Figure 2.

Silencing of ASS1 occurs in malignant GBMs through HIF-1α activation or epigenetic mechanisms. This functionally inhibits the urea cycle, shunting key metabolic intermediates toward other pathways. The amino acid arginine can be used in the biosynthesis of nitric oxide to support angiogenesis or can be incorporated in polyamines and proteins to support tumor growth. Additionally, the accumulation of aspartate in ASS1-silenced tumors supports the continued synthesis of pyrimidine nucleotides.