Reprogramming of urea cycle in cancer: Mechanism, regulation and prospective therapeutic scopes

Hepatic urea cycle, previously known as ornithine cycle, is the chief biochemical pathway that deals with the disposal of excessive nitrogen in form of urea, resulted from protein breakdown and concomitant condensation of ammonia. Enzymes involved in urea cycle are expressed differentially outside hepatic tissue and are mostly involved in production of arginine from citrulline in arginine-depleted condition. Inline, cancer cells frequently adapt metabolic rewiring to support sufficient biomass production in order to sustain tumor cell survival, multiplication and subsequent growth. For the accomplishment of this aim, metabolic reprogramming in cancer cells is set in way so that cellular nitrogen and carbon repertoire can be utilized and channelized maximally towards anabolic reactions. A strategy to meet such outcome is to cut down unnecessary catabolic reactions and nitrogen elimination. Thus, transfigured urea cycle is a hallmark of neoplasia. During oncogenesis, altered expression and regulation of enzymes involved in urea cycle is a revolutionary approach meet to maximum incorporation of nitrogen for sustaining tumor specific biogenesis. Currently, we have reviewed neoplasm-specific deregulations of urea cycle-enzymes in different types and stages of cancers suggesting its context-oriented dynamic nature. Considering such insight to be valuable in terms of prospective cancer diagnosis and therapeutics adaptive evolution of deregulated urea cycle has been enlightened.