FIGURE 7.
Cysteine possible direct and indirect roles in ATP synthesis and in carbon metabolism reprogramming under hypoxia in ovarian cancer cells. (A) Under hypoxia, cysteine degradation could contribute directly to ATP production via not only H2S generation, but also via pyruvate and α-ketobutyrate that could further supply the TCA cycle, leading to increased ATP synthesis. Cysteine could also present an indirect role in ATP synthesis mediated by increasing GSH content under hypoxia, hence counteracting oxidative stress and thereby increasing cellular metabolism. Cystine can also be converted into cysteine persulfide (CysSSH) by CSE and CBS in the cytoplasm or by CSE, CBS and CARS2 in the mitochondria. (B) The axis cysteine-pyruvate-glucose is central in whole metabolic network of carbon. Cysteine degradation can originate pyruvate and glutamate. Pyruvate besides being a major supplier of tricarboxylic acids (TCA) cycle, it can be converted into valine, isoleucine, leucine, alanine, lactate, and acetate. Alanine can be a source of glucose through gluconeogenesis. Glycolysis produce intermediates to supply the TCA cycle (a hub for many precursors of organic compounds, such as threonine) and the pentose phosphate pathway (PPP). PPP intermediates can be converted into amino acids such as histidine and can be conjugated with glycolysis intermediates, originating tyrosine, phenylalanine and serine, which can be converted into glycine. PPP is also crucial in the nucleotide’s synthesis. Acetyl-CoA is a central organic compound in metabolism, when cysteine-derived it proves that cysteine is a valuable supplier of TCA cycle and amino acids and fatty acids syntheses. The increased concentration of these compounds under hypoxia, suggests that cysteine is pushing the metabolic flow in order to supply the main carbon metabolic pathways. The direct incorporation of cysteine into these compounds is possible, however, further studies are needed to clarify this. Based on information from www.bioinfo.org.cn.