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Studies on the Importance of Serine Metabolism for Purine Synthesis De Novo in a Tumour Cell Line.

Bolton, Mc. (1992) Studies on the Importance of Serine Metabolism for Purine Synthesis De Novo in a Tumour Cell Line. Doctoral thesis, University of Surrey (United Kingdom)..

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Abstract

The transport of serine and the activity of serine hydroxymethyltransferase (SHMT) have been investigated in relation to the supply of one-carbon units for purine synthesis in MOLT-4 cells, a lymphoblastic leukaemia cell line. Serine transport into these cells, in the absence of other amino acids, involved systems A, ASC and L; in the presence of other amino acids, influx by system L was lost. Total serine transport did not have any control on purine synthesis de novo at the normal medium serine concentration of 0. 25mM as determined by metabolic control analysis. Furthermore, the serine efflux rate was the same as the influx rate, which implicates an endogenous source of serine to satisfy the metabolic requirements for this amino acid. The possibility for an endogenous source of serine, or for an alternative source of one-carbon units, for purine synthesis, was substantiated upon observation of a lower rate of incorporation of radiolabel from [3-14C]serine into purine than from [14C]NaHCO3. Neither extracellular glycine, tryptophan, histidine, leucovorin or glucose, nor constituents of serum, contributed significantly to the one-carbon pool. Treatment of cells with 3-fluoro-D-alanine, an inhibitor of SHMT, resulted in a stimulation of incorporation of radiolabel from [3-14C]serine into purine, principally into adenine. This stimulation resulted from an increase in the actual rate of purine synthesis de novo (rather than from an isotope dilution effect) and could not be explained by inhibition of SHMT. Growth phase-related changes in purine synthesis de novo were observed in the absence of changes in the activity of SHMT. The regulation of purine synthesis in these cells is therefore not accomplished through regulation of the expression of SHMT. The possible involvement of mitochondrial SHMT in the supply of one-carbon units for purine synthesis has been discussed in relation to the quantification of serine metabolism as measured In this thesis. In respect of this possibility, it was interesting that 90% of the total SHMT activity was localized in the mitochondria in MOLT-4 cells.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Bolton, Mc.
Date : 1992
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1992.
Depositing User : EPrints Services
Date Deposited : 24 Apr 2020 15:27
Last Modified : 24 Apr 2020 15:27
URI: http://epubs.surrey.ac.uk/id/eprint/854902

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