Human cutaneous melanoma expresses a significant phosphate-dependent glutaminase activity: a comparison with the surrounding skin of the same patient.
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.
Zacharias
Darwin Pinheiro Machado
DP
Federal University of São Paulo (UNIFESP), Brazil.
Lima
Manuela Maria Ramos
MM
Souza
Alcione Lescano
AL
de Abranches Oliveira Santos
Ivan Dunshee
ID
Enokiara
Milvia
M
Michalany
Nilceo
N
Curi
Rui
R
D005972:Glutaminase / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology
D005972:Glutaminase