alexa Uridine and cytidine metabolism following inhibition of de novo pyrimidine synthesis by pyrazofurin.
Chemistry

Chemistry

Medicinal Chemistry

Author(s): Cadman E, Benz C

Abstract Share this page

Abstract Pyrazofurin, an inhibitor of orotidylate decarboxylase, imposes an absolute nutritional requirement for exogenous uridine to maintain normal growth of L5178Y, P388, L1210, W256 and S180 cells in vitro. The amount of uridine necessary for cell division when de novo uridine nucleotide synthesis is inhibited by pyrazofurin is: L5178Y, 30.5; P388, 39.7; L1210, 53.3: W256, 70.6; and S180, 886 fmol/cell. Cytidine, which can be deaminated to uridine, will substitute for uridine to maintain normal cell growth in the presence of growth-inhibitory concentrations of pyrazofurin (5 microM). The requirements for cytidine and uridine are identical. If cytidine deamination is prevented by tetrahydrouridine (100 microM), cytidine can no longer support growth in the presence of pyrazofurin. Cytidine and uridine, as expected, are additive in their effect to permit normal growth of pyrazofurin treated cells. Tetrahydrouridine does not alter this additive effect, indicating that when both nucleotides are added to pyrazofurin treated cells each nucleotide replenishes their respective nucleotide pools and cytidine deamination is unnecessary to allow cell growth. Incorporation of [14C]uridine into the acid insoluble cell fraction of L5178Y cells was 25 fmol/cell at 48 h and remained constant during the remaining growth of the pyrazofurin treated cell suspension. The [14C]uridine acid soluble pool of 4 fmol/cell also was maximum at 48 h but declined during the subsequent growth of the suspension culture to approx. 2 fmol/cell at 96 h. This decline in the acid soluble pool is correlated with a 42\% decrease in modal cell volume during this phase of cell growth which would maintain a constant specific activity of uridine in this pool. This may explain the decline in the acid soluble pool while the acid insoluble pool remains constant during growth of suspension cultures of L51878Y cells. The block in pyrimidine synthesis de novo induced by pyrazofurin provides a useful and quick method for the evaluation of uridine and cytidine metabolism of tumor cell specimens.
This article was published in Biochim Biophys Acta and referenced in Medicinal Chemistry

Relevant Expert PPTs

Relevant Speaker PPTs

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords