shunsuke,Kounosu Yuka,Shimada Hiroshi,Sakamoto Atsushi
Plant Biotechnology 31(2), 173-178, 2014
… Although generally recognized for its role in nitrogen recycling and remobilization, purine catabolism might also be involved in the plant response and adaptation to environmental stress. … Previously, we demonstrated that allantoin, a major purine intermediary metabolite in stressed plants, stimulates abscisic acid production and activates stress-responsive gene expression, leading to increased tolerance to abiotic stress in Arabidopsis seedlings. …
NAID 130003391372

Uptake of AMP, ADP, and ATP in Escherichia coli W

Watanabe Kimiko,Tomioka Satsuki,Tanimura Kiyoko [他],OKU Hisae,ISOI Koichiro
Bioscience, biotechnology, and biochemistry 75(1), 7-12, 2011-01-23
… purine biosynthesis at a point between IMP and 5-aminoimidazole-4-carboxiamide-1-β-D-ribofuranoside (AICAR), was 1:0.43:0.19. … About 2-fold more radioactive purine bases than purine nucleosides were detected in the cytoplasm after 5 min in an experiment with [8-<SUP>14</SUP>C]AMP and T-1 cells. …
NAID 10027896383