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Human cutaneous melanoma expresses a significant phosphate-dependent glutaminase activity: a comparison with the surrounding skin of the same patient
Authors:Zacharias Darwin Pinheiro Machado  Lima Manuela Maria Ramos  Souza Alcione Lescano  de Abranches Oliveira Santos Ivan Dunshee  Enokiara Milvia  Michalany Nilceo  Curi Rui
Affiliation:Federal University of S?o Paulo (UNIFESP), Brazil.
Abstract:The protein content and the activity and type of phosphate-dependent glutaminase were determined in freshly pigmented lesions obtained from human melanoma and adjacent skin. Significant phosphate-dependent glutaminase activity was found in both the melanoma and non-pigmented adjacent skin areas. A comparison between the pigmented and adjacent skin areas suggests the occurrence of gradual metabolic changes that result in an increased protein content in the centre of the neoplasia. The presence of a kidney-type glutaminase (K(m) of 2-5 mm) indicates a high sensitivity of the melanoma to variations in glutamine plasma levels (0.6 to 1 mm). These data lead us to postulate that glutamine supply is an important factor for melanoma cell proliferation, being a source of nitrogen for DNA and RNA synthesis. The intense neovascularization observed in melanoma ensures the oxygen supply that is required for glutamine oxidation. These findings support the proposition that glutamine is an important fuel for melanoma.
Keywords:cutaneous melanoma  glutamine  phosphate‐dependent glutaminase activity
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