A study of energy metabolism in neoplastic cells

Thesis

Some aspects of substrate utilisation by cultured human and rat cells have been investigated.This was achieved by the measurement of maximal enzyme activities and comparison with rates of flux of substrate to products.Substrates examined in detail include glucose, pyruvate and glutamine with reference to the pathways of glycolysis, glutaminolysis and the Tricarboxylic acid cycle.

A range of cultured cells was examined including examples of untransformed, primary tumorigenic, metastatic and the malignant and suppressed counterparts of hybrid pairs.Some neoplastic cell-lines originated in tumours resulting from carcinogenesis in vivo, others from spontaneous transformation in vitro and others from a process of somatic cell hybridisation.Metabolic characteristics were compared in these various cell-types.

As a result of this metabolic analysis, certain characteristics which are proportional to malignancy over the whole range of cell-lines have been identified.These are distinct from characteristics which have been termed "progression-linked", that is, proportional to malignancy only among cell-lines related in their origins.

A new role is proposed for hexokinase in the regulation of glycolysis in neoplastic cells and this enzyme may be more important than phosphofructokinase in determining the rate of flux of glucose through glycolysis.Additionally, a high-Km glucose-phosphorylating activity, distinct from the low-JG~ hexokinase, was found to be present in many of the tumorigenic cell-lines studied.

It oxaloacetate, Tricarboxylic the provision is proposed that cycling of pyruvate with at a high rate by comparison with that of the acid Cycle, generates branch-point sensitivity for of aspartate for biosynthesis in neoplastic cells.

Authors: Board, M

• Publication date: 1990
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Subjects: Cancer cells; Cell metabolism