METABOLISM OF GLUTAMINE IN THE TUMOUR CELL

ABSTRACT

Neoplasms are illnesses with alterations in the DNA, caused by various events. Their origin is monoclonal and, after development and genic instability, new clones appear. Neoplasic attributes (cariotype, invasiveness, antineoplasic susceptibility, growth rate, hormonal susceptibility, metastatic capability) are heterogeneous, demanding high-energy flow, macromolecules and nitrogen. Thus the metabolic ways in these cells give them the premises for the synthesis of structural and regulating lipides, DNA and RNA. A tumorous cell uses any substratum as an energy source: glucose, lipids, cetonic bodies and amino acids, competing with the host for glucose. Glutamine and alanine are two nitrogen and carbon framework carriers in various tissues. Ammonium ion is extremely toxic to cells, having to be carried by amino acid. Therefore glutamine results to be the main nitrogen source for tumorous cells, causing deep changes in the metabolism of the host, through an increasing need of glutamine by the cells. Glycolysis and glutaminolysis are not essential to neoplasms, they are primarily strategic opportunities of survival and proliferation under circumstances of lack of nutrients and oxygen. In tumorous cells the expression of mitochondrial P-dependent glutaminase and mitochondrial Pdependent malato-NAD decaboxylase, enzymes which oxidate pyruvate and acetyl CoA, occurs. Conversion of glutamine into lactate is called glutaminolysis; its function is to produce energy, glutamate, citrate and aspartate. The glutamine concentration is inversely proportional to the neoplasm growth, with an increase of glutaminase and a decrease, dispensable in tumours, of glutamine synthetase. The study of the metabolic ways of tumorous cells provides a support in the struggle against neoplasms. Since tumours also synthesize less amino acids than normal cells (they need to receive supplementary amino acids from the extracellular fluid and carbon) they become vulnerable to a blockage of amino acid carriers, this being the base of a therapy against cancer.

KEY WORDS:
Glutamine; glutaminase; metabolism; neoplasm.